Palliative Care Clinicians' Views on Metrics for Successful Specialist Palliative Care Delivery in the ICU.

CONTEXT: A quarter of palliative care (PC) clinicians' consultations are now requested from the intensive care unit (ICU). Despite this high usage, a standardized set of quality metrics for PC delivery in the ICU does not exist. OBJECTIVES: To explore PC clinicians' views on how to best measure quality of care delivery in their role as a consultant in the ICU setting. METHODS: Secondary analysis of a parent dataset consisting of qualitative data from semi-structured interviews exploring ways to optimize PC clinicians' role in the ICU. Nineteen participants were recruited across five academic medical centers in the US. Participants included PC physicians (n = 14), nurse practitioners (n = 2), and social workers (n = 3). Thematic analysis with an inductive approach was used to generate themes. RESULTS: We identified two central themes: difficulties in measuring PC quality in the ICU (theme 1) and tension between the role of PC and metrics (theme 2). Theme 1 had two subthemes related to logistical challenges in measuring outcomes and PC clinicians' preference for metrics that incorporate subjective feedback from patients, family members, and the primary ICU team. Theme 2 described how PC clinicians often felt a disconnect between the goal of meeting a metric and their goals in delivering high-quality clinical care. CONCLUSION: Our findings provide insight into PC clinician perspectives on quality metrics and identify major barriers that need to be addressed to successfully implement quality measurement in the ICU setting.

Running from a Bear: How We Teach Vasopressors, Adrenoreceptors, and Shock.

Vasopressors are widely used in the management of shock among critically ill patients. The physiology of vasopressors and adrenoreceptors and their effects on end organs therefore represent important, high-yield topics for learners in the critical care environment. In this report, we describe our approach to teaching this core concept using the stereotypical human physiologic response when running from a bear, in the context of the relevant supporting literature. We use escaping from a threatening predator as a lens to describe the end-organ effects of activating adrenoreceptors together with the effects of endogenous and exogenous catecholamines and vasopressors. After reviewing this foundational physiology, we transition to the clinical environment, reviewing the pathophysiology of various shock states. We then consolidate our teaching by integrating the physiology of adrenoreceptors with the pathophysiology of shock to understand the appropriateness of each therapy to various shock phenotypes. We emphasize to learners the importance of generating a hypothesis about a patient's physiology, testing that hypothesis with an intervention, and then revising the hypothesis as needed, a critical component in the management of critically ill patients.

Powering Bias and Clinically Important Treatment Effects in Randomized Trials of Critical Illness.

OBJECTIVES: Recurring issues in clinical trial design may bias results toward the null, yielding findings inconclusive for treatment effects. This study evaluated for powering bias among high-impact critical care trials and the associated risk of masking clinically important treatment effects. DESIGN, SETTING, AND PATIENTS: Secondary analysis of multicenter randomized trials of critically ill adults in which mortality was the main endpoint. Trials were eligible for inclusion if published between 2008 and 2018 in leading journals. Analyses evaluated for accuracy of estimated control group mortality, adaptive sample size strategy, plausibility of predicted treatment effect, and results relative to the minimal clinically important difference. The main outcome was the mortality risk difference at the study-specific follow-up interval. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 101 included trials, 12 met statistical significance for their main endpoint, five for increased intervention-associated mortality. Most trials (77.3%) overestimated control group mortality in power calculations (observed minus predicted difference, -6.7% ± 9.8%; p < 0.01). Due to this misestimation of control group mortality, in 14 trials, the intervention would have had to prevent at least half of all deaths to achieve the hypothesized treatment effect. Seven trials prespecified adaptive sample size strategies that might have mitigated this issue. The observed risk difference for mortality fell within 5% of predicted in 20 trials, of which 16 did not reach statistical significance. Half of trials (47.0%) were powered for an absolute risk reduction greater than or equal to 10%, but this effect size was observed in only three trials with a statistically significant treatment benefit. Most trials (67.3%) could not exclude clinically important treatment benefit or harm. CONCLUSIONS: The design of most high-impact critical care trials biased results toward the null by overestimating control group mortality and powering for unrealistic treatment effects. Clinically important treatment effects often cannot be excluded.

Reorganizing a Medicine Residency Program in Response to the COVID-19 Pandemic in New York.

The COVID-19 pandemic has been particularly severe in New York City, resulting in a rapid influx of patients into New York-Presbyterian Hospital/Columbia University Irving Medical Center. The challenges precipitated by this pandemic have required urgent changes to existing models of care. Internal medicine residents are at the forefront of caring for patients with COVID-19, including the critically ill. This article describes the exigent restructuring of the New York-Presbyterian Hospital/Columbia University Internal Medicine Residency Program. Patient care and educational models were fundamentally reconceptualized, which required a transition away from traditional hierarchical team structures and a significant expansion in the program's capacity and flexibility to care for large numbers of patients with disproportionately high levels of critical illness. These changes were made while the residency program maintained the priorities of patient care and safety, resident safety and well-being, open communication, and education. The process of adapting the residency program to the demands of the pandemic was iterative given the unprecedented nature of this crisis. The goal of this article is to share the experiences and lessons learned from this crisis, communicate the solutions that were designed, and inform others who may be facing the prospect of creating similar disaster response measures.

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19.

