The prevalence of tuberculosis infection among foreign-born Canadians: a modelling study.

BACKGROUND: The prevalence of tuberculosis infection is critical to the design of tuberculosis prevention strategies, yet is unknown in Canada. We estimated the prevalence of tuberculosis infection among Canadian residents born abroad. METHODS: We estimated the prevalence of tuberculosis infection by age and year of migration to Canada for people from each of 168 countries by constructing country-specific and calendar year-specific trends for annual risk of infection using a previously developed model. We combined country-specific prevalence estimates with Canadian Census data from 2001, 2006, 2011, 2016 and 2021 to estimate the overall prevalence of tuberculosis infection among foreign-born Canadian residents. RESULTS: The estimated overall prevalence of tuberculosis infection among foreign-born people in Canada was 25% (95% uncertainty interval [UI] 20%-35%) for census year 2001, 24% (95% UI 20%-33%) for 2006, 23% (95% UI 19%-30%) for 2011, 22% (95% UI 19%-28%) for 2016 and 22% (95% UI 19%-27%) for 2021. The prevalence increased with age at migration and incidence of tuberculosis in the country of origin. In 2021, the estimated prevalence of infection among foreign-born residents was lowest in Quebec (19%, 95% UI 16%-24%) and highest in Alberta (24%, 95% UI 21%-28%) and British Columbia (24%, 95% UI 20%-30%). Among all foreign-born Canadian residents with tuberculosis infection in 2021, we estimated that only 1 in 488 (95% UI 185-1039) had become infected within the 2 preceding years. INTERPRETATION: About 1 in 4 foreign-born Canadian residents has tuberculosis infection, but very few were infected within the 2 preceding years (the highest risk period for progression to tuberculosis disease). These data may inform future tuberculosis infection screening policies.

Distinct healthcare utilization profiles of high healthcare use tuberculosis survivors: A latent class analysis.

BACKGROUND: Recent data have demonstrated that healthcare use after treatment for respiratory tuberculosis (TB) remains elevated in the years following treatment completion. However, it remains unclear which TB survivors are high healthcare users and whether any variation exists within this population. Thus, the primary objective of this study was to identify distinct profiles of high healthcare-use TB survivors to help inform post-treatment support and care. METHODS: Using linked health administrative data from British Columbia, Canada, we identified foreign-born individuals who completed treatment for incident respiratory TB between 1990 and 2019. We defined high healthcare-use TB survivors as those in the top 10% of annual emergency department visits, hospital admissions, or general practitioner visits among the study population during the five-year period immediately following TB treatment completion. We then used latent class analysis to categorize the identified high healthcare-use TB survivors into subgroups. RESULTS: Of the 1,240 people who completed treatment for respiratory TB, 258 (20.8%) people were identified as high post- TB healthcare users. Latent class analysis results in a 2-class solution. Class 1 (n = 196; 76.0%) included older individuals (median age 71.0; IQR 59.8, 79.0) with a higher probability of pre-existing hypertension and diabetes (41.3% and 33.2%, respectively). Class 2 (n = 62; 24.0%) comprised of younger individuals (median age 31.0; IQR 27.0, 41.0) with a high probability (61.3%) of immigrating to Canada within five years of their TB diagnosis and a low probability (11.3%) of moderate to high continuity of primary care. DISCUSSION: Our findings suggest that foreign-born high healthcare-use TB survivors in a high-resource setting may be categorized into distinct profiles to help guide the development of person-centred care strategies targeting the long-term health impacts TB survivors face.

Medical Malpractice and the Neurologist: An Introduction.

This article provides an overview of current malpractice trends in neurology as well as non-malpractice and forensic liability concerns. It is more important for clinicians to recognize the common patient care scenarios that are likely to precipitate lawsuits rather than memorize arcane legal principles. Therefore, this article offers an introduction to malpractice jurisprudence as well as a general overview of current litigation trends and a review of the role and duties of a neurologist serving as an expert witness. The next article highlights mitigation strategies for the most prevalent neurologic misadventures.

