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Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, one of the most common reasons for infection-related death worldwide. Causes of CAP include numerous viral, bacterial, and fungal pathogens, though frequently no specific organism is found. Beginning in 2019, the COVID-19 pandemic has caused incredible morbidity and mortality. COVID-19 has many features typical of CAP such as fever, respiratory distress, and cough, and can be difficult to distinguish from other types of CAP. Here, we highlight unique clinical features of COVID-19 pneumonia such as olfactory and gustatory dysfunction, lymphopenia, and distinct imaging appearance.

BackgroundLarge language models such as ChatGPT can produce increasingly realistic text, with unknown information on the accuracy and integrity of using these models in scientific writing.MethodsWe gathered ten research abstracts from five high impact factor medical journals (n=50) and asked ChatGPT to generate research abstracts based on their titles and journals. We evaluated the abstracts using an artificial intelligence (AI) output detector, plagiarism detector, and had blinded human reviewers try to distinguish whether abstracts were original or generated.ResultsAll ChatGPT-generated abstracts were written clearly but only 8% correctly followed the specific journal’s formatting requirements. Most generated abstracts were detected using the AI output detector, with scores (higher meaning more likely to be generated) of median [interquartile range] of 99.98% [12.73, 99.98] compared with very low probability of AI-generated output in the original abstracts of 0.02% [0.02, 0.09]. The AUROC of the AI output detector was 0.94. Generated abstracts scored very high on originality using the plagiarism detector (100% [100, 100] originality). Generated abstracts had a similar patient cohort size as original abstracts, though the exact numbers were fabricated. When given a mixture of original and general abstracts, blinded human reviewers correctly identified 68% of generated abstracts as being generated by ChatGPT, but incorrectly identified 14% of original abstracts as being generated. Reviewers indicated that it was surprisingly difficult to differentiate between the two, but that the generated abstracts were vaguer and had a formulaic feel to the writing.ConclusionChatGPT writes believable scientific abstracts, though with completely generated data. These are original without any plagiarism detected but are often identifiable using an AI output detector and skeptical human reviewers. Abstract evaluation for journals and medical conferences must adapt policy and practice to maintain rigorous scientific standards; we suggest inclusion of AI output detectors in the editorial process and clear disclosure if these technologies are used. The boundaries of ethical and acceptable use of large language models to help scientific writing remain to be determined.

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in

Objective To understand the perspectives of persons’ living with diabetes about the increasing cost of diabetes management through an analysis of online health communities (OHCs) and the impact of persons’ participation in OHCs on their capacity and treatment burden. Patients and Methods A qualitative study of 556 blog posts submitted between January 1, 2007 and December 31, 2017 to 4 diabetes social networking sites was conducted between March 2018 and July 2019. All posts were coded inductively using thematic analysis procedures. Eton’s Burden of Treatment Framework and Boehmer’s Theory of Patient Capacity directed triangulation of themes with existing theory. Results Three themes were identified: (1) cost barriers to care: participants describe individual and systemic cost barriers that inhibit prescribed therapy goals; (2) impact of financial cost on health: participants describe the financial effects of care on their physical and emotional health; and (3) saving strategies to overcome cost impact: participants discuss practical strategies that help them achieve therapy goals. Finally, we also identify that the use of OHCs serves to increase persons’ capacity with the potential to decrease treatment burden, ultimately improving mental and physical health. Conclusion High cost for diabetes care generated barriers that negatively affected physical health and emotional states. Participant-shared experiences in OHCs increased participants’ capacity to manage the burden. Potential solutions include cost-based shared decision-making tools and advocacy for policy change.

