Faculty Bibliography

INTRODUCTION: Ventilatory ratio (VR) is a bedside index of impaired ventilation that can be used as a surrogate marker for pulmonary dead space fraction (VD/VT). Vasculopathy is hypothesized to increase VD/VT in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. The purpose of this study was to investigate associations between VR and markers of inflammation in critically ill COVID-ARDS patients.
METHOD(S): We conducted a retrospective study of patients admitted to an intensive care unit due to SARS-CoV-2 infection. All subjects required invasive mechanical ventilation and met the Berlin criteria for ARDS. Clinical lab values were collected at two timepoints: 2-8 hours after intubation (T1) and 2-24 hours before tracheostomy (T2). VR was split into high (VR>2) and low (VR< 2) groups. Comparisons were performed using student's t, Mann-Whitney, and z tests for difference in proportions with alpha=0.05.
RESULT(S): Of the 139 subjects enrolled at T1, 67 (48%) had high VR (>2), with an overall mean VR of 2.08. High VR was significantly associated with leukocyte count (WBC) (13.3 vs. 10.6 x10^9/L, p=0.004), and platelet count (284 vs 248 x10^9/L, p=0.003). There was no association between VR status and procalcitonin (p=0.08), d-dimer (p=0.73), fibrinogen (p=0.38), CRP (p=0.22), and ferritin (p=0.33). Since certain markers had non-Gaussian distributions, we determined threshold values. D-dimer over 500 ng/mL was associated with higher VR (2.3 vs. 1.8, p=0.004) and procalcitonin over 0.5 ng/mL was moderately associated with higher VR (2.2 vs 1.9, p=0.052). CRP >181 mug/mL (the median) and ferritin values >1.5x the upper limit of normal were not associated with VR (p=0.30 and p=0.26, respectively). To enrich the dataset, we pooled data from T1 and T2 and treated each as an independent sample. In this pooled analysis, high VR was associated with higher platelet count (282 vs. 253, p=0.046), and higher procalcitonin (3.464 vs. 0.964, p=0.032). There were no significant associations with VR and d-dimer (p=0.88), fibrinogen (p=0.54), CRP (p=0.20), and ferritin (p=0.76) in the pooled data.
CONCLUSION(S): Ventilatory ratio appears to be associated with higher levels of some inflammatory markers including WBC, platelets, d-dimer, and procalcitonin in COVID-ARDS patients

INTRODUCTION: Ventilatory ratio (VR) is a simple bedside index of carbon dioxide removal. VR correlates well with physiologic dead space fraction (VD/VT) and clinical outcomes in patients with acute respiratory distress syndrome (ARDS). We hypothesized that high VR would identify COVID-19 ARDS patients with higher risk for death and organ failure.
METHOD(S): We conducted a retrospective cohort study of patients admitted to a single hospital in New York, NY, USA from March-July 2020 who had PCR-confirmed SARS-CoV-2 infection, met the Berlin criteria for ARDS, and required tracheostomy for prolonged invasive mechanical ventilation (MV). MV parameters were collected 2-8 hours after intubation. Based on prior studies, a VR>2 was considered to be abnormally elevated. Comparisons were performed using the Wilcoxon rank-sum test or z-test for difference in proportions with alpha=0.05. The primary outcome was 30- day mortality and the secondary outcome was a composite endpoint of death or organ failure defined as requiring renal replacement or extracorporeal membrane oxygenation (ECMO) during the hospitalization.
RESULT(S): Of 139 subjects enrolled, 67 (48.2%) had a VR>2. Low and high VR groups had similar baseline characteristics, including age (mean 58 years, SD +/-15.2), body mass index (30.1+/-6.69 kg/m2), simplified acute physiology score II (35.4+/-12.4), sequential organ failure assessment (SOFA) score (5.7+/-2.5), and a 19-point review of systemic disease history. High VR was not significantly associated with mortality (OR 0.92, p=0.827). However, high VR was associated with increased risk for the composite endpoint (OR 1.96, p=0.049) and independently identified patients with a higher risk of organ failure (OR 2.03, p=0.047). High VR was also associated with longer hospital length-of-stay for subjects who survived to discharge (52 vs. 43, p=0.035), more MV-free days within the 30 days after intubation (3.2 vs. 1.8, p=0.029), and higher SOFA score at 10+/-4 days post-intubation (6.2 vs. 4.8, p=0.024).
CONCLUSION(S): Ventilatory ratio identifies COVID-ARDS ventilated patients with increased risk for organ failure requiring advanced intervention, as well as patients who may require prolonged mechanical ventilation and hospitalization

