Incidence of post-operative delirium increases as severity of frailty increases.

OBJECTIVE: The surgical population is ageing and often frail. Frailty increases the risk for poor post-operative outcomes such as delirium, which carries significant morbidity, mortality and cost. Frailty is often measured in a binary manner, limiting pre-operative counselling. The goal of this study was to determine the relationship between categorical frailty severity level and post-operative delirium. METHODS: We performed an analysis of a retrospective cohort of older adults from 12 January 2018 to 3 January 2020 admitted to a tertiary medical center for elective surgery. All participants underwent frailty screening prior to inpatient elective surgery with at least two post-operative delirium assessments. Planned ICU admissions were excluded. Procedures were risk-stratified by the Operative Stress Score (OSS). Categorical frailty severity level (Not Frail, Mild, Moderate, and Severe Frailty) was measured using the Edmonton Frail Scale. Delirium was determined using the 4 A's Test and Confusion Assessment Method-Intensive Care Unit. RESULTS: In sum, 324 patients were included. The overall post-operative delirium incidence was 4.6% (15 individuals), which increased significantly as the categorical frailty severity level increased (2% not frail, 6% mild frailty, 23% moderate frailty; P < 0.001) corresponding to increasing odds of delirium (OR 2.57 [0.62, 10.66] mild vs. not frail; OR 12.10 [3.57, 40.99] moderate vs. not frail). CONCLUSIONS: Incidence of post-operative delirium increases as categorical frailty severity level increases. This suggests that frailty severity should be considered when counselling older adults about their risk for post-operative delirium prior to surgery.

Relationship Between Posttraumatic Headache and Depression After Mild Traumatic Brain Injury.

OBJECTIVES: Mild traumatic brain injury (mTBI) can lead to psychiatric and somatic symptoms for some patients, including posttraumatic headache (PTH) and depression. This study attempted to further establish the relationship between PTH and depression following mTBI and investigate whether the presence of PTH immediately following injury can identify patients at risk for developing depressive symptoms up to 6 months later. METHODS: This study was a secondary analysis of data from Head Injury Serum Markers for Assessing Response to Trauma (HeadSMART), a prospective study of adult patients in the emergency department with head injury. Participants included 265 patients who met criteria for mTBI and completed the Rivermead Post-Concussion Symptoms Questionnaire, to identify PTH within 24 hours after injury, and the Patient Health Questionnaire-9, to assess depressive symptoms during follow-up. Measures were completed at the initial visit immediately after the injury in the emergency department and at 1-, 3-, and 6-month follow-up visits. RESULTS: Patients with acute PTH (aPTH) at time of injury were more likely to report PTH at 1, 3, and 6 months. They also had more severe depressive symptoms and a greater likelihood of clinically significant depression at all time points. CONCLUSIONS: Patients with aPTH within 24 hours after injury were more likely to report continued symptoms of PTH and clinically significant depression at 1, 3, and 6 months. These findings provide support for using the presence of aPTH in the emergency department following mTBI as an indicator for monitoring persistent PTH and depressive symptoms in the postacute recovery period.

Efficacy of Ultrasound for the Detection of Possible Fatty Liver Disease in Children.

Pediatric MASLD (previously referred to as NAFLD) incidence has continued to rise along with the obesity pandemic. Pediatric MASLD increases the risk of liver fibrosis and cirrhosis in adulthood. Early detection and intervention can prevent and reduce complications. Liver biopsy remains the gold standard for diagnosis, although imaging modalities are increasingly being used. We performed a retrospective study of 202 children seen in a pediatric gastroenterology clinic with a complaint of abdominal pain, elevated liver enzymes or MASLD, or a combination of the three to evaluate screening methods for MASLD. A total of 134 of the 202 patients included in the study underwent laboratory testing and abdominal ultrasound. Ultrasound images were reviewed with attention to liver size and echotexture by a fellowship-trained pediatric radiologist for liver size and echotexture. Overall, 76.2% of the initial radiology reports correctly identified hepatomegaly based on age and 75.4% of the initial radiology reports correctly described hepatic echogenicity that was consistent with increased hepatic fat deposition. Use of screening ultrasound in concert with other clinical evaluations can be helpful to identify children at risk of MASLD. Utilizing ranges for liver span according to age can help to diagnose hepatomegaly, and understanding how to identify hepatic echogenicity is important for identifying possible hepatic steatosis.