Medical Malpractice and the Neurologist: Specific Neurological Claims.

This chapter highlights the most frequently encountered neurological malpractice claims. The format is designed to provide a rudimentary understanding of how lawsuits arise and thereby focus discussion on adapting practice patterns to improve patient care and minimize liability risk.

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.

Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study.

RATIONALE & OBJECTIVE: Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A provincial kidney pathology registry (2000-2012) was used to identify 3,079 adult patients with IgA nephropathy, focal segmental glomerulosclerosis (FSGS), antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, or "other" glomerular diseases in British Columbia, Canada. EXPOSURE: Predictors included demographics, immigration status, comorbidities, immunosuppression use, estimated glomerular filtration rate (eGFR), and proteinuria. OUTCOME: A diagnosis of active TB was ascertained using administrative data linkages and defined based on (1) the dispensation of 1 or more unique combinations of medications used to treat active TB, or (2) physician or hospital visits for active TB. ANALYTICAL APPROACH: The definition of TB was validated in an external cohort linked to the Provincial TB registry at the BC Centre for Disease Control (BCCDC). Standardized incidence ratios were calculated using the age-matched general population. Risk factors for active TB were identified using Cox proportional hazards regression analysis. RESULTS: The sensitivity and specificity of the outcome definition of active TB were 87.6% and 99.5%, respectively. During a median follow-up of 6.2 years, 41 patients developed active TB with an incidence of 197 of 100,000 person-years, approximately 23 times as high as the general population and>6 times higher than the threshold of 30 per 100,000 used to define high TB incidence. A high incidence was observed in all glomerular diseases (range, 110-403 per 100,000), in both Canadian- and foreign-born patients (range, 124-424 per 100,000), and in patients exposed or not to immunosuppression (282 vs 147 per 100,000). Factors associated with higher TB risk included immigration from a high-incidence country (HR, 3.90 [95% CI, 1.75-8.68]), diminished eGFR (HR, 2.81 [95% CI, 1.18-6.69]), higher levels of proteinuria (HR, 1.15 [95% CI, 1.04-1.27]), lupus nephritis (HR, 2.79 [95% CI, 1.37-5.68]), and immunosuppression use (HR, 2.13 [95% CI, 1.13-4.03]). LIMITATIONS: A relatively low number of events contributed to uncertainty in risk estimates. CONCLUSIONS: Patients with glomerular disease have a high incidence of active TB irrespective of disease type, demographics, or use of immunosuppression. Prospective studies are needed to evaluate the utility of screening for latent TB infection in this population. PLAIN-LANGUAGE SUMMARY: Patients with kidney failure are at high risk of developing tuberculosis (TB), a major infection that can be prevented by identifying and treating patients who have had prior exposure to TB. The risk of TB in specific kidney diseases is unknown. In this Canadian study of 3,079 patients with glomerular disease, a group of autoimmune kidney conditions, the rate of TB was 23 times higher than in the general population. The rate was high irrespective of the use of immunosuppressive drugs or whether patients had immigrated to Canada from another country. These findings suggest that screening patients with glomerular disease for prior TB exposure may be beneficial; however, this needs to be evaluated in a prospective study.

The association of SARS-CoV-2 infection and tuberculosis disease with unfavorable treatment outcomes: A systematic review.

