Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial.

Background: In a cluster randomized trial (clinicaltrials.gov: NCT02810678) a flexible but comprehensive health system intervention significantly increased the number of household contacts (HHC) identified and started on tuberculosis preventive treatment (TPT). A follow-up study was conducted one year later to test the hypotheses that these effects were sustained, and were reproducible with a simplified intervention. Methods: We conducted a follow-up study from May 1, 2018 until April 30, 2019, as part of a multinational cluster randomized trial. Eight sites in 4 countries that had received the intervention in the original trial received no further intervention; eight other sites in the same countries that had not received the intervention (control sites in the original trial) now received a simplified version of the intervention. This consisted of repeated local evaluation of the Cascade of care for TB infection, and stakeholder decision making. The number of HHC identified and starting TPT were repeatedly measured at all 16 sites and expressed as rates per 100 newly diagnosed index TB patients. The sustained effect of the original intervention was estimated by comparing these rates after the intervention in the original trial with the last 6 months of the follow-up study. The reproducibility was estimated by comparing the pre-post intervention changes in rates at sites receiving the original intervention with the pre-post changes in rates at sites receiving the later, simplified intervention. Findings: With regard to the sustained impact of the original intervention, compared to the original post-intervention period, the number of HHC identified and treated per 100 newly diagnosed TB patients was 10 more (95% confidence interval: 84 fewer to 105 more), and 1 fewer (95% CI: 22 fewer to 20 more) respectively up to 14 months after the end of the original intervention. With regard to the reproducibility of the simplified intervention, at sites that had initially served as control sites, the number of HHC identified and treated per 100 TB patients increased by 33 (95% CI: -32, 97), and 16 (-69, 100) from 3 months before, to up to 6 months after receiving a streamlined intervention, although differences were larger, and significant if the post-intervention results were compared to all pre-intervention periods. Interpretation: Up to one year after it ended, a health system intervention resulted in sustained increases in the number of HHC identified and starting TPT. A simplified version of the intervention was associated with non-significant increases in the identification and treatment of HHC. Inferences are limited by potential bias due to other temporal effects, and the small number of study sites. Funding: Funded by the Canadian Institutes of Health Research (Grant number 143350).

Exploring obstructive sleep apnea and sleep architecture in Parkinson's disease motor subtypes.

INTRODUCTION: Parkinson's disease (PD) can be divided into motor subtypes: postural instability/gait difficulty (PIGD), tremor dominant, and indeterminate. This study aimed to assess differences in sleep structure and obstructive sleep apnea (OSA) between the PIGD and non-PIGD subtypes. METHODS: PD participants with or without OSA (defined as apnea-hypopnea index (AHI) ≥ 15 events/hour on overnight polysomnography) were included. Patients were separated into two groups: PIGD and non-PIGD. Linear regression was used to explore differences in sleep, AHI, and other respiratory parameters between groups (adjusted for variables determined a priori). Logistic regression adjusted for the same variables was used to determine if the proportion of patients with OSA differed across groups. Subset analyses were performed: subset 1 excluding patients on psychoactive medication; subset 2 excluding patients taking levodopa or dopaminergic agonists (DAs) at nighttime and subset 3 excluding patients on either of the abovementioned drugs. RESULTS: 146 participants were studied. The non-PIGD group had less N3 sleep compared to the PIGD group (12.4% vs 16.9% p = 0.06), reaching significance in subsets 1 and 3. The AHI was significantly lower in the PIGD group (p = 0.047), including when medication effects were removed (p < 0.05). OSA was more frequent in the non-PIGD group, but only significantly in subset 3 (adjusted OR 0.3, p = 0.04). CONCLUSION: OSA may be more severe in non-PIGD subtypes, and more frequent, in a subset free of psychoactive medication, and of levodopa and DAs, possibly owing to motor complications and dyskinesia. Future studies are required to confirm this.

Factors associated with physical function among people with systemic sclerosis: a SPIN cohort cross-sectional study.