Lung Protective Ventilation Adherence and Outcomes for Patients With COVID-19 Acute Respiratory Distress Syndrome Treated in an Intermediate Care Unit Repurposed to ICU Level of Care.

OBJECTIVE: During the COVID-19 pandemic, some centers converted intermediate care units (IMCUs) to COVID-19 ICUs (IMCU/ICUs). In this study, we compared adherence to lung protective ventilation (LPV) and outcomes for patients with COVID-19-related acute respiratory distress syndrome (ARDS) treated in an IMCU/ICU versus preexisting medical ICUs (MICUs). DESIGN: Retrospective observational study using electronic medical record data. SETTING: Two academic medical centers from March 2020 to September 2020 (period 1) and October 2020 to May 2021 (period 2), which capture the first two COVID-19 surges in this health system. PATIENTS: Adults with COVID-19 receiving invasive mechanical ventilation who met ARDS oxygenation criteria (Pao2/Fio2 ≤ 300 mm Hg or Spo2/Fio2 ≤ 315). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined LPV adherence as the percent of the first 48 hours of mechanical ventilation that met a restrictive definition of LPV of, tidal volume/predicted body weight (Vt/PBW) less than or equal to 6.5 mL/kg and plateau pressure (Pplat) less than or equal to 30 cm H2o. In an expanded definition, we added that if Pplat is greater than 30 cm H2o, Vt/PBW had to be less than 6.0 mL/kg. Using the restricted definition, period 1 adherence was lower among 133 IMCU/ICU versus 199 MICU patients (92% [95% CI, 50-100] vs. 100% [86-100], p = 0.05). Period 2 adherence was similar between groups (100% [75-100] vs. 95% CI [65-100], p = 0.68). A similar pattern was observed using the expanded definition. For the full study period, the adjusted hazard of death at 90 days was lower in IMCU/ICU versus MICU patients (hazard ratio [HR] 0.73 [95% CI, 0.55-0.99]), whereas ventilator liberation by day 28 was similar between groups (adjusted subdistribution HR 1.09 [95% CI, 0.85-1.39]). CONCLUSIONS: In patients with COVID-19 ARDS treated in an IMCU/ICU, LPV adherence was similar to, and observed survival better than those treated in preexisting MICUs. With adequate resources, protocols, and staffing, IMCUs provide an effective source of additional ICU capacity for patients with acute respiratory failure.

Pulmonary sarcoidosis: differences in lung function change over time.

INTRODUCTION: Given the heterogeneity of sarcoidosis, predicting disease course of patients remains a challenge. Our aim was to determine whether the 3-year change in pulmonary function differed between pulmonary function phenotypes and whether there were differential longitudinal changes by race and sex. METHODS: We identified individuals seen between 2005 and 2015 with a confirmed diagnosis of sarcoidosis who had at least two pulmonary function test measurements within 3 years of entry into the cohort. For each individual, spirometry, diffusion capacity, Charlson Comorbidity Index, sarcoidosis organ involvement, diagnosis duration, tobacco use, race, sex, age and medications were recorded. We compared changes in pulmonary function by type of pulmonary function phenotype and for demographic groups. RESULTS: Of 291 individuals, 59% (173) were female and 54% (156) were black. Individuals with restrictive pulmonary function phenotype had significantly greater 3-year rate of decline of FVC% (forced vital capacity) predicted and FEV1% (forced expiratory volume in 1 s) predicted course when compared with normal phenotype. We identified a subset of individuals in the cohort, highest decliners, who had a median 3-year FVC decline of 156 mL. Black individuals had worse pulmonary function at entry into the cohort measured by FVC% predicted, FEV1% predicted and diffusing capacity for carbon monoxide % predicted compared with white individuals. Black individuals' pulmonary function remained stable or declined over time, whereas white individuals' pulmonary function improved over time. There were no sex differences in rate of change in any pulmonary function parameters. SUMMARY: We found significant differences in 3-year change in pulmonary function among pulmonary function phenotypes and races, but no difference between sexes.

