Bayesian methods: a potential path forward for sepsis trials.

BACKGROUND: Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods. METHODS: We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60-0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment. RESULTS: In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored. CONCLUSIONS: Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.

The Association of "GOOP" on Gross Examination of Fine Needle Aspiration Samples and On-Site Adequacy.

BACKGROUND: Rapid on-site cytologic evaluation (ROSE) is not always available for fine needle aspiration (FNA) specimens. We have examined the relationships between the presence of "GOOP" (defined as gooey white material) on FNA aspirates, on-site adequacy (OSA), and diagnosis. METHODS: Consecutive FNA samples obtained over the study interval were included. Samples were assessed macroscopically for the presence or absence of GOOP (GOOP+ or GOOP-). GOOP+ samples were further characterized as shiny (G+S) or cheesy (G+C). Gross descriptors were correlated with OSA and final diagnoses. RESULTS: Of the 204 sites biopsied, 102 were malignant, 94 benign, and 8 nondiagnostic. The presence of GOOP was highly predictive for adequacy (positive predictive value 98%). While these correlations for GOOP positivity were significant, the absence of GOOP did not rule out adequacy or malignancy. The presence of GOOP was also significantly correlated with a malignant diagnosis. CONCLUSIONS: We have prospectively demonstrated that the presence of GOOP correlates strongly with adequacy. This may be of value for those for whom ROSE is not available and, when available, may help prioritize specimens for on-site review.

Rapid On-Site Cytologic Evaluation: A Feasibility Study Using Ancillary Interventional Pulmonary Personnel.

BACKGROUND: Ancillary health professionals helping in a procedural service is a common practice everywhere. OBJECTIVES: This was a proof-of-concept study to assess feasibility of using ancillary personnel for rapid on-site cytologic evaluation (ROSE) at interventional pulmonary procedures. METHODS: After a training interval, a respiratory therapist (RT) performed ROSE on consecutive interventional pulmonary specimens. Sample sites included lymph nodes, lung, liver, and the left adrenal gland. RT findings were subsequently correlated with blinded cytopathology-performed ROSE and with final histopathology results, with primary foci of adequacy and the presence or absence of malignancy. RESULTS: Seventy consecutive cases involved 163 separate sites for ROSE analysis. Adequacy: There was a high level of concordance between RT-performed ROSE (RT-ROSE) and cytopathology ROSE (CYTO-ROSE). They agreed upon the adequacy of 159 specimens. The Cohen's κ coefficient ± asymptotic standard error (ASE) was 0.74 ± 0.175, with p < 0.0001. Malignancy: RT-ROSE concurred highly with CYTO-ROSE, with agreement on 150 (92%) of the 163 specimens. Cohen's κ coefficient ± ASE was 0.83 ± 0.045, with p < 0.0001. When the comparison was for malignancy by case rather than individual site, Cohen's κ coefficient ± ASE was 0.68 ± 0.08, with p < 0.0001. CONCLUSION: This study demonstrates that ancillary personnel supporting an interventional pulmonary service can be trained to perform initial ROSE. Cytopathology can be called after sampling and staining have produced adequate samples. This setup streamlines ROSE evaluation with regard to time and cost.

The Performance of Diagnostic Criteria for Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.