OBJECTIVES: To compare physical function in systemic sclerosis (SSc, scleroderma) to general population normative data and identify associated factors. METHODS: Scleroderma Patient-centered Intervention Network Cohort participants completed the Physical Function domain of the Patient-Reported Outcomes Measurement Information System Version 2 upon enrolment. Multivariable linear regression was used to assess associations of sociodemographic, lifestyle, and disease-related variables. RESULTS: Among 2,385 participants, mean physical function T-score (43.7, SD = 8.9) was ∼2/3 of a standard deviation (SD) below the US general population (mean = 50, SD = 10). Factors associated in multivariable analysis included older age (-0.74 points per SD years, 95% CI -0.78 to -1.08), female sex (-1.35, -2.37 to -0.34), fewer years of education (-0.41 points per SD in years, -0.75 to -0.07), being single, divorced, or widowed (-0.76, -1.48 to -0.03), smoking (-3.14, -4.42 to -1.85), alcohol consumption (0.79 points per SD drinks per week, 0.45-1.14), BMI (-1.41 points per SD, -1.75 to -1.07), diffuse subtype (-1.43, -2.23 to -0.62), gastrointestinal involvement (-2.58, -3.53 to -1.62), digital ulcers (-1.96, -2.94 to -0.98), moderate (-1.94, -2.94 to -0.93) and severe (-1.76, -3.24 to -0.28) small joint contractures, moderate (-2.10, -3.44 to -0.76) and severe (-2.54, -4.64 to -0.44) large joint contractures, interstitial lung disease (-1.52, -2.27 to -0.77), pulmonary arterial hypertension (-3.72, -4.91 to -2.52), rheumatoid arthritis (-2.10, -3.64 to -0.56) and idiopathic inflammatory myositis (-2.10, -3.63 to -0.56). CONCLUSION: Physical function is impaired for many individuals with SSc and associated with multiple disease factors.

Ongoing Gaps in the Hepatitis C Care Cascade during the Direct-Acting Antiviral Era in a Large Retrospective Cohort in Canada: A Population-Based Study.

To achieve hepatitis C virus (HCV) elimination, high uptake along the care cascade steps for all will be necessary. We mapped engagement with the care cascade overall and among priority groups in the post-direct-acting antivirals (DAAs) period and assessed if this changed relative to pre-DAAs. We created a population-based cohort of all reported HCV diagnoses in Quebec (1990-2018) and constructed the care cascade [antibody diagnosed, RNA tested, RNA positive, genotyped, treated, sustained virologic response (SVR)] in 2013 and 2018. Characteristics associated with RNA testing and treatment initiation were investigated using marginal logistic models via generalized estimating equations. Of the 31,439 individuals HCV-diagnosed in Quebec since 1990 and alive as of 2018, there was significant progress in engagement with the care cascade post- vs. pre-DAAs; 86% vs. 77% were RNA-tested, and 64% vs. 40% initiated treatment. As of 2018, a higher risk of not being RNA-tested or treated was observed among individuals born <1945 vs. >1965 [hazard ratio (HR); 95% CI; 1.35 (1.16-1.57)], those with material and social deprivation [1.21 (1.06-1.38)], and those with alcohol use disorder [1.21 (1.08-1.360]. Overall, non-immigrants had lower rates of RNA testing [0.76 (0.67-0.85)] and treatment initiation [0.63 (0.57-0.70)] than immigrants. As of 2018, PWID had a lower risk of not being RNA tested [0.67 (0.61-0.85)] but a similar risk of not being treated, compared to non-PWID. Engagement in the HCV care cascade have improved in the post-DAA era, but inequities remain. Vulnerable subgroups, including certain older immigrants, were less likely to have received RNA testing or treatment as of 2018 and would benefit from focused interventions to strengthen these steps.

High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial.

BACKGROUND: Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT. METHODS: This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active). RESULTS: Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completion was lower in the 20 mg/kg group (-7·8% [95% CI -13·6 to -2·0]) and the 30 mg/kg group (-15·4% [-21·4 to -9·4]) than in the standard-dose group. INTERPRETATION: In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained. FUNDING: Canadian Institutes of Health Research.

The association of resilience and positive mental health in systemic sclerosis: A Scleroderma Patient-centered Intervention Network (SPIN) cohort cross-sectional study.

