Comparing the Hospital Frailty Risk Score and the Clinical Frailty Scale Among Older Adults With Chronic Obstructive Pulmonary Disease Exacerbation.

Importance: Frailty is associated with severe morbidity and mortality among people with chronic obstructive pulmonary disease (COPD). Interventions such as pulmonary rehabilitation can treat and reverse frailty, yet frailty is not routinely measured in pulmonary clinical practice. It is unclear how population-based administrative data tools to screen for frailty compare with standard bedside assessments in this population. Objective: To determine the agreement between the Hospital Frailty Risk Score (HFRS) and the Clinical Frailty Scale (CFS) among hospitalized individuals with COPD and to determine the sensitivity and specificity of the HFRS (vs CFS) to detect frailty. Design, Setting, and Participants: A cross-sectional study was conducted among hospitalized patients with COPD exacerbation. The study was conducted in the respiratory ward of a single tertiary care academic hospital (The Ottawa Hospital, Ottawa, Ontario, Canada). Participants included consenting adult inpatients who were admitted with a diagnosis of acute COPD exacerbation from December 2016 to June 2019 and who used a clinical care pathway for COPD. There were no specific exclusion criteria. Data analysis was performed in March 2022. Exposure: Degree of frailty measured by the CFS. Main Outcomes and Measures: The HFRS was calculated using hospital administrative data. Primary outcomes were the sensitivity and specificity of the HFRS to detect frail and nonfrail individuals according to CFS assessments of frailty, and the secondary outcome was the optimal probability threshold of the HFRS to discriminate frail and nonfrail individuals. Results: Among 99 patients with COPD exacerbation (mean [SD] age, 70.6 [9.5] years; 56 women [57%]), 14 (14%) were not frail, 33 (33%) were vulnerable, 18 (18%) were mildly frail, and 34 (34%) were moderately to severely frail by the CFS. The HFRS (vs CFS) had a sensitivity of 27% and specificity of 93% to detect frail vs nonfrail individuals. The optimal probability threshold for the HFRS was 1.4 points or higher. The corresponding sensitivity to detect frailty was 69%, and the specificity was 57%. Conclusions and Relevance: In this cross-sectional study, using the population-based HFRS to screen for frailty yielded poor detection of frailty among hospitalized patients with COPD compared with the bedside CFS. These findings suggest that use of the HFRS in this population may result in important missed opportunities to identify and provide early intervention for frailty, such as pulmonary rehabilitation.

Effect of implementation of a 12-dose once-weekly treatment (3HP) in addition to standard regimens to prevent TB on completion rates: Interrupted time series design.

OBJECTIVES: We aimed to determine if offering a 12-dose once-weekly treatment (3HP) as an additional treatment option would result in an increase in the overall proportion of patients completing TB preventive treatment (TPT) above the baseline rate. METHODS: We analyzed outcomes in consecutive adults referred to a TB clinic from January 2010 to May 2019. Starting December 2016, 3HP was offered as an alternative to standard clinic regimens which included 9 months of daily isoniazid or 4 months of daily rifampin. The primary outcome was the proportion of patients who completed TPT among all patients who started treatment. Using segmented autoregression analysis, we compared completion at the end of the study with projected completion had the intervention not been introduced. RESULTS: A total of 2803 adults were referred for assessment over the study period. There was an absolute increase in completions among those who started a treatment of 19.0% at the end of the study between the observed intervention completion rate and the projected completion rate from the baseline study period (the completion rate had the 3HP intervention not been introduced) (76% observed vs 57% projected; 95% CI 6.6 to 31.4%; p = 0.004) and an absolute increase among those who were offered treatment (17.3%; 95% CI, 2.3 to 32.3%; p = 0.025). CONCLUSIONS: The introduction of 3HP for TPT as an alternative to the regular regimens offered resulted in a significant increase in the proportion of patients completing treatment. Our study provides evidence to support accelerated use of 3HP in Canada.