BACKGROUND: Whether SARS-CoV-2 infection and its management influence tuberculosis (TB) treatment outcomes is uncertain. We synthesized evidence on the association of SARS-CoV-2 coinfection (Coinfection Review) and its management (Clinical Management Review) on treatment outcomes among people with tuberculosis (TB) disease. METHODS: We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable (death, treatment failure, loss-to-follow-up) TB treatment outcomes (Coinfection and Clinical Management Review) and/or severe or critical COVID-19 or death (Clinical Management Review). Study quality was assessed with an adapted Newcastle Ottawa Scale. Data were heterogeneous and a narrative review was performed. An updated search was performed on April 3, 2023. FINDINGS: From 9,529 records, we included 11 studies and 7305 unique participants. No study reported data relevant to our review in their primary publication and data had to be contributed by study authors after contact. Evidence from all studies was low quality. Eight studies of 5749 persons treated for TB (286 [5%] with SARS-CoV-2) were included in the Coinfection Review. Across five studies reporting our primary outcome, there was no significant association between SARS-CoV-2 coinfection and unfavorable TB treatment outcomes. Four studies of 1572 TB patients-of whom 291 (19%) received corticosteroids or other immunomodulating treatment-were included in the Clinical Management Review, and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies. When updating our search, we still did not identify any study reporting data relevant to this review in their primary publication. INTERPRETATION: No study was designed to answer our research questions of interest. It remains unclear whether TB/SARS-CoV-2 and its therapeutic management are associated with unfavorable outcomes. Research is needed to improve our understanding of risk and optimal management of persons with TB and SARS-CoV-2 infection. TRIAL REGISTRATION: Registration: PROSPERO (CRD42022309818).

Comparing Mycobacterium tuberculosis transmission reconstruction models from whole genome sequence data.

Genomic epidemiology is routinely used worldwide to interrogate infectious disease dynamics. Multiple computational tools exist that reconstruct transmission networks by coupling genomic data with epidemiological models. Resulting inferences can improve our understanding of pathogen transmission dynamics, and yet the performance of these tools has not been evaluated for tuberculosis (TB), a disease process with complex epidemiology including variable latency and within-host heterogeneity. Here, we performed a systematic comparison of six publicly available transmission reconstruction models, evaluating their accuracy when predicting transmission events in simulated and real-world Mycobacterium tuberculosis outbreaks. We observed variability in the number of transmission links that were predicted with high probability (P ≥ 0.5) and low accuracy of these predictions against known transmission in simulated outbreaks. We also found a low proportion of epidemiologically supported case-contact pairs were identified in our real-world TB clusters. The specificity of all models was high, and a relatively high proportion of the total transmission events predicted by some models were true links, notably with TransPhylo, Outbreaker2, and Phybreak. Our findings may inform the choice of tools in TB transmission analyses and underscore the need for caution when interpreting transmission networks produced using probabilistic approaches.

Risk of Tuberculosis Disease in People With Chronic Kidney Disease Without Kidney Failure: A Systematic Review and Meta-analysis.

BACKGROUND: Kidney failure is an established risk factor for tuberculosis (TB), but little is known about TB risk in people with chronic kidney disease (CKD) who have not initiated kidney replacement therapy (CKD without kidney failure). Our primary objective was to estimate the pooled relative risk of TB disease in people with CKD stages 3-5 without kidney failure compared with people without CKD. Our secondary objectives were to estimate the pooled relative risk of TB disease for all stages of CKD without kidney failure (stages 1-5) and by each CKD stage. METHODS: This review was prospectively registered (PROSPERO CRD42022342499). We systematically searched MEDLINE, Embase, and Cochrane databases for studies published between 1970 and 2022. We included original observational research estimating TB risk among people with CKD without kidney failure. Random-effects meta-analysis was performed to obtain the pooled relative risk. RESULTS: Of the 6915 unique articles identified, data from 5 studies were included. The estimated pooled risk of TB was 57% higher in people with CKD stages 3-5 than in people without CKD (adjusted hazard ratio: 1.57; 95% CI: 1.22-2.03; I2 = 88%). When stratified by CKD stage, the pooled rate of TB was highest in stages 4-5 (incidence rate ratio: 3.63; 95% CI: 2.25-5.86; I2 = 89%). CONCLUSIONS: People with CKD without kidney failure have an increased relative risk of TB. Further research and modeling are required to understand the risks, benefits, and CKD cutoffs for screening people for TB with CKD prior to kidney replacement therapy.