OBJECTIVE: A previous study using Scleroderma Patient-centered Intervention Network (SPIN) Cohort data identified five classes of people with systemic sclerosis (also known as scleroderma) based on patient-reported somatic (fatigue, pain, sleep) and mental health (anxiety, depression) symptoms and compared indicators of disease severity between classes. Across four classes ("low", "normal", "high", "very high"), there were progressively worse somatic and mental health outcomes and greater disease severity. The fifth ("high/low") class, however, was characterized by high disease severity, fatigue, pain, and sleep but low mental health symptoms. We evaluated resilience across classes and compared resilience between classes. METHODS: Cross-sectional study. SPIN Cohort participants completed the 10-item Connor-Davidson-Resilience Scale (CD-RISC) and PROMIS v2.0 domains between August 2022 and January 2023. We used latent profile modeling to identify five classes as in the previous study and multiple linear regression to compare resilience levels across classes, controlling for sociodemographic and disease variables. RESULTS: Mean CD-RISC score (N = 1054 participants) was 27.7 (standard deviation = 7.3). Resilience decreased progressively across "low" to "normal" to "high" to "very high" classes (mean 4.7 points per step). Based on multiple regression, the "high/low" class exhibited higher resilience scores than the "high" class (6.0 points, 95% confidence interval [CI] 4.9 to 7.1 points; standardized mean difference = 0.83, 95% CI 0.67 to 0.98). CONCLUSIONS: People with worse disease severity and patient-reported outcomes reported substantially lower resilience, except a class of people with high disease severity, fatigue, pain, and sleep disturbance but positive mental health and high resilience.

Factors associated with satisfaction with social roles and activities among people with systemic sclerosis: a Scleroderma Patient-centered Intervention Network (SPIN) cohort cross-sectional study.

OBJECTIVE: The objectives were to (1) compare satisfaction with social roles and activities in a large multinational systemic sclerosis (SSc) cohort to general population normative data and (2) identify sociodemographic, lifestyle and SSc disease factors associated with satisfaction with social roles and activities. METHODS: Participants in the Scleroderma Patient-centered Intervention Network Cohort completed the Patient Reported Outcomes Information System Version 2 satisfaction with social roles and activities domain questionnaire. Multivariable regression was used to assess associations with sociodemographic, lifestyle and disease factors. RESULTS: Among 2385 participants, mean satisfaction with social roles and activities T-score (48.1, SD=9.9) was slightly lower than the US general population (mean=50, SD=10). Factors independently associated with satisfaction were years of education (0.54 per SD, 95% CI 0.14 to 0.93); non-White race or ethnicity (-1.13, 95% CI -2.18 to -0.08); living in Canada (-1.33, 95% CI -2.40 to -0.26 (reference USA)) or the UK (-2.49, 95% CI -3.92 to -1.06); body mass index (-1.08 per SD, 95% CI -1.47 to -0.69); gastrointestinal involvement (-3.16, 95% CI -4.27 to -2.05); digital ulcers (-1.90, 95% CI -3.05 to -0.76); moderate (-1.62, 95% CI -2.78 to -0.45) or severe (-2.26, 95% CI -3.99 to -0.52) small joint contractures; interstitial lung disease (-1.11, 95% CI -1.97 to -0.25); pulmonary arterial hypertension (-2.69, 95% CI -4.08 to -1.30); rheumatoid arthritis (-2.51, 95% CI -4.28 to -0.73); and Sjogren's syndrome (-2.42, 95% CI -3.96 to -0.88). CONCLUSION: Mean satisfaction with social roles and activities is slightly lower in SSc than the general population and associated with multiple sociodemographic and disease factors.

An Automated Insulin Delivery System with Automatic Meal Bolus Based on a Hand-Gesturing Algorithm.

Background: Carbohydrate counting (CC) and meal announcements, before eating, introduce a significant burden for individuals managing type 1 diabetes (T1D). An automated insulin delivery system with automatic bolusing that eliminates the need for CC and premeal bolusing (i.e., a hands-free closed-loop [HFCL] system) was assessed in a feasibility trial of adults with T1D. Methods: The system included the MiniMed™ 780G pump and a smartphone-paired smartwatch with the Klue application (Klue, Inc.) that detects eating and drinking gestures. A smartphone algorithm converted gestures into carb amounts that were transmitted to the pump for automatic bolusing. For 5 days, participants (N = 17, 18-75 years of age) used the system at home with meal announcements based on traditional CC, with the Klue application disabled (Home-stay phase). Thereafter, participants moved to a supervised hotel setting, where the Klue application was enabled for 5 days and meals were not announced (Hotel-stay phase). Participants consumed the same eight test meals (six solid and two liquid) of varying caloric and carb size at the same time and day of the week for both phases, and glycemic metrics were compared. Otherwise, there were no other meal restrictions. Results: The overall time in range (70-180 mg/dL) was 83.4% ± 7.0% and 80.6% ± 6.7% for the Home-stay and Hotel-stay, respectively (P = 0.08). The average time at <70 mg/dL was 3.1% and 3.0% (P = 0.9144), respectively, and the average time at >180 mg/dL was 13.5% and 16.3% (P = 0.1046), respectively. Postprandial glycemia following low-carb test meals was similar between the two phases. The system's ability to accommodate high-carb meals was somewhat limited. There were no episodes of severe hypoglycemia or diabetic ketoacidosis. Conclusion: Preliminary findings show that a HFCL system was safe and maintained overall glycemic control, similar to that observed with traditional CC and manual meal bolusing. By eliminating these daily T1D burdens, a HFCL system may improve quality of life for individuals with T1D. ClinicalTrials.gov number: NCT04964128.