Cost-effectiveness analysis of 3 months of weekly rifapentine and isoniazid compared to isoniazid monotherapy in a Canadian arctic setting.

OBJECTIVE: To assess the cost effectiveness of once weekly rifapentine and isoniazid for 12 weeks (3HP) to the current standard care for latent tuberculosis (TB) infection (LTBI) in Iqaluit, Nunavut. DESIGN: A cost-effectiveness analysis using a Markov model reflecting local practices for LTBI treatment. SETTING: A remote Canadian arctic community with a high incidence of TB. PARTICIPANTS: Hypothetical patients with LTBI. INTERVENTIONS: The cost effectiveness of 3HP was compared with the existing standard of care in the study region which consists of 9 months of twice weekly isoniazid (9H) given by directly observed therapy. OUTCOME MEASURES: Effectiveness was measured in quality-adjusted life years (QALYs) with model parameters were derived from historical programmatic data, a local implementation study of 3HP and published literature. Costs from the perspective of the Nunavut healthcare system were measured in 2019 US dollars and were obtained primarily from local, empirically collected data. Secondary health outcomes included estimated TB cases and TB deaths averted using 3HP versus 9H. One way and probabilistic sensitivity analyses were performed. RESULTS: The 3HP regimen was dominant over 9H: costs were lower (US$628 vs US$924/person) and health outcomes slightly improved (20.14 vs 20.13 QALYs/person). In comparison to 9H, 3HP treatment resulted in fewer TB cases (27.89 vs 30.16/1000 persons) and TB deaths (2.29 vs 2.48/1000 persons). 3HP completion, initiation and risk of fatal adverse events were the primary drivers of cost effectiveness. CONCLUSION: In a remote Canadian arctic setting, using 3HP instead of 9H for LTBI treatment may result in cost savings and similar or improved health outcomes.

Molecular Epidemiology of Mycobacterium tuberculosis To Describe the Transmission Dynamics Among Inuit Residing in Iqaluit Nunavut Using Whole-Genome Sequencing.

BACKGROUND: In the last decade, tuberculosis (TB) incidence among Inuit in the Canadian Arctic has been rising. Our aim was to better understand the transmission dynamics of TB in this remote region of Canada using whole-genome sequencing. METHODS: Isolates from patients who had culture-positive pulmonary TB in Iqaluit, Nunavut, between 2009 and 2015 underwent whole-genome sequencing (WGS). The number of transmission events between cases within clusters was calculated using a threshold of a ≤3 single nucleotide polymorphism (SNP) difference between isolates and then combined with detailed epidemiological data using a reproducible novel algorithm. Social network analysis of epidemiological data was used to support the WGS data analysis. RESULTS: During the study period, 140 Mycobacterium tuberculosis isolates from 135 cases were sequenced. Four clusters were identified, all from Euro-American lineage. One cluster represented 62% of all cases that were sequenced over the entire study period. In this cluster, 2 large chains of transmission were associated with 3 superspreading events in a homeless shelter. One of the superspreading events was linked to a nonsanctioned gambling house that resulted in further transmission. Shelter to nonshelter transmission was also confirmed. An algorithm developed for the determination of transmission events demonstrated very good reproducibility (κ score .98, 95% confidence interval, .97-1.0). CONCLUSIONS: Our study suggests that socioeconomic factors, namely residing in a homeless shelter and spending time in a gambling house, combined with the superspreading event effect may have been significant factors explaining the rise in cases in this predominantly Inuit Arctic community.

Genetic and environmental influences on the developmental trajectory of callous-unemotional traits from childhood to adolescence.