Extended Versus Standard Proning Duration for COVID-19 Associated Acute Respiratory Distress Syndrome: A Target Trial Emulation Study.

RATIONALE: Prone positioning for > 16 hours in moderate-to-severe acute respiratory distress syndrome (ARDS) improves survival. However, the optimal duration of proning is unknown. OBJECTIVE: To estimate the effect of extended versus standard proning duration on patients with moderate-to-severe COVID-19 ARDS. METHODS: Data were extracted from a 5-hospital electronic medical record registry. Patients who were proned within 72 hours of mechanical ventilation were categorized as receiving extended (> 24 hours) versus standard (16-24 hours) proning based on the first proning session length. We used a target trial emulation design to estimate the effect of extended vs. standard proning on the primary outcome of 90-day mortality, and secondary outcomes of ventilator liberation and ICU discharge. Analytically we used inverse probability of treatment weighted (IPTW) Cox, or Fine and Gray regression models. RESULTS: 314 patients were included, 234 who received extended proning, and 80 who received standard duration. Extended proning patients were older, had greater comorbidity, were more often at an academic hospital, and had shorter time from admission to mechanical ventilation. After IPTW, characteristics were well balanced. Unadjusted 90-day mortality in the extended vs. standard proning groups was 39% vs 58%. In doubly-robust IPTW analyses, we found no significant effects of extended vs. standard proning duration on mortality (hazard ratio [95% CI] 0.95 [0.51-1.77]), ventilator liberation (sub-distribution hazard [sHR] 1.60, [0.97-2.64], or ICU discharge (sHR 1.31 [0.82-2.10]). CONCLUSION: Using target trial emulation, we found no significant effect of extended vs. standard proning duration on mortality, ventilator liberation, or ICU discharge. However, given the imprecision of estimates, further study is justified. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Delirium in the United States: Results From the 2023 Cross-Sectional World Delirium Awareness Day Prevalence Study.

BACKGROUND: Delirium is an acute brain dysfunction associated with an increased risk of mortality and future dementia. OBJECTIVES: To describe the prevalence of clinically documented delirium in the United States on World Delirium Awareness Day 2023. METHODS: This is a sub-analysis of a prospective, cross-sectional, online, international survey. All health care settings were eligible, with the exception of operating rooms and outpatient clinics. Health care clinicians, administrators, and researchers completed the survey. The primary outcome was the prevalence of clinically documented delirium at 8:00 a.m. and 8:00 p.m. on March 15, 2023. Secondary outcomes were related to health care delivery. Descriptive statistics are reported. Differences between unit types (non-intensive care unit vs intensive care unit) were examined for all outcomes. RESULTS: Ninety-one hospital units reported on 1318/1213 patients. The prevalence of clinically documented delirium was 16.4% (n = 216/1318) at 8:00 a.m. and 17.9% (n = 217/1213) at 8:00 p.m. (P = 0.316) and significantly differed between age groups, reported discipline, unit, and hospital types. Significant differences were identified between non-intensive care unit and intensive care unit settings in the use of delirium-related protocols, nonpharmacologic and pharmacologic management, educational processes, and barriers to evidence-based delirium care. CONCLUSIONS: To our knowledge, this is the first epidemiologic survey of clinically documented delirium across two time points in the United States. Delirium remains a significant burden and challenge for health care systems. The high percentage of units using delirium management protocols suggests administrator and clinician awareness of evidence-based strategies for its detection and mitigation. We provide recommendations for future studies and quality improvement projects to improve clinical recognition and management of delirium.

Development and preliminary validation of the personalized cystic fibrosis medication questionnaire (PCF-MQ).