RationaleClinical endpoints that constitute successful treatment in severe pneumonia are difficult to ascertain and vulnerable to bias. Utility of a protocolized adjudication procedure to determine meaningful endpoints in severe pneumonia is not well described.ObjectivesTo develop and validate a protocol for classification and adjudication of clinical endpoints in severe bacterial and viral pneumonia in a prospective cohort of critically ill, mechanically ventilated patients.MethodsEach episode of pneumonia was independently reviewed by two of six pulmonary and critical care physician adjudicators. If a discrepancy in at least one critical answer occurred between the two adjudicators, a third adjudicator reviewed the case and answered the specific question(s) for which there was a lack of agreement. If discrepancy remained after all three adjudications, consensus was achieved through committee review.ResultsEvaluation of 784 pneumonia episodes during 593 hospitalizations achieved a 79% crude rate of interobserver agreement defined as agreement between 2 of 3 reviewers. Culture-negative pneumonia was associated with increased interobserver agreement. Multiple episodes of pneumonia and bacterial and viral co-infection in the initial episode of pneumonia were associated with decreased interobserver agreement. For bacterial pneumonia, patients with an adjudicated day 7-8 clinical impression of cure for the initial episode of pneumonia were more likely to be discharged alive compared to patients with a day 7-8 clinical impression of indeterminate (p < 0.01), superinfection (p = 0.03), or a combined impression of persistence and superinfection (p = 0.04). In viral pneumonia, patients with an adjudicated clinical impression of cure for an initial episode of viral pneumonia were more likely to be discharged alive compared to patients with an adjudicated clinical impression of persistence (p < 0.01), indeterminate (p < 0.01), or bacterial superinfection (p < 0.01).ConclusionsWe developed and validated a protocol for classification and adjudication of clinical endpoints in severe pneumonia. This protocol can be applied to cohorts of patients with severe pneumonia to provide uniform assessment of patient-centered endpoints.

BackgroundPatients with severe SARS-CoV-2 pneumonia experience longer durations of critical illness yet similar mortality rates compared to patients with severe pneumonia secondary to other etiologies. As secondary bacterial infection is common in SARS-CoV-2 pneumonia, we hypothesized that unresolving ventilator-associated pneumonia (VAP) drives the apparent disconnect between length-of-stay and mortality rate among these patients.MethodsWe analyzed VAP in a prospective single-center observational study of 585 mechanically ventilated patients with suspected pneumonia, including 190 patients with severe SARS-CoV-2 pneumonia. We developed CarpeDiem, a novel machine learning approach based on the practice of daily ICU team rounds to identify clinical states for each of the 12,495 ICU patient-days in the cohort. We used the CarpeDiem approach to evaluate the effect of VAP and its resolution on clinical trajectories.FindingsPatients underwent a median [IQR] of 4 [2,7] transitions between 14 clinical states during their ICU stays. Clinical states were associated with differential hospital mortality. The long length-of-stay among patients with severe SARS-CoV-2 pneumonia was associated with prolonged stays in clinical states defined by severe respiratory failure and with a lower frequency of transitions between clinical states. In all patients, including those with COVID-19, unresolving VAP episodes were associated with transitions to unfavorable states and hospital mortality.InterpretationCarpeDiem offers a machine learning approach to examine the effect of VAP on clinical outcomes. Our findings suggest an underappreciated contribution of unresolving secondary bacterial pneumonia to outcomes in mechanically ventilated patients with pneumonia, including due to SARS-CoV-2.Abstract FigureGraphical abstractDisentangling the contributions of ICU complications and interventions to ICU outcomes. (A) Traditional approaches evaluate the ICU stay as a black box with severity of illness measured on presentation and dichotomized survival at an arbitrary time point (e.g., day 28) or on ICU or hospital discharge. Hence, the effect of intercurrent complications and interventions cannot be easily measured, a problem that is compounded when ICU stays are long or significantly differ between groups. (B) Defining the ICU course by clinical features during each day in the ICU permits the association of a complication or intervention with transitions toward clinical states associated with favorable or unfavorable outcomes.

Background: The coronavirus disease 2019 (COVID-19) pandemic raised concern for exposure to healthcare providers through aerosol generating procedures, such as bronchoalveolar lavage (BAL). Current society guidelines recommended limiting use of BAL to reduce operators' risk for infection, yet data on the infection rate for providers after BAL is sparse. Since March 2020, our institution used a modified protocol to perform over 450 BALs on intubated COVID-19 patients. We therefore sought to describe the subsequent infectious risks to providers associated with BAL. Methods: Fifty-two pulmonary and critical care providers (faculty and fellows) at our tertiary-care, urban medical center were surveyed. Survey participants were asked to provide the number of BALs on COVID-19 patients they performed, the number of weeks they cared for intensive care unit (ICU) patients with COVID-19, and the results of any SARS-CoV-2 testing that they received. Participants were asked to assess the difficulty of BAL on intubated COVID-19 patients as compared to routine ICU BAL using a numeric perceived difficulty score ranging from 1 (easier) to 10 (harder). Results: We received forty-seven responses from fifty-two surveyed (90% response rate), with 2 declining to participate. Many respondents (19/45, 42%) spent >5 weeks on an ICU service with COVID-19 patients. The number of BALs performed by providers ranged from 0 to >60. Sixteen of the 35 providers (46%) who performed BALs underwent at least one nasopharyngeal (NP) swab to test for SARS-CoV-2, but none were positive. Twenty-seven of the 35 providers (77%) who performed BALs underwent SARS-CoV-2 serology testing, and only one (3.7%) was positive. Respondents indicated occasionally not being able to follow aerosol-minimizing steps but overall felt BALs in COVID-19 patients was only slightly more difficult than routine ICU BAL. Discussion: At a high-volume center having performed >450 BALs on intubated COVID-19 patients with aerosol-limiting precautions, our survey of bronchoscopists found no positive NP SARS-CoV-2 tests and only one positive antibody test result. While the optimal role for COVID-19 BAL remains to be determined, these data suggest that BAL can be safely performed in intubated COVID-19 patients if experienced providers take precautions to limit aerosol generation and wear personal protective equipment.

Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS).To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio2) in moderate to severe ARDS.Phase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao2:Fio2 ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018.Participants were randomized to PES-guided PEEP (n = 102) or empirical high PEEP-Fio2 (n = 98). All participants received low tidal volumes.The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy.Two hundred patients were enrolled (mean [SD] age, 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio2 died (risk difference, 1.7% [95% CI, -11.1% to 14.6%]; P = .88). Days free from mechanical ventilation among survivors was not significantly different (median [interquartile range]: 22 [15-24] vs 21 [16.5-24] days; median difference, 0 [95% CI, -1 to 2] days; P = .85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs 12/98 [12.2%]; risk difference, -8.3% [95% CI, -15.8% to -0.8%]; P = .04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with PES-guided PEEP and 5 patients with empirical PEEP-Fio2.Among patients with moderate to severe ARDS, PES-guided PEEP, compared with empirical high PEEP-Fio2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS.ClinicalTrials.gov Identifier NCT01681225.

Since humanity entered the 20th century, diversity has become a key feature that manifests itself in all aspects of society. As a venue for people and ideas to meet, universities face ever-increasing challenges in fulfilling their cultural mission. With unprecedented human connectivity, cultural competence is more than a goal. It has become an essential skill for students and a key concern for policymakers and practitioners across the world. Considering the strengths and weaknesses of current approaches to cultural competence education, this article aims to elucidate the significance of the notion of cultural self-awareness proposed by Fei Xiaotong, China’s premier social anthropologist. It explores how Fei’s insights can facilitate universities to rethink their conception and delivery of cultural competence education. By challenging the tendency for cultural competence education to be segregated among a range of disciplines and moving it to the core of the university’s curricular offerings, the article promises an approach whereby all students, regardless of their disciplinary backgrounds, can benefit from the full development of their cultural capability, as can the institution, wider community, and society as a whole.

OBJECTIVES Spinal cord stimulation (SCS) therapies are used in the management of patients with complex regional pain syndrome I (CRPS I) and failed back surgery syndrome (FBSS). The purpose of this study was to investigate the racial and health insurance inequalities with SCS therapy in patients with chronic pain who had CRPS I and FBSS. METHODS Patients with chronic pain who had a discharge diagnosis of FBSS and CRPS I were identified using the National Inpatient Sample database. Our primary outcome was defined as the history of SCS utilization by race/ethnicity, income quartile, and insurance status. Multivariable logistic regression was used to determine the variables associated with utilization of SCS therapy. RESULTS Between 2011 and 2015, 40,858 patients who were hospitalized with a primary diagnosis of FBSS and/or CRPS I were identified. Of these patients, 1,082 (2.7%) had a history of SCS therapy. Multivariable regression analysis revealed that compared to White patients, Black and Hispanic patients had higher odds of having SCS therapy (Black patients: odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.12 to 1.77; P = 0.003; Hispanic patients: OR = 1.41; 95% CI, 1.10 to 1.81; P = 0.007). Patients with private insurance had significantly higher odds of having SCS therapy compared with those with Medicare (OR = 1.24; 95% CI, 1.08 to 1.43; P = 0.003). Compared to patients with Medicare, Medicaid patients had lower odds of having SCS therapy (OR = 0.50; 95% CI, 0.36 to 0.70; P

Background Veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) support is increasingly used in the management of COVID‐19‐related acute respiratory distress syndrome (ARDS). However, the clinical decision‐making to initiate V‐V ECMO for severe COVID‐19 still remains unclear. In order to determine the optimal timing and patient selection, we investigated the outcomes of both COVID‐19 and non‐COVID‐19 patients undergoing V‐V ECMO support. Methods Overall, 138 patients were included in this study. Patients were stratified into two cohorts: those with COVID‐19 and non‐COVID‐19 ARDS. Results The survival in patients with COVID‐19 was statistically similar to non‐COVID‐19 patients (p = .16). However, the COVID‐19 group demonstrated higher rates of bleeding (p = .03) and thrombotic complications (p, The survival in patients with COVID‐19 was statistically similar compared to non‐COVID‐19 patients, but the mortality of COVID‐19 patients who had been on a ventilator for longer than 7 days prior to the initiation of ECMO approached 100%.