BACKGROUND: This study examined the genetic and environmental influences underlying baseline level and developmental course of callous-unemotional (CU) traits across childhood and adolescence. METHODS: The data on 8,958 twin pairs (3,108 MZ twin pairs and 5,850 DZ twin pairs) from the Twins Early Development Study were analysed. CU traits were assessed at ages 7, 9, 12 and 16 by mothers and analysed using a biometric latent growth model. RESULTS: Individual differences in the baseline level of CU traits were highly heritable (76.5%), while the heritability of the developmental course of CU traits was moderate (43.6%). The genetic influences on baseline level and developmental course of CU traits were mostly nonoverlapping. Nonshared environment made a modest contribution to the baseline level of CU traits (21.7%). Nonshared environmental influences on the developmental course of CU traits were moderate (43.2%), with nearly half of them being the same as those influencing the baseline level and just over half being specific. Shared environmental effects did not contribute to systematic change across childhood and adolescence but were rather age-specific. CONCLUSIONS: Our findings demonstrate that rather than only being conceptualized as factors of stability, genes also play a dynamic role in explaining systematic change in CU traits. Genetic effects for the initial risk and subsequent development of CU traits are not the same. In addition to genetic factors, nonshared environmental influences play an important role in explaining why some children will increase or maintain their CU traits over time, whereas other will desist. New genetic and environmental influences with age suggest that repeated, age-tailored interventions may be required throughout development to make a lasting difference in the presentation of CU traits and associated outcomes.

The latent tuberculosis infection cascade of care in Iqaluit, Nunavut, 2012-2016.

BACKGROUND: A remote arctic region of Canada predominantly populated by Inuit with the country's highest incidence of tuberculosis. METHODS: The study was undertaken to describe the latent tuberculosis infection (LTBI) cascade of care and identify factors associated with non-initiation and non-completion of LTBI treatment. Data were extracted retrospectively from medical records for all patients with a tuberculin skin test (TST) implanted in Iqaluit, Nunavut between January 2012 and March 2016. Associations between demographic and clinical factors and both treatment non-initiation among and treatment non-completion were identified using log binomial regression models where convergence could be obtained and Poisson models with robust error variance where convergence was not obtained. RESULTS: Of 2303 patients tested, 439 (19.1%) were diagnosed with LTBI. Treatment was offered to 328 patients, was initiated by 246 (75.0% of those offered) and was completed by 186 (75.6% of initiators). In multivariable analysis, older age (adjust risk ratio [aRR] 1.17 per 5-year increase, 95%CI:1.09-1.26) and undergoing TST due to employment screening (aRR 1.63, 95%CI:1.00-2.65, compared to following tuberculosis exposure) were associated with increased non-initiation of treatment. Older age (aRR 1.13, 95%CI: 1.03-1.17, per 5-year increase) was associated with increased non-completion of treatment. CONCLUSIONS: A similar rate of treatment initiation and higher rate of treatment completion were found compared to previous North American studies. Interventions targeting older individuals and those identified via employment screening may be considered to help to address the largest losses in the cascade of care.

Social determinants of health among residential areas with a high tuberculosis incidence in a remote Inuit community.

BACKGROUND: Tuberculosis (TB) remains a significant health burden among Inuit in Canada. Social determinants of health (SDH) play a key role in TB infection, disease and ongoing transmission in this population. The objective of this research was to estimate the prevalence of social determinants of Inuit health as they relate to latent TB infection (LTBI) among people living in residential areas at high risk for TB in Iqaluit, Nunavut. METHODS: Inperson home surveys were conducted among those who lived in predetermined residential areas at high risk for TB identified in a door-to-door TB prevention campaign in Iqaluit, Nunavut in 2011. Risk ratios for SDH and LTBI were estimated, and multiple imputation was used to address missing data. RESULTS: 261 participants completed the questionnaire. Most participants identified as Inuit (82%). Unadjusted risk ratios demonstrated that age, education, smoking tobacco, crowded housing conditions and Inuit ethnicity were associated with LTBI. After adjusting for other SDH, multivariable analysis showed an association between LTBI with increasing age (relative risk, RR 1.07, 95% CI 1.04 to 1.11), crowded housing (RR 1.48, 95% CI 1.10 to 2.00) and ethnicity (RR 2.76, 95% CI 1.33 to 5.73) after imputing missing data. CONCLUSION: Among high-risk residential areas for TB in a remote Arctic region of Canada, crowded housing and Inuit ethnicity were associated with LTBI after adjusting for other SDH. In addition to strong screening and treatment programmes, alleviating the chronic housing shortage will be a key element in the elimination of TB in the Canadian Inuit Nunangat.