An empirical comparison of statistical methods for multiple cut-off diagnostic test accuracy meta-analysis of the Edinburgh postnatal depression scale (EPDS) depression screening tool using published results vs individual participant data.

BACKGROUND: Selective reporting of results from only well-performing cut-offs leads to biased estimates of accuracy in primary studies of questionnaire-based screening tools and in meta-analyses that synthesize results. Individual participant data meta-analysis (IPDMA) of sensitivity and specificity at each cut-off via bivariate random-effects models (BREMs) can overcome this problem. However, IPDMA is laborious and depends on the ability to successfully obtain primary datasets, and BREMs ignore the correlation between cut-offs within primary studies. METHODS: We compared the performance of three recent multiple cut-off models developed by Steinhauser et al., Jones et al., and Hoyer and Kuss, that account for missing cut-offs when meta-analyzing diagnostic accuracy studies with multiple cut-offs, to BREMs fitted at each cut-off. We used data from 22 studies of the accuracy of the Edinburgh Postnatal Depression Scale (EPDS; 4475 participants, 758 major depression cases). We fitted each of the three multiple cut-off models and BREMs to a dataset with results from only published cut-offs from each study (published data) and an IPD dataset with results for all cut-offs (full IPD data). We estimated pooled sensitivity and specificity with 95% confidence intervals (CIs) for each cut-off and the area under the curve. RESULTS: Compared to the BREMs fitted to the full IPD data, the Steinhauser et al., Jones et al., and Hoyer and Kuss models fitted to the published data produced similar receiver operating characteristic curves; though, the Hoyer and Kuss model had lower area under the curve, mainly due to estimating slightly lower sensitivity at lower cut-offs. When fitting the three multiple cut-off models to the full IPD data, a similar pattern of results was observed. Importantly, all models had similar 95% CIs for sensitivity and specificity, and the CI width increased with cut-off levels for sensitivity and decreased with an increasing cut-off for specificity, even the BREMs which treat each cut-off separately. CONCLUSIONS: Multiple cut-off models appear to be the favorable methods when only published data are available. While collecting IPD is expensive and time consuming, IPD can facilitate subgroup analyses that cannot be conducted with published data only.

Nunavimmi puvakkut kaggutimik aanniaqarniq: Qanuilirqitaa? Lung cancer in Nunavik: How are we doing? A retrospective matched cohort study.

BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.

A Peek Under the Hood: Explaining the MiniMed™ 780G Algorithm with Meal Detection Technology.

The MiniMed™ 780G system (780G) received Conformité Européenne mark in June 2020 and was, recently, approved by the U.S. Food and Drug Administration (April 2023). Clinical trials and real-world analyses have demonstrated MiniMed™ 780G system safety and effectiveness and that glycemic outcomes (i.e., time in range) improve with recommended settings use. In this publication, we will explain the iterative development of the 780G algorithm and how this technology has simplified diabetes management.

Impact of the COVID-19 pandemic on quality of tuberculosis care in private facilities in Bandung, Indonesia: a repeated cross-sectional standardized patients study.