Animation in medical education has boomed over the past two decades, and demand for distance learning technologies will likely continue in the context of the COVID-19 pandemic. However, experimental data guiding best practices for animation in medical education are scarce.To compare the efficacy of two animated video styles in a diabetes pharmacotherapy curriculum for internal medicine residents.Learners were randomized to receive one of two versions of the same multimodal didactic curriculum. They received identical lectures, group activities, and quizzes, but were randomized to either digital chalk talk (DCT) videos or Sugar-Coated Science (SCS). SCS is an animated series using anthropomorphic characters, stories, and mnemonics to communicate knowledge.Ninety-two internal medicine residents at a single academic medical center received the curriculum within ambulatory medicine didactics.Knowledge was measured at multiple time points, as was residents' self-reported comfort using each medication class covered. Surveys assessed video acceptability and telepresence. Key themes were identified from open-ended feedback.Baseline knowledge was low, consistent with prior needs assessments. On immediate posttest, mean scores were higher with SCS than DCT (74.8% versus 68.4%), but the difference was not statistically significant, p = 0.10. Subgroup analyses revealed increased knowledge in the SCS group for specific medication classes. Delayed posttest showed significant knowledge gains averaging 17.6% across all participants (p0.05); these gains were similar between animation types. SCS achieved significantly higher telepresence, entertainment, and acceptability scores than DCT. Qualitative data suggested that residents prioritize well-designed, multimodal curricula over specific animation characteristics.SCS and DCTs both led to learning within a multimodal curriculum, but SCS significantly enhanced learner experience. Animation techniques exemplified by both SCS and DCTs have roles in the medical educator toolkit. Selection between them should incorporate context, learner factors, and production resources.

Rationale: D-dimer is primarily used in the diagnosis of venous thromboembolic (VTE) disease. Recently the Ddimer test has been used as a marker of inflammation in COVID-19 pneumonia and has been shown to correlate with worse outcomes. An understanding of trajectories and relation to clot burden and outcomes of this novel use of serial measurements of D-dimer in COVID-19 ICU patients remains to be explored. Methods: We reviewed patients who were admitted to the Northwestern Hospital COVID ICUs from 3/1/20 to 7/31/20. We obtained demographics, d-dimer lab values, venous duplex studies from upper and lower extremities (UE/LE dopplers), CT-angiogram (CTA) reports, and mortality outcomes from our electronic medical record database. Reports were processed using string analysis with manual physician validation. Analysis was done in R with nonparametric numeric variables being compared by two-tailed Mann Whitney tests. Results: We had 370 patients in our cohort, with median (interquartile range (IQR)) age being 60 (49-69), 229/370 (62%) male, 128 (35%) of Hispanic ethnicity, 117 (32%) of African-American ethnicity, and 135 (36%) of Caucasian descent. 70 patients died (19%). The total number of VTE imaging tests included: 87 CTAs, 102 UE dopplers, and 232 LE dopplers. Clot was discovered in 43/102 (42%) UE dopplers, 62/232 (27%) of LE dopplers, and 25/87 (29%) of CTAs. Patients underwent a median of 2 (1-3) imaging studies, and 10 (4-20) d-dimer measurements. 79 unique patients (21%) had VTE detected. There was no statistically significant difference in age between the clot vs noclot groups: 57(45-68) vs 61(49-59) years, p=0.34, or BMI: 30.5(25.6-34.8) in clot vs 29(25.4-34.5) kg/m2 in no-clot group (p=0.55). Mortality was significantly higher at 36% in the clot group vs 15% in the group without clot (p