BACKGROUND & AIMS/OBJECTIVE:The septin 9 blood test is indicated for colorectal cancer screening in individuals who decline first-line tests, but participation in this context is unclear. We conducted a randomized controlled trial to compare reoffering colonoscopy and fecal immunochemical test (FIT) alone versus also offering the blood test among individuals who declined colonoscopy and FIT. METHODS:Screen-eligible Veterans aged 50-75 years who declined colonoscopy and FIT within the previous 6 months were randomized to letter and telephone outreach to reoffer screening with colonoscopy/FIT only (control), or additionally offering the blood test as a second-line option (intervention). The primary outcome was completion of any screening test within 6 months. The secondary outcome was completion of a full screening strategy within 6 months, including colonoscopy for those with a positive noninvasive test. RESULTS:Of 359 participants who completed follow-up, 9.6% in the control group and 17.1% in the intervention group completed any screening (7.5% difference; P = .035). Uptake of colonoscopy and FIT was similar in the 2 groups. The full screening strategy was completed in 9.0% and 14.9% in the control and intervention groups, respectively (5.9% difference; P = .084). CONCLUSIONS:Among individuals who previously declined colonoscopy and FIT, offering a blood test as a secondary option increased screening by 7.5% without decreasing uptake of first-line screening options. However, completion of a full screening strategy did not increase. These findings indicate that a blood test is a promising method to improve colorectal cancer screening, but obtaining a timely colonoscopy after a positive noninvasive test remains a challenge (ClincialTrials.gov number, NCT03598166).

Rationale: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is characterized by global developmental impairment and early-onset, refractory seizures. In a recent placebo-controlled study, ganaxolone reduced major motor seizure frequency (MMSF) in patients with CDD. Here we report further data at a minimum of 1-year in the open-label extension (OLE).
Method(s): Patients with CDD (aged 2-19 years) who completed the double-blind phase were eligible to receive ganaxolone in the OLE. Assessments included changes in MMSF from pre-randomization baseline to 3-month intervals in the OLE, responder rates (>=50% and >=75% MMSF reductions), Clinical Global Impression of Improvement (CGI-I), safety, and tolerability.
Result(s): Eighty-eight patients (87.1%; median age of 5; 79.5% female) continued into the OLE (101 were randomized to the double-blind study). Median baseline 28-day MMSF was 50.6. The 1-year retention rate was 70.5% with 26 discontinuations. At the time of analysis, 34 participants had discontinued due to lack of efficacy (n = 12), adverse event (n = 10), or withdrawal by caregiver (n = 10) as the most common reasons. During months 1-3, 4-6, 7-9, and 10-12, patients experienced a median reduction in MMSF of 24.7%, 32.1%, 30.0%, and 42.2%, respectively. During months 13-24, MMSF reductions ranged from 44.2% to 56.1%. At 1 year, 46.3% and 23.9% of patients experienced a >=50% and >=75% reduction in MMSF, respectively. In the OLE, clinicians and caregivers rated 60.6% and 72.5% of the patients, respectively, as improved at 1 year. The most commonly reported adverse events were seizure (22.7%), somnolence (20.5%), vomiting (18.2%), and pyrexia (17.0%). There was one death reported due to sepsis, but it was deemed unrelated to study treatment.
Conclusion(s): Reductions in MMSF at 1 year and beyond provide supportive evidence for the maintenance of effect of ganaxolone in seizures associated with CDD. Ganaxolone was generally well-tolerated in the OLE with safety findings consistent with the double-blind phase