BACKGROUND: Indonesia has the second highest incidence of tuberculosis in the world. While 74% of people with tuberculosis in Indonesia first accessed the private health sector when seeking care for their symptoms, only 18% of tuberculosis notifications originate in the private sector. Little is known about the impact of the COVID-19 pandemic on the private sector. Using unannounced standardized patient visits to private providers, we aimed to measure quality of tuberculosis care during the COVID-19 pandemic. METHODS: A cross-sectional study was conducted using standardized patients in Bandung City, West Java, Indonesia. Ten standardized patients completed 292 visits with private providers between 9 July 2021 and 21 January 2022, wherein standardized patients presented a presumptive tuberculosis case. Results were compared to standardized patients surveys conducted in the same geographical area before the onset of COVID-19. RESULTS: Overall, 35% (95% confidence interval (CI): 29.2-40.4%) of visits were managed correctly according to national tuberculosis guidelines. There were no significant differences in the clinical management of presumptive tuberculosis patients before and during the COVID-19 pandemic, apart from an increase in temperature checks (adjusted odds ratio (aOR): 8.05, 95% CI: 2.96-21.9, p < 0.001) and a decrease in throat examinations (aOR 0.16, 95% CI: 0.06-0.41, p = 0.002) conducted during the pandemic. CONCLUSIONS: Results indicate that providers successfully identify tuberculosis in their patients yet do not manage them according to national guidelines. There were no major changes found in quality of tuberculosis care due to the COVID-19 pandemic. As tuberculosis notifications have declined in Indonesia due to the COVID-19 pandemic, there remains an urgent need to increase private provider engagement in Indonesia and improve quality of care.

Moderators of Loneliness Trajectories in People with Systemic Sclerosis During the COVID-19 Pandemic: A SPIN COVID-19 Cohort Longitudinal Study.

BACKGROUND: Many individuals with systemic sclerosis (SSc) are at heightened risk for COVID-19 related morbidity and isolation due to interstitial lung disease, frailty, and immunosuppressant use. Minimal research has explored loneliness predictors in individuals with chronic illnesses during COVID-19. This study evaluated moderators of loneliness trajectories in individuals with SSc during COVID-19. METHODS: Longitudinal data were analyzed across 30 timepoints from April 2020 to May 2022 from 775 adults in the Scleroderma Patient-centered Intervention Network (SPIN) COVID-19 Cohort. Hierarchical linear modeling evaluated cross-level moderators of loneliness trajectories, including marital status, baseline number of household members, number of virtual or telephone one-on-one or virtual group conversations, number of hours spent enjoying in-person household conversations or activities, and satisfaction with quality of in-person household conversations (all in the past week). Level-1 moderation analyses assessed effects of conversation, activity, and satisfaction means and slopes over time. RESULTS: Baseline values were not statistically significant moderators of loneliness trajectories. Higher mean (averaged over time) virtual or telephone one-on-one and in-person household conversations, in-person household activity, and in-person household conversation satisfaction were associated with lower loneliness trajectories (ps < .05). The relationship between in-person household conversation satisfaction and loneliness trajectory was statistically significantly but minimally attenuated over time (p < .001). CONCLUSIONS: For people with SSc, higher mean conversation, activity, and satisfaction variables were associated with lower levels of loneliness during the pandemic, but changes in these social variables were generally not predictive of changes in loneliness.

PAP Treatment of Obstructive Sleep Apnea-Hypopnea in Hypertensive Disorders of Pregnancy: A Pilot Randomized Proof-of-the-Concept Study.

RATIONALE: Maternal obstructive sleep apnea-hypopnea (OSAH) is associated with hypertensive disorders of pregnancy (HDP). OSAH treatment with positive airway pressure (PAP) in the general population lowers blood pressure (BP). However, there is limited data on the effects of PAP therapy in maternal OSAH. OBJECTIVE: Our primary objective was to assess the feasibility of recruitment to a pilot randomized trial and adherence to PAP therapy for OSAH in women with HDP. Secondary objectives included assessment of PAP effects on 24-h BP, arterial stiffness, and maternal and fetal outcomes. METHODS: Women with a singleton pregnancy ≥ 12 weeks' gestation and hypertension underwent home level II PSG; those with mild-moderate OSAH (AHI ≥ 5 events/h; severe OSAH with AHI >30 and ODI > 30 excluded) were randomized to either PAP or nasal dilator strip (NDS; control) therapy. Following PAP education, adherence was monitored online with episodic phone or in-person support by research personnel. 24-h BP and arterial stiffness were assessed at baseline and pre-delivery. Maternal and fetal outcomes were also recorded. RESULTS: Of 105 potentially eligible participants, 67 agreed to undergo screening for OSAH over 38 months; 48 women meeting OSAH inclusion criteria were randomized to PAP (n=27) or NDS (n=21). Of these, 14 PAP (52%) and 13 NDS (62%) participants completed all predelivery measurements, with lack of completion due to urgent delivery (PAP 19%, NDS 14%), PAP intolerance at initiation (19%) or other factors. Mean PAP use was 3.1±2.5 h/night, with use ≥ 4 h/night on 38.4 ± 33.7% of nights during 9.6 ± 4.0 weeks of treatment. BP was controlled within target range in most participants. There were no differences in mean change in 24-h BP or arterial stiffness measurements or in adverse maternal & fetal outcomes, between PAP and NDS groups in either intention-to-treat or per-protocol analyses. CONCLUSION: CPAP adherence was sub-optimal in this HDP cohort despite education and trouble-shooting. Further work is required to identify optimal OSAH treatment strategies during pregnancy. CLINICAL TRIAL REGISTRATION: NCT03309826.