BACKGROUND: A personalized approach to assessing medication knowledge may identify opportunities for education to support self-management of cystic fibrosis (CF). This project describes the development, scoring, and preliminary validity of the Personalized CF Medication Questionnaire (PCF-MQ), designed to assess knowledge of prescribed CF medication purpose, administration, and dose and frequency. METHODS: Participants completed the PCF-MQ, the Knowledge of Disease Management (KDM-CF), and the Cystic Fibrosis-Medication Beliefs Questionnaire (CF-MBQ). Prescribed regimens were abstracted from medical records. Eligibility criteria were age 12 years and older, diagnosed with CF, and prescribed a CF medication. Statistical analyses were conducted using R software. Spearman rho was used to test correlations between measures. RESULTS: Sixty people with CF (pwCF) were enrolled; three people reported a regimen that substantially deviated from the medical record and were excluded from the analyses. The mean (SD) age was 20.2 (7.3) years, 54 % were female, and 74 % had a FEV1pp ≥70 %. The mean (SD) PCF-MQ total score was 77.8 (12.3) and knowledge scores ranged from a low of 58.3 for levalbuterol to 100 for ivacaftor. The PCF-MQ total score correlated with the KDM total score and subscales (Spearman Rho= 0.32-0.59, p < 0.05) and was not correlated with the CF-MBQ subscales (p > 0.05)). CONCLUSIONS: The PCF-MQ was correlated with another measure of general CF knowledge, but not health beliefs; because of the small sample size, this should be considered preliminary evidence of its validity. Advantages over existing CF knowledge measures include its practicality for use to help assess pwCF's knowledge about their prescribed regimen.

Clinician response after receipt of abnormal pediatric ambulatory blood pressure monitoring - characteristics associated with inertia and action.

BACKGROUND: Ambulatory Blood Pressure Monitoring (ABPM) is recommended for diagnosis and management of hypertension. We aimed to identify characteristics associated with physician action after receipt of abnormal findings. METHODS: This was a retrospective cross-sectional analysis of patients 5-22 years old who underwent 24-h ABPM between 2003-2022, met criteria for masked or ambulatory hypertension, and had a pediatric nephrology clinic visit within 2 weeks of ABPM. "Action" was defined as medication change/initiation, lifestyle or adherence counseling, evaluation ordered, or interpretation with no change. Characteristics of children with/without 1 or more actions were compared using Student t-tests and Chi-square. Regression analyses explored the independent association of patient characteristics with physician action. RESULTS: 115 patients with masked (n = 53) and ambulatory (n = 62) hypertension were included: mean age 13.0 years, 48% female, 38% Black race, 21% with chronic kidney disease, and 25% overweight/obesity. 97 (84%) encounters had a documented physician action. Medication change (52%), evaluation ordered (40%), and prescribed lifestyle change (35%) were the most common actions. Adherence counseling for medication and lifestyle recommendations were documented in 3% of encounters. 24-h, wake SBP load, and sleep DBP load were significantly higher among those with physician action. Patients with > 1 action had greater adiposity, SBP, and dipping. Neither age, obesity, nor kidney disease were independently associated with physician action. CONCLUSIONS: While most abnormal ABPMs were acted upon, 16% did not have a documented action. Greater BP load was one of the few characteristics associated with physician action. Of potential actions, adherence counseling was underutilized.

An international, multicenter, survey-based analysis of practice and management of acute liver failure.

Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and HE in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on the management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. A total of 267 physicians completed the survey, with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver-intensive or transplant-intensive care unit ( p < 0.001). The median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, 1 week in 37.6%, and more than 1 week in 9.6% ( p < 0.001). Deceased donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria, and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of patients with ALF, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring HE and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare, multicenter studies are valuable for identifying global practice.

Accuracy and Performance of Triage Blood Pressure Measurements in A Real-World Clinic Setting.