Healthcare Utilization After Respiratory Tuberculosis: A Controlled Interrupted Time Series Analysis.

BACKGROUND: Despite data suggesting elevated morbidity and mortality among people who have survived tuberculosis disease, the impact of respiratory tuberculosis on healthcare utilization in the years following diagnosis and treatment remains unclear. METHODS: Using linked health administrative data from British Columbia, Canada, we identified foreign-born individuals treated for respiratory tuberculosis between 1990 and 2019. We matched each person with up to four people without a tuberculosis diagnosis from the same source cohort using propensity score matching. Then, using a controlled interrupted time series analysis, we measured outpatient physician encounters and inpatient hospital admissions in the 5 years following respiratory tuberculosis diagnosis and treatment. RESULTS: We matched 1216 individuals treated for respiratory tuberculosis to 4864 non-tuberculosis controls. Immediately following the tuberculosis diagnostic and treatment period, the monthly rate of outpatient encounters in the tuberculosis group was 34.0% (95% confidence interval [CI]: 30.7%, 37.2%) higher than expected, and this trend was sustained for the duration of the post-tuberculosis period. The excess utilization represented an additional 12.2 (95% CI: 10.6, 14.9) outpatient encounters per person over the post-tuberculosis period, with respiratory morbidity a large contributor to the excess healthcare utilization. Results were similar for hospital admissions, with an additional 0.4 (95% CI: .3, .5) hospital admissions per person over the post-tuberculosis period. CONCLUSIONS: Respiratory tuberculosis appears to have long-term impacts on healthcare utilization beyond treatment. These findings underscore the need for screening, assessment, and treatment of post-tuberculosis sequelae, as it may provide an opportunity to improve health and reduce resource use.

Role of latent tuberculosis infection on elevated risk of cardiovascular disease: a population-based cohort study of immigrants in British Columbia, Canada, 1985-2019.

We investigated cardiovascular disease (CVD) risk associated with latent tuberculosis infection (LTBI) (Aim-1) and LTBI therapy (Aim-2) in British Columbia, a low-tuberculosis-incidence setting. 49,197 participants had valid LTBI test results. Cox proportional hazards model was fitted, adjusting for potential confounders. Compared with the participants who tested LTBI negative, LTBI positive was associated with an 8% higher CVD risk in complete case data (adjusted hazard ratio (HR): 1.08, 95% CI: 0.99-1.18), a statistically significant 11% higher risk when missing confounder values were imputed using multiple imputation (HR: 1.11, 95% CI: 1.02-1.20), and 10% higher risk when additional proxy variables supplementing known unmeasured confounders were incorporated in the highdimensional disease risk score technique to reduce residual confounding (HR: 1.10, 95% CI: 1.01-1.20). Also, compared with participants who tested negative, CVD risk was 27% higher among people who were LTBI positive but incomplete LTBI therapy (HR: 1.27, 95% CI: 1.04-1.55), whereas the risk was similar in people who completed LTBI therapy (HR: 1.04, 95% CI: 0.87-1.24). Findings were consistent in different sensitivity analyses. We concluded that LTBI is associated with an increased CVD risk in low-tuberculosis-incidence settings, with a higher risk associated with incomplete LTBI therapy and attenuated risk when therapy is completed.

Post-COVID dyspnea: prevalence, predictors, and outcomes in a longitudinal, prospective cohort.