Impact of Language Barriers on Outcomes and Experience of COVID-19 Patients Hospitalized in Quebec, Canada, During the First Wave of the Pandemic.

Language barriers (LB) contribute to coronavirus disease 2019 (COVID-19) health inequities. People with LB were more likely to be SARS-CoV-2 positive despite lower testing and had higher rates of hospitalization. Data on hospital outcomes among immigrants with LB, however, are limited. We aimed to investigate the clinical outcomes of hospitalized COVID-19 cases by LB, immigration status, ethnicity, and access to COVID-19 health information and services prior to admission. Adults with laboratory-confirmed community-acquired COVID-19 hospitalized from March 1 to June 30, 2020, at four tertiary-care hospitals in Montréal, Quebec, Canada were included. Demographics, comorbidities, immigration status, country of birth, ethnicity, presence of LB, and hospital outcomes (ICU admission and death) were obtained through a chart review. Additional socio-economic and access to care questions were obtained through a phone survey. A Fine-Gray competing risk subdistribution hazards model was used to estimate the risk of ICU admission and in-hospital death by immigrant status, region of birth and LB Among 1093 patients, 622 (56.9%) were immigrants and 101 (16.2%) of them had a LB. One third (36%) of immigrants with LB did not have access to an interpreter during hospitalization. Admission to ICU and in-hospital mortality were not significantly different between groups. Prior to admission, one third (14/41) of immigrants with LB had difficulties accessing COVID-19 information in their mother tongue and one third (9/27) of non-white immigrants with a LB had difficulties accessing COVID-19 services. Immigrants with LB were inequitably affected by the first wave of the pandemic in Quebec, Canada. In our study, a large proportion had difficulties accessing information and services related to COVID-19 prior to admission, which may have increased SARS-CoV-2 exposure and hospitalizations. After hospitalization, a large proportion did not have access to interpreters. Providing medical information and care in the language of preference of increasing diverse populations in Canada is important for promoting health equity.

Long term effects of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea syndrome in multiple sclerosis patients.

BACKGROUND: Obstructive sleep apnea-hypopnea (OSAH) is common in MS patients and is associated with fatigue. We recently published a randomized, controlled trial (RCT) of active vs sham continuous positive airway pressure (CPAP) treatment in MS patients with fatigue, poor sleep quality, and (OSAH) (Mult Scl J 2022;28:82-92). Our aim was to evaluate the long-term effects of CPAP treatment on fatigue (Fatigue Severity Scale, FSS, primary outcome) and other clinical outcomes in MS patients with OSAH. METHODS: Following the RCT, participants were offered treatment with CPAP and participation in an open label study. Patients were re-evaluated with RCT outcome measures at least 6 months after completion of the RCT. RESULTS: Twenty-eight of 34 (82 %) RCT-completers participated in this study a mean of 2.7 years after the RCT. Sixteen (57 %) patients were treated with CPAP (mean use 5.4 ± 1.0 h/night during the 6 months prior to follow-up visit), while the other 12 patients declined CPAP use and received no other OSAH treatments. Baseline clinical characteristics, including MS related disability and sleep outcomes, were not significantly different between CPAP-treated vs non-CPAP treated patients. Patients using CPAP at follow-up (n = 16) demonstrated significant improvements from RCT baseline in FSS (p = 0.005), Fatigue Scale for Motor and Cognitive Functions (p = 0.008, p = 0.012), Pittsburgh Sleep Quality Index (p = 0.016), Center of Epidemiological Studies-Depression Scale (p = 0.05), and Multiple Sclerosis Quality of Life-54 (MSQOL-54) physical and mental component scores (p = 0.012, p = 0.023), but no improvements in Epworth Sleepiness Scale, Pain Visual Analog Scale, or Expanded Disability Status Scale. Patients not using CPAP (n = 12) had no significant improvements in outcome measures. Using a linear mixed model, FSS (p = 0.03), morning fatigue (p = 0.048), and MSQOL-54 physical component score (p = 0.02) improved significantly in CPAP treated patients compared with non-CPAP treated patients from RCT baseline. CONCLUSION: In this post-RCT open label study, long-term CPAP use was associated with improved fatigue (FSS, our primary outcome) and physical quality of life in MS patients with OSAH.