PURPOSE/UNASSIGNED:With undergraduate medical education shifting to an integrated, student-centered approach, self-regulated learning (SRL) skills are critical for student success. Educational research holds that learning strategy effectiveness is context dependent. Our study aims to explore what strategies medical students use to support SRL when engaged in the specific context of an integrated, student-centered curriculum. APPROACH/UNASSIGNED:This study took place in two medical schools with integrated, student-centered curricula. Semi-structured interviews were conducted with first-year medical students from both schools, asking them to reflect on the learning strategies they used throughout their first year of medical school. Interview data was analyzed first deductively using the SRL framework and then inductively to understand the specific strategies being used. FINDINGS/UNASSIGNED:Students engaged in strategies to support SRL in ways that were unique to the integrated, student-centered context. We found that medical students developed strategies to plan for integration and building connections across material during all three phases of self-regulated learning. INSIGHTS/UNASSIGNED:By identifying specific tasks and behaviors students utilized during their first year of medical school, this study provides a roadmap that students and educators can use to help students become self-regulated learners.

Rationale & Objective: Acute kidney injury (AKI) is a heterogeneous clinical syndrome with varying causes, pathophysiology, and outcomes. We incorporated plasma and urine biomarker measurements to identify AKI subgroups (subphenotypes) more tightly linked to underlying pathophysiology and long-term clinical outcomes. Study Design: Multicenter cohort study. Setting & Participants: 769 hospitalized adults with AKI matched with 769 without AKI, enrolled from December 2009 to February 2015 in the ASSESS-AKI Study. Predictors: 29 clinical, plasma, and urinary biomarker parameters used to identify AKI subphenotypes. Outcome: Composite of major adverse kidney events (MAKE) with a median follow-up period of 4.7 years. Analytical Approach: Latent class analysis (LCA) and k-means clustering were applied to 29 clinical, plasma, and urinary biomarker parameters. Associations between AKI subphenotypes and MAKE were analyzed using Kaplan-Meier curves and Cox proportional hazard models. Results: Among 769 AKI patients both LCA and k-means identified 2 distinct AKI subphenotypes (classes 1 and 2). The long-term risk for MAKE was higher with class 2 (adjusted HR, 1.41 [95% CI, 1.08-1.84]; P = 0.01) compared with class 1, adjusting for demographics, hospital level factors, and KDIGO stage of AKI. The higher risk of MAKE among class 2 was explained by a higher risk of long-term chronic kidney disease progression and dialysis. The top variables that were different between classes 1 and 2 included plasma and urinary biomarkers of inflammation and epithelial cell injury; serum creatinine ranked 20th out of the 29 variables for differentiating classes. Limitations: A replication cohort with simultaneously collected blood and urine sampling in hospitalized adults with AKI and long-term outcomes was unavailable. Conclusions: We identify 2 molecularly distinct AKI subphenotypes with differing risk of long-term outcomes, independent of the current criteria to risk stratify AKI. Future identification of AKI subphenotypes may facilitate linking therapies to underlying pathophysiology to prevent long-term sequalae after AKI.

Competency-based medical education (CBME) is an outcomes-based approach to education and assessment that focuses on what competencies trainees need to learn in order to provide effective patient care. Despite this goal of providing quality patient care, trainees rarely receive measures of their clinical performance. This is problematic because defining a trainee's learning progression requires measuring their clinical performance. Traditional clinical performance measures (CPMs) are often met with skepticism from trainees given their poor individual-level attribution. Resident-sensitive quality measures (RSQMs) are attributable to individuals, but lack the expeditiousness needed to deliver timely feedback and can be difficult to automate at scale across programs. In this eye opener, the authors present a conceptual framework for a new type of measure - TRainee Attributable & Automatable Care Evaluations in Real-time (TRACERs) - attuned to both automation and trainee attribution as the next evolutionary step in linking education to patient care. TRACERs have five defining characteristics: meaningful (for patient care and trainees), attributable (sufficiently to the trainee of interest), automatable (minimal human input once fully implemented), scalable (across electronic health records [EHRs] and training environments), and real-time (amenable to formative educational feedback loops). Ideally, TRACERs optimize all five characteristics to the greatest degree possible. TRACERs are uniquely focused on measures of clinical performance that are captured in the EHR, whether routinely collected or generated using sophisticated analytics, and are intended to complement (not replace) other sources of assessment data. TRACERs have the potential to contribute to a national system of high-density, trainee-attributable, patient-centered outcome measures.