Objectives:. Determine the variation in outcomes and respiratory mechanics between the subjects who are intubated earlier versus later in their coronavirus disease 2019 course. Design:. Retrospective cohort study. Setting:. Northwestern Memorial Hospital ICUs. Patients:. All patients intubated for coronavirus disease 2019 between March 2020 and June 2020. Interventions:. Patients were stratified by time to intubation: 30 subjects were intubated 4–24 hours after presentation and 24 subjects were intubated 5–10 days after presentation. Baseline characteristics, hospitalization, ventilator mechanics, and outcomes were extracted and analyzed. Ten clinically available CT scans were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis. Measurements and Main Results:. Median time from symptom onset to intubation was significantly different between the early and late intubation cohorts, with the latter being intubated later in the course of their illness (7.9 vs 11.8 d; p = 0.04). The early intubation cohort had a lower mortality rate than the late intubation cohort (6% vs 30%, p < 0.001) without significantly different respiratory mechanics at the time of intubation. The late intubation cohort was noted to have higher dead space ratio (0.40 vs 0.52; p = 0.03). On review of CT scans, the late intubation cohort also had more dilated peripheral segments on imaging (two segments vs five segments). Conclusions:. The question as to whether delaying intubation is beneficial or harmful for patients with coronavirus disease 2019-induced hypoxemic respiratory failure has yet to be answered. As our approaches to coronavirus disease 2019 continue to evolve, the decision of timing of intubation remains paramount. Although noninvasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis with delayed intubation.

Rationale: The frequency of superinfection with Aspergillus among patients with severe COVID-19-related respiratory failure is unknown. The association of bronchoalveolar lavage (BAL) fluid markers, such as galactomannan, with the presence of Aspergillus infections is also unclear. Methods: Our cohort included all patients with COVID-19 admitted to the Northwestern Memorial Hospital ICU from March to November 2020 who were intubated and underwent a BAL;patients were identified as having COVID-19 by the presence of a flag in the electronic medical record. We evaluated BAL fluid data for fungal organisms and markers. Data analysis was performed in Excel and Prism, with non-parametric values compared by two-tailed Mann Whitney tests. Results: We identified 274 patients meeting study entry criteria. The median (interquartile range) age was 62 years (47-69), and 93 (34%) were female. 714 BALs were performed on these patients, and 457 galactomannan tests were sent from these BALs. Only six (2.2%) patients grew Aspergillus on BAL fluid culture;one patient never grew Aspergillus but given his significantly elevated BAL galactomannan of 7.81, was empirically treated. The median (IQR) optical density index of galactomannan for the BAL samples that grew Aspergillus was 6.69 (3.37-8.87) compared with 0.08 (0.06-0.13) for those that did not, p 0.5 as positive, with patients who grew Aspergillus on culture as gold standard, the test sensitivity was 91.7% and specificity was 94.6%;using the ATS recommended cutoff of >1.0 as positive, the sensitivity was 75.0% and specificity was 97.5%. The median (IQR) age of patients who grew Aspergillus was 71.5 years (64-80.5) (p=0.02 compared with the overall cohort). Only two were immunocompromised (diffuse large B-cell lymphoma and another was status post liver transplant). Of note, two patients who grew Aspergillus had visible mold or plaque seen during bronchoscopy;three had cavitary findings on imaging;three died. Conclusions: Aspergillus superinfection is uncommon among ventilated patients with COVID-19 but can occur in patients without typical immunocompromising risk factors. BAL fluid galactomannan levels are lower in patients without Aspergillus, and had reasonable specificity especially if cutoff of >1.0 was used. Future analysis should focus on additional factors that differentiate between these two groups.

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatricversusadult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data1as a highly granular reference for the study of immune responses in airways and blood in children.

BackgroundSARS-CoV-2 can cause severe respiratory failure leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2 at our tertiary-care, urban teaching hospital.MethodsWe reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and ICU and hospital lengths-of-stay (LOS) in SARS-CoV-2 patients who received tracheostomies. Early tracheostomy was considered ResultsFrom March 2020 to January 2021, our center had 370 patients intubated for SARS-CoV-2, and 59 (16%) had percutaneous bedside tracheostomy. Median time from intubation to tracheostomy was 19 (IQR 17 – 24) days. Demographics and comorbidities were similar between early and late tracheostomy, but early tracheostomy was associated with shorter ICU LOS and a trend towards shorter ventilation. To date, 34 (58%) of patients have been decannulated, 17 (29%) before hospital discharge; median time to decannulation was 24 (IQR 19-38) days. Decannulated patients were younger (56 vs 69 years), and in regression analysis, pneumothorax was associated was associated with lower decannulation rates (OR 0.05, 95CI 0.01 – 0.37). No providers developed symptoms or tested positive for SARS-CoV-2.ConclusionsTracheostomy is a safe and reasonable procedure for patients with prolonged SARS-CoV-2 respiratory failure. We feel that tracheostomy enhances care for SARS-CoV-2 since early tracheostomy appears associated with shorter duration of critical care, and decannulation rates appear high for survivors.

