Preferred Language Mediates Association Between Race, Ethnicity, and Delayed Presentation in Critically Ill Patients With COVID-19.

Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear. OBJECTIVES: We hypothesized that preferred language mediates the association between race, ethnicity and delays to care. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020. MAIN OUTCOME AND MEASURES: Causal mediation analysis was performed to evaluate potential mediators including preferred language, insurance status, and neighborhood characteristics. RESULTS: Non-Hispanic White (NHW) patients (157/442, 36%) were more likely to speak English as their preferred language (78% vs. 13%), were less likely to be un- or under-insured (1% vs. 28%), lived in neighborhoods with lower social vulnerability index (SVI) than patients from racial and ethnic minority groups (SVI percentile 59 [28] vs. 74 [21]) but had more comorbidities (Charlson comorbidity index 4.6 [2.5] vs. 3.0 [2.5]), and were older (70 [13.2] vs. 58 [15.1] years). From symptom onset, NHW patients were admitted 1.67 [0.71-2.63] days earlier than patients from racial and ethnic minority groups (p < 0.01). Non-English preferred language was associated with delay to admission of 1.29 [0.40-2.18] days (p < 0.01). Preferred language mediated 63% of the total effect (p = 0.02) between race, ethnicity and days from symptom onset to hospital admission. Insurance status, social vulnerability, and distance to the hospital were not on the causal pathway between race, ethnicity and delay to admission. CONCLUSIONS AND RELEVANCE: Preferred language mediates the association between race, ethnicity and delays to presentation for critically ill patients with COVID-19, although our results are limited by possible collider stratification bias. Effective COVID-19 treatments require early diagnosis, and delays are associated with increased mortality. Further research on the role preferred language plays in racial and ethnic disparities may identify effective solutions for equitable care.

Prolonged Prone Position Ventilation Is Associated With Reduced Mortality in Intubated COVID-19 Patients.

BACKGROUND: Prone position ventilation (PPV) is resource-intensive, yet the optimal strategy for PPV in intubated patients with COVID-19 is unclear. RESEARCH QUESTION: Does a prolonged (24 or more h) PPV strategy improve mortality in intubated COVID-19 patients compared with intermittent (∼16 h with daily supination) PPV? STUDY DESIGN AND METHODS: Multicenter, retrospective cohort study of consecutively admitted intubated COVID-19 patients treated with PPV between March 11 and May 31, 2020. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 90-day all-cause mortality and prone-related complications. Inverse probability treatment weights (IPTW) were used to control for potential treatment selection bias. RESULTS: Of the COVID-19 patients who received PPV, 157 underwent prolonged and 110 underwent intermittent PPV. Patients undergoing prolonged PPV had reduced 30-day (adjusted hazard ratio [aHR], 0.475; 95% CI, 0.336-0.670; P < .001) and 90-day (aHR, 0.638; 95% CI, 0.461-0.883; P = .006) mortality compared with intermittent PPV. In patients with Pao2/Fio2 ≤ 150 at the time of pronation, prolonged PPV was associated with reduced 30-day (aHR, 0.357; 95% CI, 0.213-0.597; P < .001) and 90-day mortality (aHR, 0.562; 95% CI, 0.357-0.884; P = .008). Patients treated with prolonged PPV underwent fewer pronation and supination events (median, 1; 95% CI, 1-2 vs 3; 95% CI, 1-4; P < .001). PPV strategy was not associated with overall PPV-related complications, although patients receiving prolonged PPV had increased rates of facial edema and lower rates of peri-proning hypotension. INTERPRETATION: Among intubated COVID-19 patients who received PPV, prolonged PPV was associated with reduced mortality. Prolonged PPV was associated with fewer pronation and supination events and a small increase in rates of facial edema. These findings suggest that prolonged PPV is a safe, effective strategy for mortality reduction in intubated COVID-19 patients.

Spontaneous haematomas and haematochezia due to vitamin C deficiency in a haemodialysis patient.

A man in his 50s with dialysis-dependent end-stage renal disease, several weeks history of progressive skin bruising and acute-onset gastrointestinal bleeding presented to the emergency department following a syncopal event during routine haemodialysis owing to profound hypotension. He was found to have a severe normocytic, normochromic anaemia requiring several blood transfusions. He followed a diet lacking fruits and vegetables and stopped taking renal multivitamins. All parameters of coagulation were unremarkable, but serum vitamin C level was undetectable, supporting a diagnosis of scurvy. Although typically associated with individuals who are at risk of malnourishment, such as those with alcohol use disorder, malabsorption, and those who experience homelessness, scurvy should be considered in patients receiving renal replacement therapy as vitamin C is removed during haemodialysis.