Two-stage targeted maximum likelihood estimation for mixed aggregate and individual participant data analysis with an application to multidrug resistant tuberculosis.

In this study, we develop a new method for the meta-analysis of mixed aggregate data (AD) and individual participant data (IPD). The method is an adaptation of inverse probability weighted targeted maximum likelihood estimation (IPW-TMLE), which was initially proposed for two-stage sampled data. Our methods are motivated by a systematic review investigating treatment effectiveness for multidrug resistant tuberculosis (MDR-TB) where the available data include IPD from some studies but only AD from others. One complication in this application is that participants with MDR-TB are typically treated with multiple antimicrobial agents where many such medications were not observed in all studies considered in the meta-analysis. We focus here on the estimation of the expected potential outcome while intervening on a specific medication but not intervening on any others. Our method involves the implementation of a TMLE that transports the estimation from studies where the treatment is observed to the full target population. A second weighting component adjusts for the studies with missing (inaccessible) IPD. We demonstrate the properties of the proposed method and contrast it with alternative approaches in a simulation study. We finally apply this method to estimate treatment effectiveness in the MDR-TB case study.

Accuracy of Cytologic vs Histologic Specimens for Assessment of Programmed Cell Death Ligand-1 Expression in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression on tumor cells, evaluated by immunohistochemistry, guides the use of immunotherapy in advanced non-small cell lung cancer (NSCLC). RESEARCH QUESTION: What is the sensitivity and specificity of PD-L1 testing performed in cytologic vs paired histologic specimens in patients with NSCLC? STUDY DESIGN AND METHODS: The MEDLINE, Embase, Web of Science, and Cochrane Library databases were searched through June 1, 2021. The primary outcome was pooled sensitivity and specificity of PD-L1 testing performed on cytologic specimens compared with the reference standard of histologic specimens, analyzed at the PD-L1 expression cutoffs (tumor proportion score) ≥ 1% and ≥ 50%. Pooled sensitivity and specificity, and associated 95% CIs, were estimated using bivariate generalized linear mixed models. RESULTS: Twenty-six articles were included, encompassing a total of 1,064 pairs of histology specimens and cytology cell blocks, and 267 pairs of histology specimens and direct smears. Among these, 946 paired specimens were acquired without interval treatment between the collection of histology and cytology samples. The pooled sensitivity and specificity of cytology specimens compared with paired histology specimens at the PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.77-0.89) and 0.88 (95% CI, 0.82-0.93), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.78 (95% CI, 0.69-0.86) and 0.94 (95% CI, 0.91-0.96), respectively. When only paired specimens acquired without interval treatment were considered, the pooled sensitivity and specificity of cytology specimens at PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.76-0.90) and 0.89 (95% CI, 0.82-0.94), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.80 (95% CI, 0.71-0.89) and 0.94 (95% CI, 0.91-0.96), respectively. INTERPRETATION: Cytologic specimens provide an accurate assessment of PD-L1 expression in most patients with NSCLC, at both ≥ 1% and ≥ 50% cutoffs, when compared with histologic specimens. TRIAL REGISTRATION: PROSPERO; No.: CRD42020153279; URL: https://www.crd.york.ac.uk/prospero/.

metamedian: An R package for meta-analyzing studies reporting medians.

When performing an aggregate data meta-analysis of a continuous outcome, researchers often come across primary studies that report the sample median of the outcome. However, standard meta-analytic methods typically cannot be directly applied in this setting. In recent years, there has been substantial development in statistical methods to incorporate primary studies reporting sample medians in meta-analysis, yet there are currently no comprehensive software tools implementing these methods. In this paper, we present the metamedian R package, a freely available and open-source software tool for meta-analyzing primary studies that report sample medians. We summarize the main features of the software and illustrate its application through real data examples involving risk factors for a severe course of COVID-19.