BackgroundSevere community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations.MethodsWe obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia (VAP) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care.ResultsThe 179 ventilated patients with severe SARS-CoV-2 pneumonia discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days.ConclusionsWith use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP in ventilated patients with SARS-CoV-2 pneumonia are higher than historically reported.

Objectives:. The main objective of this study was to evaluate trends in set tidal volumes across all adult ICUs at a large academic medical center over 6 years, with a focus on adherence to lung-protective ventilation (≤ 8-cc/kg ideal body weight). A secondary objective was to survey providers on their perceptions of lung-protective ventilation and barriers to its implementation. Design:. Retrospective observational analysis (primary objective) and cross-sectional survey study (secondary objective), both at a single center. Participants:. Mechanically ventilated adult patients with a set tidal volume (primary objective) and providers rotating through the Medical and Neurosciences ICUs (secondary objective). Interventions:. None. Measurements and Main results:. From 2013 to 2018, the average initial set tidal volume (cc/kg ideal body weight) decreased from 8.99 ± 2.19 to 7.45±1.34 (p < 0.001). The cardiothoracic ICU had the largest change in tidal volume from 11.09 ± 1.96 in 2013 to 7.97 ± 1.03 in 2018 (p < 0.001). Although the majority of tidal volumes across all ICUs were between 6.58 and 8.01 (interquartile range) in 2018, 27% of patients were still being ventilated at volumes greater than 8-cc/kg ideal body weight. Most surveyed respondents felt there was benefit to lung-protective ventilation, though many did not routinely calculate the set tidal volume in cc/kg ideal body weight, and most did not feel it was easily calculable with the current electronic medical record system. Conclusions:. Despite a trend toward lower tidal volumes over the years, in 2018, over a quarter of mechanically ventilated adult patients were being ventilated with tidal volumes greater than 8 cc/kg. Survey data indicate that despite respondents acknowledging the benefits of lung-protective ventilation, there are barriers to its optimal implementation. Future modifications of the electronic medical record, including a calculator to set tidal volume in cc/kg and the use of default set tidal volumes, may help facilitate the delivery of and adherence to lung-protective ventilation.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic raised concern for exposure to healthcare providers through aerosol generating procedures, such as bronchoalveolar lavage (BAL). Current society guidelines recommended limiting use of BAL to reduce operators’ risk for infection, yet data on the infection rate for providers after BAL is sparse. Since March 2020, our institution used a modified protocol to perform over 450 BALs on intubated COVID-19 patients. We therefore sought to describe the subsequent infectious risks to providers associated with BAL.MethodsFifty-two pulmonary and critical care providers (faculty and fellows) at our tertiary-care, urban medical center were surveyed. Survey participants were asked to provide the number of BALs on COVID-19 patients they performed, the number of weeks they cared for intensive care unit (ICU) patients with COVID-19, and the results of any SARS-CoV-2 testing that they received. Participants were asked to assess the difficulty of BAL on intubated COVID-19 patients as compared to routine ICU BAL using a numeric perceived difficulty score ranging from 1 (easier) to 10 (harder).ResultsWe received forty-seven responses from fifty-two surveyed (90% response rate), with 2 declining to participate. Many respondents (19/45, 42%) spent >5 weeks on an ICU service with COVID-19 patients. The number of BALs performed by providers ranged from 0 to >60. Sixteen of the 35 providers (46%) who performed BALs underwent at least one nasopharyngeal (NP) swab to test for SARS-CoV-2, but none were positive. Twenty-seven of the 35 providers (77%) who performed BALs underwent SARS- CoV-2 serology testing, and only one (3.7%) was positive. Respondents indicated occasionally not being able to follow aerosol-minimizing steps but overall felt BALs in COVID-19 patients was only slightly more difficult than routine bronchoscopy.DiscussionAt a high-volume center having performed >450 BALs on intubated COVID-19 patients with aerosol-limiting precautions, our survey of bronchoscopists found no positive NP SARS-CoV-2 tests and only one positive antibody test result. While the optimal role for COVID-19 BAL remains to be determined, these data suggest that BAL can be safely performed in intubated COVID-19 patients if experienced providers take precautions to limit aerosol generation and wear personal protective equipment.

Animation is increasingly incorporated into multimedia teaching tools in medical education. Despite enthusiasm about animation among learners and educators, evidence is limited and conflicting regarding the effectiveness of animation in medical education. In this how-to guide and pilot study, a team of clinician-educators have cataloged their efforts to learn the art of animation and understand how to most effectively integrate animation into a flipped classroom curriculum. In this pilot, internal medicine residents responded that an animated video series using anthropomorphic characters and metaphorical dialogue and narrative was an accessible, acceptable, and effective method of teaching the antihyperglycemic medications for type 2 diabetes mellitus. This study paves a path for further exploration of the intersection between multimedia, entertainment, and cognitive theory in graduate medical education. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40670-020-00959-4) contains supplementary material, which is available to authorized users.