Code status orders in patients admitted to the intensive care unit with COVID-19: A retrospective cohort study.

Purpose: Code status orders impact clinical outcomes as well as patients' and surrogates' experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported to date. Materials and methods: This is a retrospective cohort study including adult patients who tested positive for SARS-CoV-2 and were admitted to the ICU at three hospitals in Massachusetts from March 11, 2020 - May 31, 2020. We examined differences in code status orders at multiple timepoints and performed multivariable regression analysis to identify variables associated with code status at admission. Results: Among 459 ICU patients with COVID-19, 421 (91.7%) were Full Code at hospital admission. Age and admission from a facility were positively associated with DNR status (adjusted OR 1.10, 95% CI 1.05-1.15, p < 0.001 and adjusted OR 2.68, CI 1.23-5.71, p = 0.011, respectively) while non-English preferred language was negatively associated with DNR status (adjusted OR 0.29, 95% CI 0.10-0.74, p = 0.012). Among 147 patients who died during hospitalization, 95.2% (140) died with DNR code status; most (86.4%) died within two days of final code status change. Conclusions: The association of non-English preferred language with Full Code status in critically ill COVID-19 patients highlights the importance of medical interpreters in the ICU. Patients who died were transitioned to DNR more than in previous studies, possibly reflecting changes in practice during a novel pandemic.

Timing of Postdischarge Follow-Up and Medication Adherence Among Patients With Heart Failure.

BACKGROUND: Medication adherence improves outcomes for patients with heart failure, but adherence rates remain low. We examined the association between earlier postdischarge follow-up and medication adherence. METHODS AND RESULTS: We performed a retrospective cohort study of patients ≥65 years who were hospitalized for heart failure, covered by Medicare Part D, and discharged alive from April 2006 to October 2012 using the Get With The Guidelines-Heart Failure Registry linked to Medicare claims. Patients were categorized into 4 groups by timing of first postdischarge follow-up visit: ≤1, 1 to 2, 2 to 6, and >6 weeks. Medication adherence was defined by proportion of days covered of >80% at 90 days and 1-year posthospital discharge to 5 guideline-directed medical therapies (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, evidence-based ß-blocker, aldosterone antagonist, hydralazine/isosorbide dinitrate, and anticoagulation for atrial fibrillation). Among 9878 patients with heart failure, 73% had left ventricular ejection fraction ≤40%, median age was 78 years (25th-75th percentile, 71-84), and 48% were male. Overall, 30% had a follow-up appointment within 1-week postdischarge and 25% >6 weeks. At 1 year, medication adherence was 53% for evidence-based ß-blockers, 48% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 8% for hydralazine/isosorbide dinitrate. We found no significant association between timing of first follow-up visit and medication adherence at 1 year (1.04, 0.92-1.17) when comparing follow-up visits >6 weeks to the earliest ones. CONCLUSIONS: Posthospital heart failure discharge, overall adherence to medical therapies in Medicare beneficiaries was low. Early follow-up was not associated with increased medication adherence to guideline-directed medical therapy in the short or long term.

Is it a match? a novel method of evaluating medical school success.

BACKGROUND: Medical education program evaluation allows for curricular improvements to both Undergraduate (UME) and Graduate Medical Education (GME). UME programs are left with little more than match rates and self-report to evaluate success of graduates in The Match. OBJECTIVE: This manuscript shares a novel method of program evaluation through a systematic assessment of Match outcomes. DESIGN: Surveys were developed and distributed to Program Training Directors (PTDs) at our institution to classify residency programs into which our UME graduates matched using an ordinal response scale and open-ended responses. Outcomes-based measures for UME graduates were collected and analyzed. The relationship between PTD survey data and UME graduates' outcomes were explored. Open-ended response data were qualitatively analyzed using iterative cycles of coding and identifying themes. RESULTS: The PTD survey response rate was 100%. 71% of our graduates matched to programs ranked as 'elite' (36%) or 'top' (35%) tier. The mean total number of 'Honors' grades achieved by UME graduates was 2.6. Data showed that graduates entering elite and top GME programs did not consistently earn Honors in their associated clerkships. A positive correlation was identified between USMLE Step 1 score, number of honors, and residency program rankings for a majority of the programs. Qualitative analysis identified research, faculty, and clinical exposure as necessary characteristics of 'elite' programs:. Factors considered by PTDs in the rating of programs included reputation, faculty, research, national presence and quality of graduates. CONCLUSIONS: This study describes a novel outcomes-based method of evaluating the success of UME programs. Results provided useful feedback about the quality of our UME program and its ability to produce graduates who match in highly-regarded GME programs. The findings from this study can benefit Clerkship Directors, Student Affairs and Curriculam Deans, and residency PTDs as they help students determine their competitiveness forspecialties and specific residency programs.