OBJECTIVES: To investigate the agreement and accuracy of triage blood pressure (BP) in a real-world clinic setting, compared with the reference standard. STUDY DESIGN: Paired triage and standardized BP measurements from patients 4 through 21 years old evaluated in an obesity-related hypertension clinic were obtained via chart-review. Triage BPs were measured by a medical assistant or nurse, often by automated device. Triplicate manual BPs were obtained by the clinic physician. Bland-Altman analyses determined mean differences between paired triage and mean standardized BPs. GEE-based multivariable relative risk (RR) regression determined the RR of triage BP overestimation by ≥ 5 mmHg. Overall agreement, sensitivity, specificity, positive predictive value, and negative predictive value of triage BP measurements identifying hypertensive BP were determined. RESULTS: One hundred thirty participants with 347 clinic encounters were included. Mean age was 13.3 years (SD 3.94), 76% were Black, and 58% were male. Overall mean systolic and diastolic BP difference was 8.7 mmHg (95% limits on agreement: -16.66, 34.07) and 4.1 mmHg (95% limits on agreement: -18.56, 26.68), respectively. Triage systolic BP was more likely overestimated by ≥ 5 mmHg when a large adult (RR = 1.49; 95% CI: 1.00, 2.21) or thigh cuff (RR = 1.94; 95% CI: 1.08, 3.51) was required compared with when a child/adult cuff was required. Overall agreement in identifying hypertensive BP was 57.6%. Sensitivity (52.6%), specificity (63.4%), positive predictive value (60.8%), and negative predictive value (55.3%) were low across all cuffs. CONCLUSIONS: There was poor agreement between usual triage and standardized BP measurements, with potential for significant clinical implications. CLINICAL TRIAL REGISTRATION: ReNEW Clinic Cohort Study (ReNEW), NCT03816462, https://clinicaltrials.gov/ct2/show/NCT03816462.

The effect of elexacaftor/tezacaftor/ivacaftor on non-pulmonary symptoms in adults with cystic fibrosis.

Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator that has led to large benefits in lung function, pulmonary exacerbation rates, and respiratory symptoms. Less is known about the effect of ETI on non-pulmonary symptoms. The objective of this study was to examine the changes in patient reported outcomes after starting ETI in multiple non-pulmonary symptoms. Methods: This was a prospective cohort study of adults with CF. Participants completed questionnaires prior to starting ETI and then at weeks 2, 4, 6, 8, 10, 12, and 14 after starting ETI. They completed the following validated instruments: PROMIS Pain Intensity, PROMIS Pain Interference, FACIT Fatigue, SNOT22, PAC-SYM, PHQ8, GAD7 and Pittsburgh Sleep Quality Index. Longitudinal changes for outcomes were modelled using linear regression based on general estimating equations. Results: 22 participants enrolled who answered questionnaires before and after starting ETI. The median age was 35.3 years (IQR 11.1) and 13 (59.1%) were male. In models adjusted for age, sex, and baseline value there were significant improvements in pain interference (ß = -2.57; 95% CI -4.92, -0.23), sinus symptoms (ß = -4.50; 95% CI -7.59, -1.41), and sleep disturbance (ß = -1.90; 95% CI -2.71, -1.09) over 14 weeks after starting ETI. No symptom areas worsened over the study period. Conclusions: In this prospective study we found statistically significant improvements in three different non-pulmonary symptom areas in people with CF started on ETI. While this was a small, uncontrolled study it suggests that use of highly effective CFTR modulators can result in benefits for patients beyond pulmonary symptoms.

Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells.

Bacillus Calmette-Guérin (BCG) confers heterologous immune protection against viral infections and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here, we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model. BCG vaccination conferred a modest reduction on lung SCV2 viral load, bronchopneumonia scores, and weight loss, accompanied by a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. BCG uniquely recruited immunoglobulin-producing plasma cells to the lung suggesting accelerated local antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, with a transcriptional shift away from exhaustion markers and toward antigen presentation and repair. Similarly, BCG enhanced recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, that show reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.

Indicators of Neighborhood-Level Socioeconomic Position and Pediatric Critical Illness.