BACKGROUND: The pathophysiology, evolution, and associated outcomes of post-COVID dyspnea remain unknown. The aim of this study was to determine the prevalence, severity, and predictors of dyspnea 12 months following hospitalization for COVID-19, and to describe the respiratory, cardiac, and patient-reported outcomes in patients with post-COVID dyspnea. METHODS: We enrolled a prospective cohort of all adult patients admitted to 2 academic hospitals in Vancouver, Canada with PCR-confirmed SARS-CoV-2 during the first wave of COVID between March and June 2020. Dyspnea was measured 3, 6, and 12 months after initial symptom onset using the University of California San Diego Shortness of Breath Questionnaire. RESULTS: A total of 76 patients were included. Clinically meaningful dyspnea (baseline score > 10 points) was present in 49% of patients at 3 months and 46% at 12 months following COVID-19. Between 3 and 12 months post-COVID-19, 24% patients had a clinically meaningful worsening in their dyspnea, 49% had no meaningful change, and 28% had a clinically meaningful improvement in their dyspnea. There was worse sleep, mood, quality of life, and frailty in patients with clinically meaningful dyspnea at 12 months post-COVID infection compared to patients without dyspnea. There was no difference in PFT findings, troponin, or BNP comparing patients with and without clinically meaningful dyspnea at 12 months. Severity of dyspnea and depressive symptoms at 3 months predicted severity of dyspnea at 12 months. CONCLUSIONS: Post-COVID dyspnea is common, persistent, and negatively impacts quality of life. Mood abnormalities may play a causative role in post-COVID dyspnea in addition to potential cardiorespiratory abnormalities. Dyspnea and depression at initial follow-up predict longer-term post-COVID dyspnea, emphasizing that standardized dyspnea and mood assessment following COVID-19 may identify patients at high risk of post-COVID dyspnea and facilitating early and effective management.

Multimorbidity prevalence and chronic disease patterns among tuberculosis survivors in a high-income setting.

OBJECTIVES: Multimorbidity is the presence of two or more chronic health conditions. Tuberculosis (TB) survivors are known to have higher prevalence of multimorbidity, although prevalence estimates from high-income low-TB incidence jurisdictions are not available and potential differences in the patterns of chronic disease among TB survivors with multimorbidity are poorly understood. In this study, we aimed to (1) compare the prevalence of multimorbidity among TB survivors with matched non-TB controls in a high-income setting; (2) assess the robustness of aim 1 analyses to different modelling strategies, unmeasured confounding, and misclassification bias; and (3) among people with multimorbidity, elucidate chronic disease patterns specific to TB survivors. METHODS: A population-based cohort study of people immigrating to British Columbia, Canada, 1985-2015, using health administrative data. Participants were divided into two groups: people diagnosed with TB (TB survivors) and people not diagnosed with TB (non-TB controls) in British Columbia. Coarsened exact matching (CEM) balanced demographic, immigration, and socioeconomic covariates between TB survivors and matched non-TB controls. Our primary outcome was multimorbidity, defined as ≥2 chronic diseases from the Elixhauser comorbidity index. RESULTS: In the CEM-matched sample (n=1962 TB survivors; n=1962 non-TB controls), we estimated that 21.2% of TB survivors (n=416), compared with 12% of non-TB controls (n=236), had multimorbidity. In our primary analysis, we found a double-adjusted prevalence ratio of 1.74 (95% CI: 1.49-2.05) between TB survivors and matched non-TB controls for multimorbidity. Among people with multimorbidity, differences were observed in chronic disease frequencies between TB survivors and matched controls. CONCLUSION: TB survivors had a 74% higher prevalence of multimorbidity compared with CEM-matched non-TB controls. TB-specific multimorbidity patterns were observed through differences in chronic disease frequencies between the matched samples. These findings suggest a need for TB-specific multimorbidity interventions in high-income settings such as Canada. We suggest TB survivorship as a framework for developing person-centred interventions for multimorbidity among TB survivors.