Leveraging Behavioral Economics to Improve Heart Failure Care and Outcomes.

Behavioral challenges are often present in human illness, so behavioral economics is increasingly being applied in healthcare settings to better understand why patients choose healthy or unhealthy behaviors. The application of behavioral economics to healthcare settings parallels recent shifts in policy and reimbursement structures that hold providers accountable for outcomes that are dependent on patient behaviors. Numerous studies have examined the application of behavioral economics principles to policy making and health behaviors, but there are limited data on applying these concepts to the management of chronic conditions, such as heart failure (HF). Given its increasing prevalence and high associated cost of care, HF is a paradigm case for studying novel approaches to improve health care; therefore, if we can better understand why patients with HF make the choices they do, then we may be more poised to help them manage their medications, influence daily behaviors, and encourage healthy decision making. In this article, we will give a brief explanation of the core behavioral economics concepts that apply to patients with HF. We will also examine how to craft these concepts into tools such as financial incentives and social networks that may improve the management of patients with HF. We believe that behavioral economics can help us understand barriers to change, encourage positive behaviors, and offer additional approaches to improving the outcomes of patients with HF.

Discovery of a substrate selectivity motif in amino acid decarboxylases unveils a taurine biosynthesis pathway in prokaryotes.

Taurine, the most abundant free amino acid in mammals, with many critical roles such as neuronal development, had so far only been reported to be synthetized in eukaryotes. Taurine is the major product of cysteine metabolism in mammals, and its biosynthetic pathway consists of cysteine dioxygenase and cysteine sulfinic acid decarboxylase (hCSAD). Sequence, structural, and mutational analyses of the structurally and sequentially related hCSAD and human glutamic acid decarboxylase (hGAD) enzymes revealed a three residue substrate recognition motif (X1aa19X2aaX3), within the active site that is responsible for coordinating their respective preferred amino acid substrates. Introduction of the cysteine sulfinic acid (CSA) motif into hGAD (hGAD-S192F/N212S/F214Y) resulted in an enzyme with a >700 fold switch in selectivity toward the decarboxylation of CSA over its preferred substrate, l-glutamic acid. Surprisingly, we found this CSA recognition motif in the genome sequences of several marine bacteria, prompting us to evaluate the catalytic properties of bacterial amino acid decarboxylases that were predicted by sequence motif to decarboxylate CSA but had been annotated as GAD enzymes. We show that CSAD from Synechococcus sp. PCC 7335 specifically decarboxylated CSA and that the bacteria accumulated intracellular taurine. The fact that CSAD homologues exist in certain bacteria and are frequently found in operons containing the recently discovered bacterial cysteine dioxygenases that oxidize l-cysteine to CSA supports the idea that a bona fide bacterial taurine biosynthetic pathway exists in prokaryotes.

p53-mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer.

Studies on the role of TP53 mutation in breast cancer response to chemotherapy are conflicting. Here, we show that, contrary to dogma, MMTV-Wnt1 mammary tumors with mutant p53 exhibited a superior clinical response compared to tumors with wild-type p53. Doxorubicin-treated p53 mutant tumors failed to arrest proliferation, leading to abnormal mitoses and cell death, whereas p53 wild-type tumors arrested, avoiding mitotic catastrophe. Senescent tumor cells persisted, secreting senescence-associated cytokines exhibiting autocrine/paracrine activity and mitogenic potential. Wild-type p53 still mediated arrest and inhibited drug response even in the context of heterozygous p53 point mutations or absence of p21. Thus, we show that wild-type p53 activity hinders chemotherapy response and demonstrate the need to reassess the paradigm for p53 in cancer therapy.