BACKGROUND: With recent prioritization of equity in pediatric health outcomes, a shift to examine neighborhood-level health care disparities within pediatric populations has occurred, specifically in the context of critical illness. RESEARCH QUESTION: Does an association exist between individual indicators of neighborhood-level disadvantage and incidence of PICU admission? STUDY DESIGN AND METHODS: Pediatric patients younger than 18 years admitted to a PICU in a large urban tertiary pediatric hospital from January 1, 2016, through December 31, 2019, with a residential address in the city of Baltimore or Baltimore County on the day of admission were included in this ecological study. Demographic and clinical characteristics of children admitted to the PICU were summarized, with the primary outcome being PICU admission. Unadjusted negative binomial regression was used to examine the association between census tract-level PICU admissions and the previously described census tract-level indicators of neighborhood socioeconomic position. Regression models included an offset term for the population younger than 18 years for each census tract; results of models are reported as incidence rate ratios (IRRs) with corresponding 95% CIs. RESULTS: We identified 2,476 PICU admissions: 1,351 patients from the city of Baltimore (10.25 per 1,000 children) and 1,125 patients from Baltimore County (6.31 per 1,000 children). Most PICU admissions (n = 906 [68%]) for the city of Baltimore represented an area deprivation index (ADI) of > 60, whereas most Baltimore County PICU admissions (n = 919 [82.3%]) represented an ADI of < 60. At the neighborhood level, the percentage of families living below the poverty line was associated with greater incidence of PICU admission in the city of Baltimore (IRR, 1.09; 95% CI, 1.00-1.18) and Baltimore County (IRR, 1.19; 95% CI, 1.05-1.36). For every $10,000 increase in median household income, PICU admission rates dropped by 9% for the city of Baltimore (IRR, 0.91; 95% CI, 0.86-0.95) and Baltimore County (IRR, 0.91; 95% CI, 0.88-0.94). Neighborhoods with vacant housing units also were associated with a higher incidence of PICU admission in the city of Baltimore (IRR, 1.10; 95% CI, 1.01-1.21) and Baltimore County (IRR, 1.46; 95% CI, 1.21-1.77), as was a 10% increase in occupied homes without vehicles (city of Baltimore: IRR, 1.14; 95% CI, 1.07-1.21; Baltimore County: IRR, 1.23; 95% CI, 1.11-1.37). INTERPRETATION: Health outcomes of pediatric critical illness should be examined in the context of structural determinants of health, including neighborhood-level and environmental characteristics.

Patterns of early life somatic growth in infants and children with a history of chronic lung disease of prematurity.

OBJECTIVE: Preterm infants, and especially those with additional comorbidities, are at risk of early life growth failure, which may impact postnatal lung growth and attainment of peak lung function. However, little is known about the early life growth patterns of those with chronic lung disease. The goal of this study was to describe the patterns appreciated in this population and their association with certain clinical characteristics. STUDY DESIGN: Demographic, clinical characteristics, and somatic growth parameters between birth and 3 years were retrospectively reviewed for a cohort of children (n = 616) recruited from an outpatient pulmonary clinic. Group-based trajectory modeling was used to identify unique longitudinal trajectories for each growth parameter. Demographic and clinical characteristics were compared using nonparametric analysis. RESULTS: Four distinct trajectories were appreciated in all three somatic growth domains (weight, length, and weight-for-length), which demonstrated a sizable proportion of subjects with a z-score below zero at 36 months of age, suggesting that the traditional preterm paradigm of "catch-up" growth may not be accurate for this population. CONCLUSIONS: Children with a history of chronic lung disease begin life with somatic growth measurements well below their term peers and display heterogeneous patterns of weight and length growth through the first 3 years of life. Future studies should focus on further understanding the relationship between somatic growth and respiratory outcomes in this population, which will ideally allow for the use of somatic growth measures as surrogate markers to identify individuals at the highest risk of postnatal growth failure and poor respiratory outcomes.

Declining Use of Prone Positioning After High Initial Uptake in COVID-19 Adult Respiratory Distress Syndrome.

OBJECTIVES: Prone positioning for acute respiratory distress syndrome (ARDS) has historically been underused, but was widely adopted for COVID-19-associated ARDS early in the pandemic. Whether this successful implementation has been sustained over the first 3 years of the COVID-19 pandemic is unknown. In this study, we characterized proning use in patients with COVID-19 ARDS from March 2020 to December 2022. DESIGN: Multicenter retrospective observational study. SETTING: Five-hospital health system in Maryland, USA. PATIENTS: Adults with COVID-19 supported with invasive mechanical ventilation and with a P ao2 /F io2 ratio of less than or equal to 150 mm Hg while receiving F io2 of greater than or equal to 0.6 within 72 hours of intubation. INTERVENTIONS: None. MEASUREMENTS: We extracted demographic, clinical, and positioning data from the electronic medical record. The primary outcome was the initiation of proning within 48 hours of meeting criteria. We compared proning use by year with univariate and multivariate relative risk (RR) regression. Additionally, we evaluated the association of treatment during a COVID-19 surge period and receipt of prone positioning. MAIN RESULTS: We identified 656 qualifying patients; 341 from 2020, 224 from 2021, and 91 from 2022. More than half (53%) met severe ARDS criteria. Early proning occurred in 56.2% of patients in 2020, 56.7% in 2021, and 27.5% in 2022. This translated to a 51% reduction in use of prone positioning among patients treated in 2022 versus 2020 (RR = 0.49; 95% CI, 0.33-0.72; p < 0.001). This reduction remained significant in adjusted models (adjusted RR = 0.59; 95% CI, 0.42-0.82; p = 0.002). Treatment during COVID-19 surge periods was associated with a 7% increase in proning use (adjusted RR = 1.07; 95% CI, 1.02-1.13; p = 0.01). CONCLUSIONS: The use of prone positioning for COVID-19 ARDS is declining. Interventions to increase and sustain appropriate use of this evidence-based therapy are warranted.