OBJECTIVE: The diagnostic criteria for secondary hemophagocytic lymphohistiocytosis (HLH) have not been validated in the critically ill adult population. We set out to evaluate the performance of diagnostic criteria and determine the ferritin cutoff in critically ill adults. DESIGN: A retrospective single-center study. SETTING AND PATIENTS: Patients admitted to intensive care unit between 2008 and March 2010. Data were collected on consecutive patients who had ferritin measured. Charts were reviewed for the diagnostic criteria of HLH and components of Hscore. MEASUREMENTS AND MAIN RESULTS: A total of 445 patients had a ferritin level measured during the study period. A diagnosis of HLH was made for 10 patients. Having 5 of 6 criteria had a specificity of 97% and a sensitivity of 70%. Hemophagocytosis was found in 41 (47.1%) of 87 bone marrow biopsies. Two hundred thirty-one patients had a ferritin level above 500 ng/dL. When determining the odds of HLH being clinically diagnosed, the optimal cut point for ferritin was 1197 ng/dL. When determining the odds of HLH based on the Hscore, the best cutoff was 143.5 (sensitivity of 90% and specificity of 90%) and patients who had HLH in our study population had an Hscore of 203.8 ± 64.9. CONCLUSION: In this cohort of critically ill patients, the HLH criteria are specific for HLH but not sensitive. Critically ill patients can have a higher incidence of hemophagocytosis without HLH. A higher ferritin cutoff in combination with 5 other clinical criteria is comparable to the Hscore for the recognition of HLH in the critically ill population.

Using a Facebook group to facilitate faculty-student interactions during preclinical medical education: a retrospective survey analysis.

BACKGROUND: Strong learner-teacher relationships are associated with more successful learning outcomes. With shortened modular curricula and increased availability of online resources, fostering faculty interaction with preclinical medical students has become more challenging. We sought to enhance learner-teacher relationships by engaging in discussion with preclinical medical students in their own online space. METHODS: We utilized a closed Facebook discussion group, where faculty and students voluntarily joined in informal discussions and shared announcements related to their courses. The closed discussion group allowed only participating students and faculty to see others' posts within the group. This provided a platform to freely interact within the confines of the group while maintaining privacy for the personal Facebook accounts of both faculty and students. We utilized the discussion group through three separate organ system-based modules for 14 weeks. Afterward, students were asked to complete an anonymous, voluntary online survey about their experience. RESULTS: 94.1% (160/170) of enrolled second-year medical students joined the voluntary FB discussion group. There were 214 posts, 628 comments, and 4166 reactions in this discussion group during the three modules. Of the students in the group, 74.4% (119/160) responded to the online survey. Overall, students strongly agreed that the Facebook discussion group fostered better rapport with faculty, helped content learning, and improved emotional well-being. Also, they felt more comfortable seeking academic help after using the discussion group. They reported a slight preference for Facebook over email as a medium for asking questions, but no preference for either as a medium for distributing announcements. Students overwhelmingly recommended that the discussion group should be continued in future years. CONCLUSION: The Facebook discussion group was a free, efficient, and effective method of cultivating the learner-teacher relationship with the preclinical medical students, resulting in reported enhancement of learning and morale.

Efficacy and Safety of the Early Addition of Vasopressin to Norepinephrine in Septic Shock.

BACKGROUND: Delays in achievement of target mean arterial pressure (MAP) have been associated with increased mortality in patients with septic shock. Vasopressin may be added to norepinephrine to raise MAP or decrease norepinephrine dosage. The purpose of this study was to determine whether early initiation of vasopressin to norepinephrine resulted in a reduced time to target MAP compared to norepinephrine monotherapy. METHODS: This retrospective cohort study compared early addition of vasopressin within 4 hours of septic shock onset to norepinephrine versus initial norepinephrine monotherapy in medically, critically ill patients with septic shock admitted from May 2014 to October 2015. Time to goal MAP was compared using Student t test and examined with Kaplan-Meier curves. Changes in Sequential Organ Failure Assessment (SOFA) scores were evaluated with Wilcoxon rank sum test. RESULTS: Each group contained 48 patients. Mean arterial pressure (61.5 vs 58.6 mm Hg) and intravenous fluid volume received at vasopressor initiation (14.3 vs 25.2 hours, P = .014) were similar. Patients started on early vasopressin achieved and maintained goal MAP sooner (6.2 vs 9.9 hours, P = .023), experienced greater reductions in SOFA scores at 72 hours (-4 vs -1, P = .012), and had shorter hospital durations (343 vs 604 hours, P = .014). Not initiating early vasopressin trended toward an association with increased time to goal MAP (P = .067). CONCLUSION: Early initiation of vasopressin in patients with septic shock may achieve and maintain goal MAP sooner and resolve organ dysfunction at 72 hours more effectively than later or no initiation.