Catheter Tract Metastasis in Mesothelioma Patients with Indwelling Pleural Catheters: A Retrospective Cohort Study.

BACKGROUND: Use of indwelling pleural catheters (IPCs) for the management of symptomatic pleural effusions in patients with mesothelioma has increased in popularity. An important concern with this approach is the potential for the development of catheter tract metastasis (CTM). OBJECTIVES: To determine the incidence of IPC-related CTM in patients with malignant pleural mesothelioma (MPM). METHODS: In this single-center retrospective cohort study, patients with biopsy-confirmed MPM who had an IPC inserted between May 2006 and July 2017 were identified from a prospectively collected database. Thoracic CT scans following IPC insertion were reviewed to assess for evidence of CTM. Patients were followed until death or last documented patient encounter with a minimum of 6-month follow-up. RESULTS: A total of 90 patients were included in the cohort. CTM was identified in 23 of 90 patients (26%). Median time from IPC insertion to CTM was 408 days (interquartile range 196-721 days). Medical thoracoscopy at the time of IPC insertion did not lead to a significantly increased odds of CTM (OR 2.30; 95% CI 0.66-7.94; p = 0.19). Incidence of CTM was not different between mesothelioma subtypes (p = 0.09). Patient-reported dyspnea scores were improved following IPC insertion in 80% of patients. CONCLUSIONS: CTM was identified in over a quarter of MPM patients when follow-up imaging was reviewed. Treating physicians should be cognizant of the possibility of CTM at the site of prior IPC.

A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection.

PURPOSE: Tuberculosis (TB) remains a common cause of death globally. A regimen of 12 doses of isoniazid (INH) and rifapentine given once weekly (INH/RPT-3) has recently been recommended by the World Health Organization for the treatment of latent TB infection (LTBI). We aimed to determine whether the INH/RPT-3 regimen had similar or lesser rates of adverse events compared to other LTBI regimens, namely INH for 9 months, INH for 6 months, rifampin for 3 to 4 months, and rifampin plus INH for 3 to 4 months. METHODS: We searched MEDLINE, Embase, CENTRAL, PubMed, ICTRP, clinicaltrials.gov, and Canadian Agency for Drugs and Technologies in Health's Gray Matters Light for randomized, postmarketing, and comparative nonrandomized studies of patients with confirmed LTBI that reported the frequency of at least 1 adverse event of relevance for a regimen of interest. The search included studies published until March 2017. The frequencies of adverse events were extracted and are presented descriptively. RESULTS: Data from 23 randomized and 55 nonrandomized studies were included. Although inconsistent event reporting and high heterogeneity limited comparisons, the adverse event profile of INH/RPT-3 appeared generally favorable. Flu-like reactions were reported with an increased frequency and hepatotoxicity with a lower frequency than standard treatment. CONCLUSIONS: While INH/RPT-3 had an overall low frequency of adverse events compared to INH monotherapy, reporting of adverse events for many regimens was limited meaning results should be interpreted cautiously. Future studies of LTBI treatment would benefit from more complete collection and reporting of adverse events and more consistent definitions of hepatotoxicity.

Efficacy and completion rates of rifapentine and isoniazid (3HP) compared to other treatment regimens for latent tuberculosis infection: a systematic review with network meta-analyses.