Phenomenon: Although most premedical students shadow physicians prior to starting medical school, there is no set of guidelines or expectations to facilitate effective experiences for students and physicians, nor is there data on the value of shadowing medical trainees as a way to learn about the training environment. We sought to understand premedical student perspectives on an intensive resident shadowing experience.This was a qualitative study using anonymous data from focus groups conducted with premedical student participants in a month-long time motion analysis of internal medicine interns at two large academic medical centers. The authors convened, professionally transcribed verbatim, and analyzed data using step-by-step thematic analysis from 3 focus groups in 2012. Focus group questions included goals of participants, shadowing experiences, patient safety experiences, and thoughts on physician training.Twenty of the 22 students who were involved in the time motion study participated in the focus groups (91%). Three major themes were generated from the transcripts: qualities of a good physician, the inefficiencies of the healthcare system and the hospital, and the realities of graduate medical education. Insights: The intensive shadowing experience exposed premedical students to the hospital environment and many of the challenges they will face as future residents. Observing patient care firsthand, students considered the qualities of good intern physicians and appreciated the teamwork and collaboration essential to patient care in an academic medical center. Students witnessed some of the fundamental challenges of graduate medical training, including time pressures, documentation requirements, and the medical hierarchy. They also observed the difficulties of providing quality care in the current healthcare system, including hospital inefficiencies, interprofessional tensions, and financial barriers to care. Intensive shadowing of residents can begin the process of socialization to the culture of medicine by giving premedical students a realistic perspective of both positive and negative aspects of medical training and inpatient care.

Circadian rhythms are an integral part of life on earth. Circadian rhythms play a fundamental role in homeostasis as they ensure coordination between the environment and an organism's behavior and physiology. This coordination is called entrainment. Entrainment depends on environmental cues known as zeitgebers. Human zeitgebers include light (primary zeitgeber), sleep, eating, exercise, and activity. Circadian rhythms are disrupted in critically-ill patients due to both critical illness and current intensive care unit (ICU) practices. Disruptions in circadian rhythms are tightly linked with ICU sleep disruption. Together these entities potentiate numerous adverse outcomes including delirium, metabolic derangements, cardiovascular instability, and immune compromise. Herein, we will highlight potential areas for care improvement via chronobundles. We suggest bright light during the day, maintaining darkness, and protecting sleep at night, intermittent rather than continuous feeds, and activity via mobilization during the day. Optimizing circadian rhythms is a low-risk intervention that is underutilized in current ICU practice. This optimization could be a powerful tool in helping to improve outcomes in the critically-ill patient.

Background A positive urine culture often drives initiation of antimicrobials even in the absence of symptoms. Our objectives were to evaluate the knowledge and practice patterns related to ordering urine cultures in patients with indwelling urinary catheters. Methods We performed chart reviews of catheter-associated urinary tract infections (CAUTIs) at our academic health care system between October 1, 2015, and September 30, 2017, to assess practice patterns related to the assessment of potential CAUTIs. Following this, we surveyed physicians and nurses about indications for ordering urine cultures in catheterized patients between January 11, 2018, and April 17, 2018. The accuracy of these indications was assessed based on Infectious Diseases Society of America CAUTI and asymptomatic bacteriuria guidelines. Results On chart review, we identified 184 CAUTIs in 2 years. In 159 episodes (86%), urine cultures were ordered inappropriately. In 114 episodes (62%), CAUTI criteria were met by “pan-culturing” rather than symptom-directed testing. Twenty cases (11%) experienced partial or delayed management of other infections, drug adverse events, and Clostridioides difficile infections (CDIs). On our survey, we received 405 responses, for a response rate of 45.3%. Mean scores varied by occupation and level of training. Nurses were more likely than physicians to consider change in appearance (61% vs 23%; P < .05) and odor (74% vs 42%; P < .05) of urine as indications to order urine cultures. Conclusions Our data reveal specific knowledge gaps among physicians and nurses related to ordering urine cultures in catheterized patients. The practice of pan-culturing and inappropriate urine culture orders may contribute to overdiagnosis of surveillance CAUTIs, delay in diagnosis of alternative infections, and excess CDIs., Our assessment of knowledge and practices related to urine cultures in catheterized patients revealed specific gaps based on occupation and level of training. These data can be used to develop decision support tools and tailored diagnostic stewardship educational interventions.