Effect of Etomidate on Pneumonia Development in Critically Ill, Nontrauma Patients.

PURPOSE:: To determine whether etomidate use before intubation increased development of hospital-acquired pneumonia (HAP) in critically ill, nontrauma patients. MATERIALS AND METHODS:: A single-center, retrospective, cohort study of critically ill, nontrauma patients admitted to the medical intensive care unit (ICU) from 2012 to 2015 and intubated with or without etomidate was conducted. Demographics, comorbidities, primary diagnosis, critical illness scores, concomitant medications, and outcomes were obtained from medical records. Student t, chi-square, and Fisher exact tests were performed as appropriate. Relevant characteristics were modeled using logistic regression techniques to determine whether any predicted HAP independently. RESULTS:: Of the 174 patients, 94 (54%) received etomidate and 80 (46%) did not. There was no difference in HAP between etomidate and no etomidate groups (13.8% vs 23.7%, P = .092). Duration of mechanical ventilation (4.4 vs 4.6 days, P = .845), ICU length of stay (7.4 vs 6.9 days, P = .547), ICU mortality (14.9% vs 12.5%, P = .648), and hospital mortality (17% vs 16.2%, P = .892) were similar between the groups. For each 1-day increase in mechanical ventilation duration, the likelihood of HAP development increased by 21%. Patients who received etomidate but no neuromuscular-blocking drug were 80% less likely to develop HAP than those who did not receive etomidate or a neuromuscular-blocking drug (odds ratio: 0.202, 95% confidence interval: 0.045-0.908). CONCLUSION:: Etomidate use was not associated with a difference in HAP development in critically ill, nontrauma patients.

Discontinuation of Vasopressin Before Norepinephrine in the Recovery Phase of Septic Shock.

BACKGROUND: Guidance for the discontinuation of vasopressors in the recovery phase of septic shock is limited. Norepinephrine is more easily titrated; however, septic shock is a vasopressin deficient state, which exogenous vasopressin endeavors to resolve. Discontinuation of vasopressin before norepinephrine may result in clinically significant hypotension. METHODS: This retrospective, cohort study compared discontinuation of norepinephrine and vasopressin in medically, critically ill patients in the recovery phase of septic shock from May 2014 to June 2016. Difference in clinically significant hypotension after norepinephrine or vasopressin discontinuation was evaluated with χ2 test. Linear regression was performed, examining the effect of agent discontinuation on clinically significant hypotension. Baseline variables were examined for a bivariate relationship with clinically significant hypotension; those with P < .2 were included in the model. RESULTS: Vasopressin was discontinued first or last in 62 and 92 patients, respectively. Sequential Organ Failure Assessment scores at 72 hours (7.9 vs 7.6, P = .679) were similar. In unadjusted analysis, when vasopressin was discontinued first, more clinically significant hypotension developed (10.9% vs 67.8%, P < .001). There was no difference in intensive care unit (174 vs 216 hours, P = .178) or hospital duration (470 vs 473 hours, P = .977). In adjusted analyses, discontinuing vasopressin first was associated with increased clinically significant hypotension (odds ratio [OR]: 13.837, 95% confidence interval [CI]: 3.403-56.250, P < .001) but not in-hospital (OR: 0.659, 95% CI: 0.204-2.137, P = .488) or 28-day mortality (OR: 0.215, 95% CI: 0.037-1.246, P = .086). CONCLUSION: Adult patients receiving norepinephrine and vasopressin in the resolving phase of septic shock may be less likely to develop clinically significant hypotension if vasopressin is the final vasopressor discontinued.

Nonpharmacist Health Care Providers' Knowledge of and Opinions Regarding Medication Costs in Critically Ill Patients.

