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Background: Continuous glucose monitors (CGM) could potentially improve management of hyperglycemia compared to standard point of care glucose monitoring for critically ill patients. However, there is limited evidence to support routine use of CGM in the intensive care unit.

Research question: In critically ill patients with hyperglycemia, do CGM improve time within target glucose range compared to standard of care?

Study design and methods: This was an investigator-initiated, single-center, parallel-group, open-label, randomized controlled trial. Adult patients admitted to a medical or surgical intensive care unit, who had diabetes mellitus or hyperglycemia, and were treated with insulin were eligible for enrollment. Participants were randomly assigned to have glucose monitoring performed with CGM (intervention group) or standard of care (control group). Groups were compared for glycemic control and other relevant outcomes. The primary outcome for the study was percentage of time within the normoglycemic range, defined as 70-180 mg/dL (3.9-10 mmol/L).

Results: Eighty-five participants were enrolled and randomized to study groups with 43 participants in the intervention (CGM) group and 42 patients in the control (standard of care) group. For the primary outcome, there was no statistically significant difference between the intervention group (mean = 60.5%, SD = 30.5) and the control group (mean = 61.4%, SD = 28.3) in time within the goal glucose range (mean difference -0.9%, 95% CI -13.6 to 11.8, p = .9). Except for patient satisfaction, there were no statistically significant differences between groups for secondary and exploratory outcomes.

Interpretation: The results of this study do not support CGM as a superior method for routine glucose monitoring in the intensive care unit compared to standard of care.

Trial registry: This study was registered with ClinicalTrials.gov (NCT05442853).

Background: Previous clinical data suggest that the presence of a pleural effusion is associated with poor survival. However, these studies were limited by either a small sample size or lack of an adequate control group.

Research questions: What is the impact of pleural effusion on survival in patients hospitalized with an admitting diagnosis of the three most common etiologies of pleural effusion: Cancer, congestive heart failure or pneumonia?

Study design and methods: This is a retrospective analysis of US veterans hospitalized between January 1^st,2000 to December 31^st,2020. International classification of disease codes were used to identify patients with an admitting diagnosis of congestive heart failure (CHF), pneumonia, or cancer. Patients were dichotomized as having a clinically significant pleural effusion (PE) when a pleural effusion drainage was performed or not (NO-PE). All-cause mortality was compared between the PE and NO-PE cohort.

Results: We analyzed 34,707 patients in the PE group and 792,217 patients in the NO-PE group. Patients with PE had a significantly higher all-cause mortality compared to patients with NO-PE. The median survival time was significantly lower in PE group as compared to NO-PE group across all three diagnosis, CHF (PE: 1.51 years; 95% CI: 1.40-1.61 vs NO-PE: 3.23 years; 95% CI: 3.21-3.26), Cancer (PE:1.33 years; 95% CI 1.27,1.39 vs NO-PE: 2.05 years; 95% CI:2.02-2.08) and pneumonia (PE: 4.27 years; 95% CI: 3.94-4.61 vs NO-PE: 5.11 years, 95% CI: 5.06-5.15). The hazard ratio of all-cause mortality remained unchanged after adjusting for demographics and comorbidities.

Interpretation: The presence of a clinically significant pleural effusion was independently associated with higher all-cause mortality in patients with admitting diagnosis of CHF, cancer and pneumonia. Clinicians and researchers should consider the association of CHF, cancer, and pneumonia with pleural effusions when estimating the prognosis of individual patients and when assessing the survival of longitudinal cohorts.

Background: Preserved ratio impaired spirometry (PRISm) is heterogeneous and includes restrictive lung disease. Interstitial lung abnormalities (ILA) may represent early interstitial lung disease. The relationship between PRISm and ILA is not well understood.

Research question: What is the prevalence of ILA in PRISm compared to normal spirometry, what are risk factors for ILA within PRISm, and how do ILAs modify the association of PRISm and mortality?

Study design and methods: In COPDGene participants with baseline spirometry and chest computed tomography (CT) scans, we examined those with normal spirometry (FEV₁ ≥ 80% predicted and FEV₁/FVC ≥ 0.7) and PRISm (FEV₁ < 80% predicted with FEV₁/FVC ratio ≥ 0.7) with and without ILA, per Fleischner Society guidelines. We used logistic regression to examine the odds of ILA in PRISm. We modeled all-cause mortality with Cox regression. We evaluated the association of baseline ILA status on change in spirometry at followup.

Results: We included 4,494 normal spirometry and 1,262 PRISm participants. ILAs were present in 93 (7%) participants with PRISm, and 180 (4%) participants with normal spirometry. PRISm was associated with increased odds (1.74, 95% CI 1.33-2.27, p < 0.001) of ILA compared with normal spirometry. Among participants with PRISm, older age, increased smoke exposure, lower lung function, and increased airway wall thickness were associated with ILA. ILAs were associated with increased mortality (adj. HR 2.58, [95%CI:1.49-4.45]).

Interpretation: Within PRISm, ILA is associated with increased all-cause mortality, as well as increased age, smoke exposure, lower lung function, and increased airway wall thickness.