RéSUMé: OBJECTIFS: La multimorbidité est la présence de deux affections chroniques ou plus. On sait que la prévalence de la multimorbidité est plus élevée chez les survivants de la tuberculose, mais il n'y a pas d'estimations de prévalence disponibles dans les entités administratives à revenu élevé et à faible incidence de tuberculose, et les différences potentielles dans les structures de la morbidité chronique chez les survivants de la tuberculose atteints de multimorbidité sont mal comprises. Dans cette étude, nous avons voulu 1) comparer la prévalence de la multimorbidité chez des survivants de la tuberculose appariés à des témoins sans tuberculose dans un milieu à revenu élevé; 2) évaluer la robustesse des analyses du 1er objectif par rapport à différentes stratégies de modélisation, à la confusion non mesurée et au biais d'erreur de classification; et 3) élucider, chez les personnes atteintes de multimorbidité, les structures de la morbidité chronique propres aux survivants de la tuberculose. MéTHODE: Nous avons mené à l'aide de données administratives sur la santé une étude de cohorte populationnelle des personnes ayant immigré en Colombie-Britannique (Canada) entre 1985 et 2015. Les participants ont été divisés en deux groupes : les personnes ayant un diagnostic de tuberculose (« survivants de la tuberculose ¼) et les personnes n'ayant pas de diagnostic de tuberculose (« témoins sans tuberculose ¼) en Colombie-Britannique. Un appariement exact avec groupement (coarsened exact matching [CEM]) a permis d'équilibrer les covariables démographiques, socioéconomiques et d'immigration entre les survivants de la tuberculose et les témoins sans tuberculose appariés. Notre principal résultat a été la multimorbidité, définie comme étant la présence de ≥ 2 affections chroniques selon l'indice de comorbidité d'Elixhauser. RéSULTATS: Dans l'échantillon CEM (n = 1 962 survivants de la tuberculose; n = 1 962 témoins sans tuberculose), nous avons estimé que 21,2 % des survivants de la tuberculose (n = 416), contre 12 % des témoins sans tuberculose (n = 236), étaient atteints de multimorbidité. Dans notre analyse primaire, nous avons obtenu un ratio de prévalence doublement ajusté de 1,74 (IC de 95 % : 1,49-2,05) entre les survivants de la tuberculose et les témoins sans tuberculose appariés pour ce qui est de la multimorbidité. Chez les personnes atteintes de multimorbidité, des différences ont été observées dans la fréquence des maladies chroniques entre les survivants de la tuberculose et les témoins appariés. CONCLUSION: Les survivants de la tuberculose avaient une prévalence de multimorbidité supérieure de 74 % à celle des témoins sans tuberculose appariés selon la méthode CEM. Les structures de multimorbidité propres à la tuberculose ont été observées selon les différences dans la fréquence des maladies chroniques entre les échantillons appariés. Ces constatations indiquent qu'il faudrait mener des interventions sur la multimorbidité propres à la tuberculose dans des milieux à revenu élevé comme le Canada. Nous suggérons d'utiliser la survie à la tuberculose comme cadre d'élaboration d'interventions centrées sur la personne pour lutter contre la multimorbidité chez les survivants de la tuberculose.

Tuberculosis and risk of cancer: A systematic review and meta-analysis.

INTRODUCTION: Cancer is a major cause of death among people who experience tuberculosis (TB), but little is known about its timing and incidence following TB treatment. Our primary objectives were to estimate the pooled risk of all and site-specific malignancies in people with TB compared to the general population or suitable controls. Our secondary objective was to describe the pooled risk of cancer at different time points following TB diagnosis. METHODS: This study was prospectively registered (PROSPERO: CRD42021277819). We systematically searched MEDLINE, Embase, and the Cochrane Database for studies published between 1980 and 2021. We included original observational research articles that estimated cancer risk among people with TB compared to controls. Studies were excluded if they had a study population of fewer than 50 individuals; used cross-sectional, case series, or case report designs; and had a follow-up period of less than 12 months. Random-effects meta-analysis was used to obtain the pooled risk of cancer in the TB population. RESULTS: Of the 5,160 unique studies identified, data from 17 studies were included. When compared to controls, the pooled standardized incidence ratios (SIR) of all cancer (SIR 1.62, 95% CI 1.35-1.93, I2 = 97%) and lung cancer (SIR 3.20, 95% CI 2.21-4.63, I2 = 90%) was increased in the TB population. The pooled risk of all cancers and lung cancer was highest within the first year following TB diagnosis (SIR 4.70, 95% CI 1.80-12.27, I2 = 99%) but remained over five years of follow-up. CONCLUSIONS: People with TB have an increased risk of both pulmonary and non-pulmonary cancers. Further research on cancer following TB diagnosis is needed to develop effective screening and early detection strategies. Clinicians should have a high index of suspicion for cancer in people with TB, particularly in the first year following TB diagnosis.