Purpose: Medication cost is frequently overlooked when treating critically ill patients. Stewardship of health care resources in high-utilization settings is imperative. This study was conducted to determine nonpharmacist health care providers' knowledge and perceptions of medication costs in a medical intensive care unit (MICU). Methods: Nonpharmacist health care providers in a MICU completed a 27-item survey. The survey queried perceptions regarding medication cost, cost-limiting strategies, and most/least expensive medications in 8 classes, medication price ranges, and intravenous-to-oral comparisons for commonly prescribed medications. Responses were analyzed using descriptive statistics and compared between providers using Fisher exact tests. Results: Among 98 health care providers (76 medical trainees, 5 attending physicians, 17 nurses), when ordering a medication, 49% consider its cost. Few (15%) providers considered themselves knowledgeable regarding medication costs with no difference between providers (P = .174). Attending physicians were more aware of the most/least expensive medications than residents (correct out of 16: 9.6 vs 8.5, P = .044). The correct price ranges for select medications (11%-36%, P = .373) and intravenous-to-oral relative costs (3%-49%, P = .596) were similarly low. Most (59%) believed pharmacists limit expensive medication use, particularly senior physicians (58% resident vs 100% attending, P = .007). Conclusion: In spite of a goal of cost consideration, most nonpharmacist health care providers are unaware of medication costs and fail to include them in decision making. These knowledge gaps and perceptions should inform future efforts to improve knowledge and attitudes regarding medication costs.

Fatal Case of Disseminated Cryptococcosis In a Young Man.

A young Hispanic man in histhirties presented with a two-week history of headaches, fever, and fatigue. Laboratory data revealed anemia, leucocytosis, thrombocytopenia, and elevation of liver enzymes. He was admitted to the hospital with concerns for a tick-borne illness and started on broad-spectrum antibiotics. Further investigations led to discovery of an immune compromised state due to Human Immunodeficiency Virus (HIV). The patient developed rapidly progressive multi-organ system failure, and succumbed to his illness within 72 hours of admission. A diagnosis of disseminated acute cryptococcal infection involving multiple organs (brain, heart, lungs, liver, spleen, pancreas and kidneys) was made on autopsy. The severity of the infection along with the underlying immunocompromised status contributed to his insidious presentation, rapid progression, and ultimately death.

Impact of Targeted Educational Interventions on Clostridium difficile Infection Treatment in Critically Ill Adults.

Background: Clostridium difficile infection (CDI) is a growing clinical and economic burden throughout the world. Pharmacists often are members of the primary care team in the intensive care unit (ICU) setting; however, the impact of pharmacists educating other health care providers on appropriateness of CDI treatment has not been previously examined. Objective: This study was performed to determine the impact of structured educational interventions on CDI treatment on appropriateness of CDI treatment and clinical outcomes. Methods: This was a single-center, retrospective, cohort study of patients with CDI in the medical ICU at an academic medical center between January and June 2014 (pre-period) and 2015 (post-period). All patients were evaluated for appropriate CDI treatment before and after implementing pharmacist-provided educational interventions on CDI treatment. Results: Patients in the post-period were prescribed appropriate CDI treatment more frequently than patients in the pre-period (91.7% vs 41.7%; p = .03) and received fewer inappropriate doses of a CDI treatment agent (14 doses vs 30 doses). Patients in the pre-period had a shorter ICU length of stay [1.5 days (range, 1-19) vs 3.5 days (range, 2-36); p = .01] and a similar hospital length of stay [9.5 days (range, 4-24) vs 11.5 days (range, 3-56); p = .30]. Total time spent providing interventions was 4 hours. Conclusion: Patients had appropriate CDI treatment initiated more frequently in the post-period. This low-cost intervention strategy should be easy to implement in institutions where pharmacists interact with physicians during clinical rounds and should be evaluated in institutions where interactions between pharmacists and physicians occur more frequently in non-rounding situations.

Acute Eosinophilic Pneumonia: Pyrethroid Exposure & Change In Smoking Habit!