Effective bidirectional communication is crucial during end-of-life decision-making, which requires clear understanding between clinicians and patients/family members about treatment options, preferences, and goals of care. For those who have a non-English language preference (NELP), or who have difficulty speaking, reading, writing, and understanding English, interpreters are essential. However, patients who speak rarer languages, known as languages of lesser diffusion (LLDs), such as Karen spoken in Thailand and Myanmar, face unique challenges due to limited interpretation resources. In this work we discuss the case of a Karen-speaking patient admitted to the ICU who lacked decision-making capacity, requiring the involvement of family members who also spoke Karen, for a code status discussion. Despite efforts to find an interpreter, no Karen interpreter was initially available, complicating the communication and decision-making about changing the code status to DNR/DNI. A remote Karen interpreter was later identified allowing for effective communication, and clinician assurance that the family did understand the implications of their decision and had made it voluntarily. End-of-life decision-making is complex and challenging, requiring culturally sensitive communication. Patients who speak LLDs face unique difficulties in these discussions compared to those who speak more common languages due to lack of interpretation resources. The purpose of this case report is to draw attention to these specific challenges and explore ethical concerns when engaging in decision-making conversations with patients and families who speak a LLD.

Background: Pediatric pulmonary hypertension (PH) is a severe incurable disease with poor prognosis. In pediatric PH, trial design is hampered by the absence of age-appropriate trial endpoints. This study evaluated physical activity (PA) measured by hip-anchored accelerometry as a potential trial endpoint in pediatric PH.

Research questions: Is PA-accelerometry associated with disease severity, and based on this association, what minimal important differences (MIDs) correspond to meaningful changes in disease severity in pediatric PH?

Study design and methods: Accelerometer outputs from 54 children with hemodynamically confirmed PH were analyzed. Univariable linear regression and mixed effect models were respectively used for cross sectional and longitudinal analyses 1) to evaluate the association between Z-scores of PA-accelerometry counts per minute (CPM-Z) and of % of time spent in moderate or vigorous physical activity (%MVPA-Z) and disease severity indices 6-minute walk-distance Z-scores (6MWD-Z), World Health Organization functional class (WHO-FC), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and tricuspid annular plane systolic excursion Z-scores (TAPSE-Z) and 2) to perform anchor-based MID estimations for CPM-Z and %MVPA-Z, using defined clinical functional impairment levels (6MWD-Z and WHO-FC) as reference anchors.

Results: When assessing the association between disease severity and PA-accelerometry cross-sectionally, we found significant associations between CPM-Z and WHO-FC, 6MWD-Z and NT-proBNP. %MVPA-Z was significantly associated with WHO-FC and 6MWD-Z. In longitudinal analysis, these associations were confirmed throughout the disease course. MID estimations, expressed in Z-score units, resulted in mean MIDs of 0.3-0.4 CPM-Z when anchored to 6MWD-Z, 0.7 CPM-Z when anchored to WHO-FC, 0.4-0.5 %MVPA-Z when anchored to 6MWD-Z and 0.5-0.6 %MVPA-Z when anchored to WHO-FC.

Interpretation: This study underscores the robust relationship between PA-accelerometry and disease severity in children with PH and fills a critical gap in pediatric PH trial design and evaluation of treatment efficacy by providing anchor-based MID-estimates for hip-anchored PA-accelerometry.

High flow nasal cannula (HFNC) is a first-line therapy for patients with acute respiratory failure. Despite increased HFNC utilization over recent years -accelerated in part by the Coronavirus Disease 2019 pandemic - high-quality evidence to guide HFNC discontinuation is lacking. Decisions about when and how quickly to reduce flow rate, fraction of inspired oxygen, or both simultaneously are frequently left to clinicians' discretion without clear guidance on an optimal approach. Failure to de-escalate HFNC support when clinically appropriate has many potential consequences, such as prolongation of ICU/hospital length of stay, increased healthcare costs, and reduced availability of limited hospital resources. With the goal of improving care efficiency and resource utilization among hospitalized patients with acute respiratory failure, we propose a standardized approach for HFNC discontinuation focused on "liberation" (similar to spontaneous breathing trials (SBTs) for patients undergoing mechanical ventilation) using a stepwise approach guided by physiology.

Background: The cuff leak test (CLT) is an important tool to assess the risk of upper airway obstruction after extubation.

Research question: Does modified CLT approach have superior ability in predicting re-intubation compared with traditional method?

Study design and methods: This was a prospective, multicenter, randomized control trial. The primary end point was the incidence of the need for reintubation within 48 h after extubation. The secondary end points were the actual incidence of reintubation, the incidence of post-extubation stridor (PES), and the duration of invasive mechanical ventilation (IMV), etc. RESULT: There were totally 536 patients randomized to either modified CLT group (n = 268) or control group (n = 268). The incidence of reintubation within 48 h after extubation did not differ between the groups. PES within 24 h after extubation was more frequent in the modified CLT group than in the control group (5.22% vs. 1.49%; OR 0.275 [95% CI, 0.089-0.846]; P = 0.028). The IMV duration was shorter in the modified CLT group than in the control group (137 h [74, 218] vs. 159 h [95, 252]; OR 1.001 [95% CI, 1.000-1.002], P = 0.046). In the patients with IMV duration ≥6 days, the incidence of PES was 2.95% in modified CLT group and 0.74% in the control group (OR 0.203 [95% CI, 0.042-0.975], P = 0.048).