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.

High-dose rifamycins in the treatment of TB: a systematic review and meta-analysis.

BACKGROUND: There is growing interest in using high-dose rifamycin (HDR) regimens in TB treatment, but the safety and efficacy of HDR regimens remain uncertain. We performed a systematic review and meta-analysis comparing HDR to standard-dose rifamycin (SDR) regimens. METHODS: We searched MEDLINE, Embase, CENTRAL, Cochrane Database of Systematic Reviews and clinicaltrials.gov for prospective studies comparing daily therapy with HDRs to SDRs. Rifamycins included rifampicin, rifapentine and rifabutin. Our primary outcome was the rate of severe adverse events (SAEs), with secondary outcomes of death, all adverse events, SAE by organ and efficacy outcomes of 2-month culture conversion and relapse. This study was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42020142519). RESULTS: We identified 9057 articles and included 13 studies with 6168 participants contributing 7930 person-years (PY) of follow-up (HDR: 3535 participants, 4387 PY; SDR: 2633 participants, 3543 PY). We found no significant difference in the pooled incidence rate ratio (IRR) of SAE between HDR and SDR (IRR 1.00, 95% CI 0.82 to 1.23, I 2=41%). There was no significant difference when analysis was limited to SAE possibly, probably or likely medication-related (IRR 1.07, 95% CI 0.82 to 1.41, I 2=0%); studies with low risk of bias (IRR 0.98, 95% CI 0.79 to 1.20, I 2=44%); or studies using rifampicin (IRR 1.00, 95% CI 0. 0.75-1.32, I 2=38%). No significant differences were noted in pooled outcomes of death, 2-month culture conversion and relapse. CONCLUSIONS: HDRs were not associated with a significant difference in SAEs, 2-month culture conversion or death. Further studies are required to identify specific groups who may benefit from HDR.

Changes in pulmonary function and patient-reported outcomes during COVID-19 recovery: a longitudinal, prospective cohort study.

OBJECTIVES: The aim of this study was to compare respiratory and patient-reported outcome measures (PROMs) between 3 and 6 months after symptom onset and to identify features that predict these changes. METHODS: This was a consecutive prospective cohort of 73 patients who were hospitalised with coronavirus disease 2019 (COVID-19). We evaluated the changes in pulmonary function tests and PROMs between 3 and 6 months and then investigated the associations between outcomes (change in diffusing capacity of the lung for carbon monoxide (D LCO), dyspnoea and quality of life (QoL)) and clinical and radiological features. RESULTS: There was improvement in forced vital capacity, total lung capacity and D LCO between 3 and 6 months by 3.25%, 3.82% and 5.69%, respectively; however, there was no difference in PROMs. Reticulation and total computed tomography (CT) scores were associated with lower D LCO % predicted at 6 months (coefficients; -8.7 and -5.3, respectively). The association between radiological scores and D LCO were modified by time, with the degree of association between ground glass and D LCO having decreased markedly over time. There was no association between other predictors and change in dyspnoea or QoL over time. CONCLUSIONS: There is improvement in pulmonary function measurements between 3 and 6 months after COVID-19 symptom onset; however, PROMs did not improve. A higher reticulation and total CT score are negatively associated with D LCO, but this association is attenuated over time. Lastly, there is a considerable proportion of patients with unexplained dyspnoea at 6 months, motivating further research to identify the underlying mechanisms.