Background Immune checkpoint inhibitors have improved clinical outcomes including survival in several malignancies but have also been associated with a range of immune-related adverse events (irAEs). Neurological irAEs are rare compared to the more typical skin, gastrointestinal, and endocrine toxicities, and are often underrecognized and challenging to diagnose. Here, we report a case of seronegative autoimmune autonomic ganglionopathy (AAG) induced by dual immune checkpoint inhibitor therapy (ICI) in a patient with metastatic melanoma. Case presentation A patient with metastatic melanoma was treated with ipilimumab and nivolumab. He developed a constellation of new symptoms including nausea, fatigue, and severe orthostatic hypotension refractory to fluid resuscitation. An infectious, cardiac, neurologic, and endocrine workup were unrevealing. Cardiovascular autonomic testing revealed poor sympathetic nervous system responses. He was diagnosed with seronegative AAG and significantly improved with immunomodulatory therapies including IVIG and steroids as well as varying doses of midodrine and fludrocortisone. He was able to restart nivolumab without recurrence of his symptoms. However, the AAG reoccurred when he was re-challenged with ipilimumab and nivolumab due to disease progression. While the AAG was manageable with steroids at that time, unfortunately his melanoma became resistant to ICI. Conclusions Immune checkpoint inhibitors can have a wide range of unusual, rare irAEs, including neurotoxicity such as AAG. Clinicians should maintain suspicion for this toxicity so that treatment can be rapidly provided to avoid disability.

By contextualizing university internationalization within other forces that are shaping the higher education landscape, such as globalization, regionalization, and New Public Management, this chapter provides a critical analysis of internationalization’s definitions, ideologies, motives, and institutional strategies that emphasize the complexities, controversies, and gaps in conceptualizing university internationalization. Although internationalization has become one of the topics in higher education discussed most, there is no well-established conceptual framework of the phenomenon. By using the extensive previous works on this phenomenon, generic components of institutional international strategies were identified that indicated the structural and philosophical similarities between institutions and allowed meaningful comparisons to be made between universities’ internationalization efforts.

This chapter reviews the global context that compels universities to reconsider their missions, goals, and responsibilities and highlights the internationalization strategies higher education institutions around the world have adopted in response to the changing global landscape. As universities invest substantial resources to internationalize their teaching, research, and services, better measurements of their performance are needed urgently to provide evidence for policymaking and increase university operation’s accountability and transparency. By reviewing the existing tools used to monitor and assess university internationalization briefly, Yuan identifies these instruments’ shortcomings and presents the research questions and methodologies used to develop a new set of measures of universities’ internationalization performance.

The final chapter concludes the project and examines university internationalization’s future. Yuan argues that if university internationalization indeed has a future, it must shift its focus from structural to cultural diversity to fulfill higher education institutions’ cultural mission. In addition, Yuan points out the uncertainties that cloud the future of university internationalization and common challenges in achieving meaningful internationalization that face universities in all countries, such as international students’ learning experiences and outcomes, the conflicts between an international profile and national identity, and internationalization’s influences on social equity. The chapter concludes with a reflection on better performance measures for universities, which highlights that the fundamental difficulty in measuring a complex phenomenon rests in capturing the outcomes rather than the activities’ input and output.

Drawing on the nation-based analysis of China, Singapore, and Australia, this chapter establishes a shared conceptual framework of university internationalization and outlines the critical generic dimensions and components of the phenomenon across individual cases. The framework established proves that university internationalization is not an intangible concept, but one that can be constructed. Constructing the phenomenon also is of great importance in developing measurements of university internationalization performance, and this framework served as the basis for selecting the indicators to do so. On the other hand, as internationalization is interpreted variously in different national and institutional contexts, it highlights the phenomenon’s dynamic nature. Because internationalization is a process, new elements may emerge in the future that need to be integrated into the conceptual framework.

Developing measurements for university internationalization is a challenging task. Fortunately, predecessors’ endeavors simplified this task significantly. This chapter provides a detailed analysis of the existing tools used to assess university internationalization performance, and shows these tools’ similarities and differences in the focused national context, their purpose, unit of measurement, and methods of data collection. Further, Yuan identifies the common dimensions and components of university internationalization the existing instruments capture and summarizes all indicators available currently. By doing so, the existing indicators’ advantages and shortcomings as preferred performance measurements are presented vividly. This chapter lays the foundation for developing the new indicator set in this project.