Background: The introduction of electronic workflows has allowed for the flow of raw uncontextualized clinical data into medical documentation. As a result, many electronic notes have become replete of "noise" and deplete clinically significant "signals." There is an urgent need to develop and implement innovative approaches in electronic clinical documentation that improve note quality and reduce unnecessary bloating. Objective: This study aims to describe the development and impact of a novel set of templates designed to change the flow of information in medical documentation. Methods: This is a multihospital nonrandomized prospective improvement study conducted on the inpatient general internal medicine service across 3 hospital campuses at the New York University Langone Health System. A group of physician leaders representing each campus met biweekly for 6 months. The output of these meetings included (1) a conceptualization of the note bloat problem as a dysfunction in information flow, (2) a set of guiding principles for organizational documentation improvement, (3) the design and build of novel electronic templates that reduced the flow of extraneous information into provider notes by providing link outs to best practice data visualizations, and (4) a documentation improvement curriculum for inpatient medicine providers. Prior to go-live, pragmatic usability testing was performed with the new progress note template, and the overall user experience was measured using the System Usability Scale (SUS). Primary outcome measures after go-live include template utilization rate and note length in characters. Results: In usability testing among 22 medicine providers, the new progress note template averaged a usability score of 90.6 out of 100 on the SUS. A total of 77% (17/22) of providers strongly agreed that the new template was easy to use, and 64% (14/22) strongly agreed that they would like to use the template frequently. In the 3 months after template implementation, general internal medicine providers wrote 67% (51,431/76,647) of all inpatient notes with the new templates. During this period, the organization saw a 46% (2768/6191), 47% (3505/7819), and 32% (3427/11,226) reduction in note length for general medicine progress notes, consults, and history and physical notes, respectively, when compared to a baseline measurement period prior to interventions. Conclusions: A bundled intervention that included the deployment of novel templates for inpatient general medicine providers significantly reduced average note length on the clinical service. Templates designed to reduce the flow of extraneous information into provider notes performed well during usability testing, and these templates were rapidly adopted across all hospital campuses. Further research is needed to assess the impact of novel templates on note quality, provider efficiency, and patient outcomes.

Background: Few prospective studies of Long COVID risk factors have been conducted. The purpose of this study was to determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with Long COVID. Methods: In March 26, 2020, the COVID-19 Citizen Science study, an online cohort study, began enrolling participants with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection. Adult participants who reported a positive SARS-CoV-2 test result before April 4, 2022 were surveyed for Long COVID symptoms. The primary outcome was at least 1 prevalent Long COVID symptom greater than 1 month after acute infection. Exposures of interest included age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, variant wave, number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, and exercise. Results: Of 13 305 participants who reported a SARS-CoV-2 positive test, 1480 (11.1%) responded. Respondents' mean age was 53 and 1017 (69%) were female. Four hundred seventy-six (32.2%) participants reported Long COVID symptoms at a median 360 days after infection. In multivariable models, number of acute symptoms (odds ratio [OR], 1.30 per symptom; 95% confidence interval [CI], 1.20-1.40), lower socioeconomic status/financial insecurity (OR, 1.62; 95% CI, 1.02-2.63), preinfection depression (OR, 1.08; 95% CI, 1.01-1.16), and earlier variants (OR = 0.37 for Omicron compared with ancestral strain; 95% CI, 0.15-0.90) were associated with Long COVID symptoms. Conclusions: Variant wave, severity of acute infection, lower socioeconomic status, and pre-existing depression are associated with Long COVID symptoms.