We report a case of Acute Eosinophilic Pneumonia (AEP) in a 29-year-old white woman with recent use of a'flea bomb' (containing pyrethroids) at home while remaining indoors, about 48 hours prior to presentation, and recent change in smoking habit (restarted 2 weeks prior after quitting for 10 years). She presented with two days of worsening fever, shortness of breath, productive cough, developed hypoxemic respiratory failure and ARDS. She required a PEEP of 20 and 100% FiO2 to maintain oxygenation. Bronchoalveolar lavage showed 36% Eosinophils. She was given IV steroids with dramatic clinical and radiological improvement. To the best of our knowledge, this is the second report associating AEP with pyrethroid exposure.

Left adrenal biopsy using the convex curvilinear ultrasound scope.

Effective use of the convex curvilinear ultrasound bronchoscope in the esophagus (EUS-B) is well described. EUS-B has not been described for diagnostic sampling of the left adrenal gland. We describe 6 cases of diagnostic fine-needle aspiration of the left adrenal gland using EUS-B. This capacity increases the diagnostic capabilities of the pulmonologist experienced in EUS-B.

Stress Ulcer Prophylaxis use in the Intensive care Unit before and after House Staff Education.

PURPOSE: We hypothesize that stress ulcer prophylaxis with acid suppressant medications (ASM) is overused and educating house-staff will decrease this. METHODS: Retrospective chart review in two six-month phases. House staff was educated prior to phase II. Rates of SUP were calculated for ICU stay, medicine floor, and at discharge. RESULTS: There were 625 ICU admissions. Analysis was done on 106 and 118 patients in each phase. SUP use decreased from 62% to 37% in patients with no indications (p value < 0.01). CONCLUSION: Education can have a significant impact on the appropriate use of medications. Even after this significant decrease, rates of inappropriate usage could be considered unacceptable.

"The Scalpel or the Needle for Superior Vena Cava syndrome"?

Acute Superior Vena Cava (SVC) syndrome from thrombosis is an increasingly recognized complication of intravascular devices. We present a 31 year old woman with an infusion port placed for chemotherapy who developed acute SVC obstruction. A computerized tomograpy (CT) of chest revealed an occlusive thrombus within the SVC extending into the right atrium. Catheter-guided thrombolysis and surgical thrombectomywere felt to impose prohibitive risks. Worsening symptoms led to the use of systemic thrombolysis with tissue plasminogen activator (t-PA) leading to dramatic improvement in symptoms. A repeat CT revealed a reduction of the right atrial thrombus and SVC occlusion had resolved.

One- versus two-specimen Xpert strategy to discontinue airborne isolation in suspected pulmonary tuberculosis: systematic review and meta-analysis.

BACKGROUND: Evaluation of a patient with suspected pulmonary tuberculosis (TB) involves initiation of airborne infection isolation (AII). However, guidelines detailing discontinuation of AII utilizing the Xpert MTB/RIF provide little clarity between use of one-specimen (1-Xpert') versus two-specimens (2-Xpert'). OBJECTIVES: To evaluate the diagnostic accuracy of one-Xpert versus two-Xpert strategy in guiding discontinuation of AII. METHODS: Data sources: PubMed, Embase, and EBSCO databases. STUDY ELIGIBILITY CRITERIA: Studies providing diagnostic accuracy data for one- versus two-Xperts in discontinuation of AII. PARTICIPANTS: Adult patients with suspected TB. TESTS: Xpert MTB/RIF on one- versus two-sputum specimens. Reference standard: Solid and liquid culture media. Assessment of risk of bias: Quality Assessment of Diagnostic Accuracy Studies tool was used. Methods of data synthesis: Meta-analysis was performed to calculate the pooled sensitivities and specificities using Stata 17.2. RESULTS: Four studies were included involving 1776 patients. A total of 68% were males, 36% were HIV positive, and 80% participants belonged to the United States. In patients with suspected pulmonary TB, 7% (95% CI, 6-9%) participants were found to have culture-positive MTB. For one-Xpert strategy, the pooled sensitivity was 86% (95% CI, 75-92%; I2, 1.05%) and specificity was 100% (95% CI, 99-100%; I2, 36%). Two-Xpert strategy had a pooled sensitivity of 92% (95% CI, 84-96%; I2, 16%) and a specificity of 100% (95% CI, 98-100%; I2, 27%). There was statistically significant difference between sensitivities of one-Xpert and two-Xpert strategies (p 0.05) with no statistically significant difference in their specificities. DISCUSSION: The results of this review must be interpreted in the context of a predominantly low-TB prevalence setting. Two-Xpert strategy has an incrementally higher sensitivity when compared with one-Xpert strategy with similar specificities between the two. Obtaining a second Xpert is crucial for individuals with a continued high suspicion for TB or those at a high risk of morbidity/mortality from TB.

Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology-A Potential Diagnostic Pitfall.

Tumors of the lung with a spindle cell morphology require consideration of many entities in the differential diagnosis, including metastases. Ancillary immunohistochemical stains but also molecular studies are typically required to arrive at the proper diagnosis. We present a case of a 71-year-old woman with multiple lung nodules, mediastinal lymphadenopathy, and a history of uterine cancer who underwent endobronchial ultrasound-guided fine needle aspiration and biopsy of the lung and mediastinal lymph nodes. A sampling of the lung lesion showed a cytologically bland neoplasm with spindle cell morphology, lacking necrosis or brisk mitotic activity. In conjunction with the cytomorphology, strong and diffuse Transducin-like enhancer of split 1 (TLE1) reactivity in the tumor cells initially raised the diagnosis of synovial sarcoma; however, subsequent results of additional testing showed strong and diffuse expression with AE1/AE3, CK 8/18, TTF-1, synaptophysin and chromogranin and focal or negative staining with a large number of other antibodies. This warranted a diagnosis of a carcinoid tumor. This is the first report of TLE1 staining in a carcinoid tumor of the lung. Therefore, when evaluating tumors of the lung with spindle cell morphology in which the differential diagnosis may include both carcinoid tumor and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an expanded immunohistochemical staining panel.

The yield and impact of pulmonologist-performed EUS-B-FNA of subdiaphragmatic lesions-an institutional experience.

INTRODUCTION: Pulmonologists can biopsy structures below the diaphragm using the convex curvilinear ultrasound bronchoscope via the esophagus (EUS-B). The literature with respect to the value of EUS-B, rapid on-site evaluation, and final diagnostic yield for structures below the diaphragm is limited. We review our institutional experience. MATERIALS AND METHODS: Our database was queried retrospectively for EUS-B fine needle aspirations (FNAs) from 2013 to 2021. All procedures involving EUS-B-FNA of subdiaphragmatic structures were selected for analysis. The following data elements were collected for each patient: age, gender, clinical indication, sample site, on-site adequacy (OSA), preliminary and final diagnoses, and sufficiency of cell block for ancillary studies. RESULTS: A total of 75 subdiaphragmatic sites were biopsied in 74 patients. Of which, 87% of samples subjected to rapid on-site evaluation were deemed to contain adequate material (OSA+). There were no false-positive OSAs. Six cases remained nondiagnostic at the final diagnosis. The final diagnostic yield (with cell block) was 92% (69/75 cases). Cell block was sufficient for immunohistochemistry or special stains in all applicable cases (n = 36). Molecular testing was requested for 11 cases and successful in 10 (91%). Sampling of subdiaphragmatic sites changed the stage in 67% (38/57) of lung cancer patients. CONCLUSIONS: Pulmonologists can perform EUS-B-FNA of subdiaphragmatic sites with high OSA and final diagnostic yield when assisted by cytopathologists. Strong correlations exist between OSA, cell block adequacy, and subsequent capacity to perform ancillary testing. EUS-B below the diaphragm can make an important contribution to the diagnosis of lung cancer, nonpulmonary malignancies, and other diseases.