BACKGROUND: Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODS: We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS: Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. CONCLUSIONS: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.).

Treatment of uveal melanoma: where are we now?

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease.

Transthyretin Cardiac Amyloidosis in Older Adults: Optimizing Cardiac Imaging to the Corresponding Diagnostic and Management Goal.

PURPOSE OF REVIEW: Transthyretin cardiac amyloidosis is increasingly recognized as an important cause of heart failure in older adults. Many cardiac imaging modalities have evolved to evaluate transthyretin cardiac amyloidosis and include 2D echocardiography with tissue Doppler and speckle-strain imaging, nuclear scintigraphy, cardiac magnetic resonance imaging, and positron emission tomography. The purpose of this review is to highlight the optimal selection of advanced cardiac imaging techniques with corresponding diagnostic goals including raising suspicion, making an early diagnosis, and subtyping transthyretin cardiac amyloid, as well as management goals including assessment of ventricular impairment, prognosticating, and monitoring disease progression. Potential benefits of optimizing cardiac imaging in the elderly patient with transthyretin cardiac amyloidosis may include enhanced and earlier diagnosis and refined long-term management. RECENT FINDINGS: Advances in cardiac imaging techniques are changing diagnostic and management algorithms for transthyretin cardiac amyloidosis. SUMMARY: With a new era of novel therapeutics, enhanced recognition, and earlier diagnosis approaching, selecting the appropriate non-invasive cardiac imaging modality will be essential for optimal care in the elderly patient with transthyretin cardiac amyloidosis.

An atypical presentation of adult-onset Still's disease complicated by pulmonary hypertension and macrophage activation syndrome treated with immunosuppression: a case-based review of the literature.

Pulmonary arterial hypertension (PAH) is a known complication of rheumatologic diseases, but it is only rarely associated with adult-onset Still's disease (AOSD). We describe the case of a 30-year-old woman who presented in a pulmonary hypertension crisis and was found to have underlying AOSD with PAH and nonspecific interstitial pneumonia (NSIP) with a course complicated by macrophage activation syndrome (MAS). She dramatically improved with steroids, cyclosporine A, and anakinra, with total resolution of the MAS and significant improvement of her pulmonary arterial pressures. While there are only select case reports of AOSD associated with PAH, this is the first reported case of (1) AOSD complicated by both PAH and MAS and (2) AOSD complicated by biopsy-proven NSIP. Clinically, this case highlights the efficacy of immunosuppressive agents in the treatment of PAH and MAS from underlying AOSD and supports their use in this setting.

Selumetinib for the treatment of metastatic uveal melanoma: past and future perspectives.

Uveal melanoma is a rare but aggressive subtype of melanoma. Nearly 50% of patients will develop metastatic disease despite primary enucleation or radiation therapy. There is currently no standard of care therapy for metastatic uveal melanoma, and no therapy that has been shown to prolong overall survival. Uveal melanoma is characterized by activation of signaling pathways including the MAPK pathway and the PI3K/AKT pathway, among others, via mutations in the G-α-proteins GNAQ and GNA11. MEK inhibition with selumetinib has been evaluated as a therapeutic strategy in metastatic uveal melanoma. This review will discuss preclinical and clinical studies evaluating selumetinib in metastatic uveal melanoma, as well as potential future perspectives on MEK inhibition in the management of metastatic uveal melanoma.

Variability in Motor and Language Recovery during the Acute Stroke Period.

BACKGROUND: Most stroke recovery occurs by 90 days after onset, with proportional recovery models showing an achievement of about 70% of the maximal remaining recovery. Little is known about recovery during the acute stroke period. Moreover, data are described for groups, not for individuals. In this observational cohort study, we describe for the first time the daily changes of acute stroke patients with motor and/or language deficits over the first week after stroke onset. METHODS: Patients were enrolled within 24-72 h after stroke onset with upper extremity hemiparesis, aphasia, or both, and were tested daily until day 7 or discharge with the upper-extremity Fugl-Meyer Assessment of Motor Recovery after Stroke, the Boston Naming Test, and the comprehension domain from the Western Aphasia Battery. Discharge scores, and absolute and proportional changes were examined using t-tests for pairwise comparisons and linear regression to determine relative contributions of initial impairment, lesion volume, and age to recovery over this period. RESULTS: Thirty-four patients were enrolled: 19 had motor deficits alone, 8 had aphasia alone, and 7 had motor and language deficits. In a group analysis, statistically significant changes in absolute scores were found in the motor (p < 0.001) and comprehension (p < 0.001) domains but not in naming. Day-by-day recovery curves for individual patients displayed wide variation with comparable initial impairment. Proportional recovery calculations revealed that, on average, patients achieved less than 1/3 of their potential recovery by the time of discharge. Multivariate regression showed that the amount of variance accounted for by initial severity, age, and lesion volume in this early time period was not significant for motor or language domains. CONCLUSIONS: Over the first week after stroke onset, recovery of upper extremity hemiparesis and aphasia were not predictable on the basis of initial impairment, lesion volume, or age. In addition, patients only achieved about 1/3 of their remaining possible recovery based on the anticipated 70% proportion found at 90 days. These findings suggest that the complex interaction between poststroke structural repair, regeneration, and functional reorganization during the first week after stroke has yet to be elucidated.