BACKGROUND: We conducted a systematic review and network meta-analysis (NMA) to examine the efficacy and completion rates of treatments for latent tuberculosis infection (LTBI). While a previous review found newer, short-duration regimens to be effective, several included studies did not confirm LTBI, and analyses did not account for variable follow-up or assess completion. METHODS: We searched MEDLINE, Embase, CENTRAL, PubMed, and additional sources to identify RCTs in patients with confirmed LTBI that involved a regimen of interest and reported on efficacy or completion. Regimens of interest included isoniazid (INH) with rifapentine once weekly for 12 weeks (INH/RPT-3), 6 and 9 months of daily INH (INH-6; INH-9), 3-4 months daily INH plus rifampicin (INH/RFMP 3-4), and 4 months daily rifampicin alone (RFMP-4). NMAs were performed to compare regimens for both endpoints. RESULTS: Sixteen RCTs (n = 44,149) and 14 RCTs (n = 44,128) were included in analyses of efficacy and completion. Studies were published between 1968 and 2015, and there was diversity in patient age and comorbidities. All regimens of interest except INH-9 showed significant benefits in preventing active TB compared to placebo. Comparisons between active regimens did not reveal significant differences. While definitions of regimen completion varied across studies, regimens of 3-4 months were associated with a greater likelihood of adequate completion. CONCLUSIONS: Most of the active regimens showed an ability to reduce the risk of active TB relative to no treatment, however important differences between active regimens were not found. Shorter rifamycin-based regimens may offer comparable benefits to longer INH regimens. Regimens of 3-4 months duration are more likely to be completed than longer regimens.

Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy.

Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P = 0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P = 0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.

Canadian variation by province in rheumatoid arthritis initiating anti-tumor necrosis factor therapy: results from the optimization of adalimumab trial.

OBJECTIVE: We compared variations among Canadian provinces in rheumatoid arthritis (RA) initiating anti-tumor necrosis factor (TNF) therapy. METHODS: Data were obtained from the Optimization of Humira trial (OH) and from the Ontario Biologics Research Initiative (OBRI). Baseline characteristics were compared between regions: Ontario (ON), Quebec (QC), and other provinces (OTH). We compared Ontario OH to OBRI patients who were initiating anti-TNF therapy. RESULTS: In 300 OH patients, mean age was 54.8 years (13.3). There were 151 (50.3%) ON patients, 57 from QC (19%), and 92 from OTH (30.7%). Regional differences were seen in the number of disease-modifying antirheumatic drugs (DMARD) ever taken (ON: 3.8 ± 1.4, QC: 3.1 ± 1.1, OTH: 3.3 ± 1.4; p < 0.001); swollen joint count (SJC; ON: 10.9 ± 5.9, QC: 9.0 ± 4.4, OTH: 11.3 ± 5.6; p = 0.033); tender joint count (TJC; ON: 12.2 ± 7.5, QC: 10.3 ± 5.7, OTH: 14.4 ± 7.6; p = 0.003); 28-joint Disease Activity Score (DAS28; ON: 5.8 ± 1.2, QC: 5.6 ± 1.0, OTH: 6.0 ± 1.1; p = 0.076); and Health Assessment Questionnaire (ON: 1.4 ± 0.7, QC: 1.7 ± 0.7, OTH: 1.5 ± 0.7; p = 0.060). DMARD-ever use differed: methotrexate (ON: 94.7%, QC: 93%, OTH: 84.8%; p = 0.025); leflunomide (ON: 74.8%, QC: 21.1%, OTH: 51.1%; p < 0.001); sulfasalazine (ON: 51%, QC: 38.6%, OTH: 25%; p < 0.001); myochrysine (ON: 9.3%, QC: 0%, OTH: 15.2%; p = 0.008); and hydroxychloroquine (ON: 67.5%, QC: 86%, OTH: 66.3%; p = 0.018). In comparison to ON OH patients, 95 OBRI patients initiating first anti-TNF had lower SJC (p = 0.017), TJC (p = 0.008), and DAS28 (p = 0.05). CONCLUSION: In Quebec, where access to anti-TNF is less restrictive, patients had lower SJC and TJC. ON used more DMARD, especially leflunomide, as mandated by the provincial government. Both provincial funding criteria and prescribing habits may contribute to differences. Canadian rheumatologists may vary in treatment decisions, but patients generally have similar DAS28 when initiating anti-TNF therapy.