Race-Specific Interpretation of Spirometry: Impact on the Lung Allocation Score.

Rationale: Interpretation of spirometry using race-specific reference equations may contribute to health disparities via underestimation of the degree of lung function impairment in Black patients. The use of race-specific equations may differentially affect patients with severe respiratory disease via the use of percentage predicted forced vital capacity (FVCpp) when included in the lung allocation score (LAS), the primary determinant of priority for lung transplantation. Objectives: To determine the impact of a race-specific versus a race-neutral approach to spirometry interpretation on the LAS among adults listed for lung transplantation in the United States. Methods: We developed a cohort from the United Network for Organ Sharing database including all White and Black adults listed for lung transplantation between January 7, 2009, and February 18, 2015. The LAS at listing was calculated for each patient under race-specific and race-neutral approaches, using the FVCpp generated from the Global Lung Function Initiative equation corresponding to each patient's race (race-specific) or from the Global Lung Function Initiative "other" (race-neutral) equation. Differences in LAS between approaches were compared by race, with positive values indicating a higher LAS under the race-neutral approach. Results: In this cohort of 8,982 patients, 90.3% were White and 9.7% were Black. The mean FVCpp was 4.4% higher versus 3.8% lower among White versus Black patients (P < 0.001) under a race-neutral compared with a race-specific approach. Compared with White patients, Black patients had a higher mean LAS under both a race-specific (41.9 vs. 43.9; P < 0.001) and a race-neutral (41.3 vs. 44.3; P < 0.001) approach. However, the mean difference in LAS under a race-neutral approach was -0.6 versus +0.6 for White versus Black patients (P < 0.001). Differences in LAS under a race-neutral approach were most pronounced for those in group B (pulmonary vascular disease) (-0.71 vs. +0.70; P < 0.001) and group D (restrictive lung disease) (-0.78 vs. +0.68; P < 0.001). Conclusions: A race-specific approach to spirometry interpretation has potential to adversely affect the care of Black patients with advanced respiratory disease. Compared with a race-neutral approach, a race-specific approach resulted in lower LASs for Black patients and higher LASs for White patients, which may have contributed to racially biased allocation of lung transplantation. The future use of race-specific equations must be carefully considered.

Early life growth trajectories in cystic fibrosis are associated with lung function at age six.

BACKGROUND: Higher growth percentiles are associated with more favorable lung function in cystic fibrosis (CF), prompting the creation of CF Foundation (CFF) nutritional guidelines. OBJECTIVES: To describe early childhood growth trajectories within CF, to determine if growth trajectories are associated with differences in lung function at age six, and to identify factors that differ between trajectory groups. METHODS: Retrospective cohort study of children diagnosed with CF and born 2000-2011 using the US CFF Patient Registry. Annualized growth parameters prior to age six were included in group-based trajectory modeling to identify unique early life growth trajectories. FEV1 percent predicted (FEV1pp) at age six was compared between trajectory groups using linear regression. Factors associated with group membership were identified using multinomial logistic regression. RESULTS: 6,809 children met inclusion criteria. Six discrete growth trajectories were identified, including three groups that began with growth parameters >50th percentile, termed: "always high", "gradual decliner", "rapid decliner", and three which began with growth parameters <50th percentile, termed: "rapid riser", "gradual riser", "always low". FEV1pp at age six was highest for the Always High trajectory. The Always Low trajectory was nearly 10% lower than the Always High trajectory. Sex, ethnicity, newborn screening and pancreatic function were associated with trajectory class membership. CONCLUSIONS: Distinct early life growth trajectories were identified within CF. Trajectories that met CFF nutritional guideline recommendations were associated with higher FEV1pp at age six. CF care teams should continue to partner with families to encourage interventions to support optimal growth to improve lung function in CF.

Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation.

STUDY OBJECTIVES: The major goal of the study was to determine whether changes in tongue morphology under selective hypoglossal nerve therapy for obstructive sleep apnea were associated with alterations in airway patency during sleep when specific portions of the hypoglossal nerve were stimulated. METHODS: This case series was conducted at the Johns Hopkins Sleep Disorders Center at Johns Hopkins Bayview Medical Center. Twelve patients with apnea implanted with a multichannel targeted hypoglossal nerve-stimulating system underwent midsagittal ultrasound tongue imaging during wakefulness. Changes in tongue shape were characterized by measuring the vertical height and polar dimensions between tongue surface and genioglossi origin in the mandible. Changes in patency were characterized by comparing airflow responses between stimulated and adjacent unstimulated breaths during non-rapid eye movement sleep. RESULTS: Two distinct morphologic responses were observed. Anterior tongue base and hyoid-bone movement (5.4 [0.4] to 4.1 [1.0] cm (median and [interquartile range]) with concomitant increases in tongue height (5.0 [0.9] to 5.6 [0.7] cm) were associated with decreases in airflow during stimulation. In contrast, comparable anterior hyoid movement (tongue protrusion from 5.8 [0.5] to 4.5 [0.9] cm) without significant increases in height (5.2 [1.6] to 4.6 [0.8] cm) were associated with marked increases in airflow during sleep. CONCLUSIONS: Tongue protrusion with preservation of tongue shape predicted increases in patency, whereas anterior movement with concomitant increases in height were associated with decreased pharyngeal patency. These findings suggest that pharyngeal patency can be best stabilized by stimulating lingual muscles that maintain tongue shape while protruding the tongue, thereby preventing it from prolapsing posteriorly during sleep. CITATION: Fleury Curado T, Pham L, Otvos T, et al. Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation. J Clin Sleep Med. 2023;19(5):947-955.

Heterogeneity of Lung Function Phenotypes in Sarcoidosis: Role of Race and Sex Differences.

Rationale: Historically, sarcoidosis was described as a restrictive lung disease, but several alternative phenotypes of pulmonary function have been observed. Pulmonary function phenotypes in sarcoidosis may represent different clinical and/or molecular phenotypes. Objectives: To characterize the prevalence of different pulmonary function phenotypes in a large and diverse sarcoidosis cohort from a tertiary care referral center. Methods: We identified individuals seen between 2005-2015 with a confirmed diagnosis of sarcoidosis. Data were collected from the first pulmonary function test (PFT) performed at our institution which included spirometry and diffusing capacity of the lung for carbon monoxide (DlCO). Demographics and clinical data were collected. Chi-squared analyses and multiple linear regressions were done to assess statistical differences and associations. Global Lung Function Initiative equations were used to calculate percent predicted measurements for spirometry and DlCO. Results: Of 602 individuals with sarcoidosis, 93% (562) had pulmonary involvement, 64% (385) were female, and 57% (341) were Black. Of those with pulmonary involvement, 56% had abnormal pulmonary function. Lung function impairment phenotypes included: 47% restriction, 22% obstruction, 15% isolated reduction in DlCO, and 16% combined obstructive restrictive phenotype. Restriction was the most common PFT phenotype among Black individuals (41%), while no lung impairment was most common among White individuals (66%) (P < 0.001). Males more frequently had obstruction (19%) compared with females (9%) P = 0.001, and females had more restriction (30%) compared with males (21%) P = 0.031. Conclusions: Among individuals with sarcoidosis and pulmonary function impairment, less than half demonstrated a restrictive phenotype. There were significant differences in pulmonary function phenotypes by race and sex.