Interpretation: Compared with the control group, the modified CLT approach might better predict PES within 24 h after extubation, especially for the patients with IMV duration longer than 6 days, but it could not help decrease the reintubation incidence and mortality.

Clinicaltrials: GOV: NCT05550220, Registered 19 September 2022.

Background: There is an ongoing debate about whether clearance of Mycobacterium tuberculosis infection occurs and at what magnitude. Recent studies quantifying 'uncertainty zones' of interferon-gamma release assays (IGRA) provide a more stringent estimate of reversion, potentially indicating clearance.

Research question: When accounting for 'uncertainty zones' through stringent cutoffs, what are the trajectories of interferon-gamma release assays in cases of Mycobacterium tuberculosis infection?

Study design and methods: We followed five cohorts from South Africa, China, Tanzania, and the United States tested with an IGRA test three or more times for stringent conversion and reversion. The annual risk of IGRA reversion was assessed after an IGRA conversion and among those with baseline positivity.

Results: 26,596 IGRA measurements were taken over 13,593 years of follow-up (N_participants=7,683). Stringent reversion at year 2 after stringent conversion at year 1 varied between cohorts, occurring in 48% (43/90) for WANTAI, 37% (22/59) for QuantiFERON, and 17% (2/12) for T-SPOT.TB, respectively. In the U.S. cohorts, stringent reversion at year 1 after stringent conversion at 6 months was 58% (15/26) for QuantiFERON and 18% (12/60) for T-SPOT.TB. Stringent reversion at 1 year after baseline positivity occurred in 12% (47/404) for WANTAI, 21% (10/48) for QuantiFERON and 44% for T-SPOT.TB (45/102). In one cohort from (N=399; age range, 59 years [IQR, 48-67]), IGRA reversion was more common in younger participants (Adjusted Odds Ratio [aOR], 0.95; 95% CI, 0.93-0.97) and those without recent close tuberculosis exposure (aOR, 0.35; 95%CI, 0.11-1.03 in South Africa; 0.10; 95%CI, 0.01-0.61 in China).

Interpretation: These results suggest high annual rates of IGRA reversion, even with the use of 'uncertainty zones'; reversion rates decreased with time from exposure and at older ages.

Background: Preserved ratio impaired spirometry (PRISm) and restrictive spirometric pattern (RSP) are often considered interchangeable in identifying restrictive impairment in spirometry.

Research question: Do PRISm and RSP have different individual associations with risk factors, morbidity, and mortality?

Study design and methods: In a cross-sectional and longitudinal study, including 26,091 Norwegian general population men (30 to 46 years of age), we explored the association of PRISm and RSP with smoking habits, BMI, education, respiratory symptoms, self-reported cardiopulmonary disease, and mortality after 26 years of follow-up. PRISm was defined as FEV₁/FVC ≥ lower limit of normal (LLN) and FEV₁ < LLN, and RSP was defined as FEV₁/FVC ≥ LLN and FVC < LLN. We compared the associations of PRISm and RSP to airflow obstruction and normal spirometry, both as mutually (PRISm alone, RSP alone) and nonmutually exclusive (PRISm, RSP) categories, adjusting for age, BMI, smoking, and education. We also conducted sensitivity analyses using Global Initiative for Chronic Obstructive Lung Disease criteria to define spirometric abnormalities.

Results: The prevalence of the mutually exclusive spirometric patterns was as follows: normal 82.4%, obstruction 11.0%, PRISm alone 1.4%, RSP alone 1.7%, and PRISm + RSP 3.5%. PRISm alone patients frequently had obesity (11.2%) and had active or previous tobacco use, commonly reporting cough, phlegm, wheeze, asthma, and bronchitis. RSP alone patients had both obesity (14.6%) and underweight (2.9%), with increased breathlessness, but similar smoking habits to patients with normal spirometry. The prevalence of heart disease was 4.6% in PRISm alone, 2.7% in RSP alone, and 1.6% in obstruction. With normal spirometry as a reference, RSP alone had increased all-cause (hazard ratio [HR], 1.57; 95% CI, 1.21-2.04), cardiovascular (HR, 1.48; 95% CI, 0.88-2.48), diabetes (HR, 6.43; 95% CI, 1.88-21.97), and cancer (excluding lung) mortality (HR, 1.51; 95% CI, 0.95-2.42). PRISm alone had increased respiratory disease mortality (HR, 4.00; 95% CI, 1.22-13.16). Patients with PRISm + RSP had intermediate characteristics and the worst prognosis. Findings were overall confirmed with nonmutually exclusive categories and Global Initiative for Chronic Obstructive Lung Disease criteria.

Interpretation: Our findings indicate that PRISm and RSP are spirometric patterns with distinct risk factors, morbidity, and mortality, which should be differentiated in future studies.