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.

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.

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.

A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations.

The long-term respiratory morbidity of COVID-19 remains unclear. We describe the clinical, radiological and pulmonary function abnormalities that persist in previously hospitalised patients assessed 12 weeks after COVID-19 symptom onset, and identify clinical predictors of respiratory outcomes. At least one pulmonary function variable was abnormal in 58% of patients and 88% had abnormal imaging on chest CT. There was strong association between days on oxygen supplementation during the acute phase of COVID-19 and both DLCO-% (diffusion capacity of the lung for carbon monoxide) predicted and total CT score. These findings highlight the need to develop treatment strategies and the importance of long-term respiratory follow-up after hospitalisation for COVID-19.

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Eligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset. RESULTS: 5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%). CONCLUSION: Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests. STUDY REGISTRATION: PROSPERO CRD42020179452.