Faculty Bibliography

Introduction/UNASSIGNED:The combination of hydralazine-isosorbide dinitrate (H-ISDN) has potential as a heart failure (HF) therapy in the setting of maintenance dialysis. Methods/UNASSIGNED:In this retrospective study, we analyzed the efficacy of H-ISDN using United States Renal Data System (USRDS) data. We identified all adult patients with a history of HF on maintenance dialysis between January 1, 2011, and December 31, 2016, with at least 1 prescription for H-ISDN. Baseline characteristics, prescriptions, and outcomes were retrieved from institutional and physician claims. The primary outcome was death from any cause. Additional outcomes included cardiovascular death, sudden cardiac death, hospitalization for HF, an inpatient diagnosis of myocardial infarction (MI), or new-onset atrial fibrillation. Stabilized inverse probability weights were estimated using relevant baseline characteristics and were used in Cox proportional hazards regression. Results/UNASSIGNED:We identified 6306 patients who were treated with H-ISDN and 75,509 patients who did not receive H-ISDN. The crude all-cause mortality rate was lower in patients treated with H-ISDN (16.0 events/100 patient years [PYs]) than in nonusers (27.9/100-PY). H-ISDN use was independently associated with lower mortality: hazard ratio (HR) 0.48 (95% CI 0.43-0.54). Cardiovascular death and sudden cardiac death were less common among H-ISDN users than nonusers, Weighted HR was 0.62 (95% CI 0.53-0.71) and 0.62 (95% CI 0.52-0.73), respectively. In contrast, HF admission and MI were more frequent in patients treated with H-ISDN (195.5 and 18.0 events/100-PY) compared with nonusers (73.4 and 10.2 events/100-PY). Conclusion/UNASSIGNED:H-ISDN therapy may improve cardiovascular outcomes in maintenance dialysis patients with HF.

BACKGROUND: Central nervous system (CNS) germinomas are commonly located in the suprasellar and/or pineal regions. Current treatment strategies include irradiation (RT) alone or chemotherapy with RT to reduce the dose and field of RT. However, given their rarity and poorly defined imaging characteristics, germinomas originating in the basal ganglia/ thalami (BGTG) have proven challenging to treat. We present a case series of six patients with metastatic BGTG, given the paucity of published research on patients with metastatic CNS BGTG.
METHOD(S): A retrospective multi-institutional review was performed across four institutions in two countries.
RESULT(S): Two patients were females, and four were males. The median age at presentation was 14.9 years. Biopsies were performed in all patients except for one patient who underwent subtotal surgical resection of her primary tumor. Three patients received RT only, while the remaining three received chemotherapy with RT. Carboplatin and etoposide were used in all three patients who received chemotherapy. All six patients received craniospinal irradiation (CSI). For patients who received RT only, the CSI dose ranged between (24 -27.2 Gy) with a total dose to the primary site ranging between (36 -40 Gy). For patients who received chemotherapy, one patient received 36 Gy with a total dose of 54 Gy to the primary site. The second patient received 24 Gy with a total dose of 40 Gy to the primary site. The CSI dose was not available for the third patient. All patients remain alive with a median event-free survival (EFS) and overall survival (OS) of 49 months (range: 14.3 -168 months).
CONCLUSION(S): In our series, patients with metastatic CNS BGTG treated with CSI with or without chemotherapy had excellent outcomes. Future larger studies are needed to compare the outcomes between CSI only and chemotherapy with low-dose CSI among patients with metastatic CNS BGTG

BACKGROUND:Hospitalist physicians' workload-the total number of patients they care for daily-is rising in the U.S. Hospitalists report that increased workload negatively affects patients care. OBJECTIVE:Measure the associations between hospitalist physicians' workload and clinical outcomes. DESIGN, SETTINGS, AND PARTICIPANTS/METHODS:Observational study, using electronic health record (EHR) data, of adults hospitalized on the hospitalist service at Yale-New Haven Hospital from 2015-2018. MAIN OUTCOME AND MEASURES/METHODS:We defined hospitalists' workload as the number of patients they cared for on the first full hospital day of a given patient's encounter. We used multilevel Poisson and logistic regression to examine associations between workload and length of stay (LOS), return to the Emergency Department (ED), and readmission. We adjusted for sociodemographic factors, patient complexity and severity of illness, and weekend admission (for LOS) or discharge (for ED visits or readmission). RESULTS:We analyzed 38,141 hospitalizations. Median patient age was 64 years (IQR 51-78 years), 53% were female, and 34% were nonwhite. Mean workload was 15 patients (SD 3 patients; range 10-34 patients). LOS was prolonged by 0.05 days (95% CI 0.02, 0.08; p(0.001) when comparing the 75th workload percentile (16 patients) to the 25th workload percentile (13 patients). There were no associations between workload and ED visits or readmission within 7 and 30 days. CONCLUSIONS:There was a statistically significant but modest relationship between workload and LOS; workload was not associated with ED visits or readmissions.Given clinical reports of the deleterious effects of increased hospitalist workload, there is a need for prospective research assessing a range of outcomes, beyond those measurable in contemporary EHR data.

AIM/OBJECTIVE:To study the relationship between Polish nurses' working conditions and their attitudes towards patient safety during the COVID-19 pandemic. BACKGROUND:Facing the COVID-19 pandemic, caused by the SARS-CoV-2 virus, healthcare worldwide has been reorganised. How these changes affected patient safety for hospitalised persons is not well understood. INTRODUCTION/BACKGROUND:Difficult working conditions related to the outbreak of the COVID-19 pandemic may affect the provision of safe and effective care by healthcare staff. METHODS:This observational research was performed on the group of 577 nurses working during the COVID-19 pandemic in isolation infection wards (n = 201) and non-infectious diseases wards (n = 376) in Polish hospitals. The evaluation of working conditions was performed with an author's questionnaire, while the evaluation of factors influencing attitudes towards safety of the hospitalised patients was performed using Safety Attitudes Questionnaire. The STROBE checklist was used to report this study. RESULTS:The procedures developed by management in advance for COVID-19 patient treatment had a statistically significant influence on nurses' 'evaluation of teamwork climate, safety climate, job satisfaction, perception of management and work conditions'. Providing management with the ability to perform a swab polymerase chain reaction SARS-CoV-2 test for hospital staff in the workplace, and psychological support from professionals and employers were statistically significant for higher ratings of 'teamwork climate, safety climate, job satisfaction, stress recognition, perception of management and work conditions' by the Polish nurses. Hospital workload during the COVID-19 pandemic was significantly correlated with lower evaluation of work conditions. DISCUSSION/CONCLUSIONS:Our study reinforces the existing literature on many fronts and demonstrates how even when operating under the COVID-19 pandemic conditions, some factors remain critical for fostering a culture of patient safety. Reinforcing patient safety practices is a imperative under these conditions. CONCLUSIONS AND IMPLICATIONS FOR NURSING/UNASSIGNED:Working conditions influence nurses' attitudes towards safety of the hospitalised patients. These are largely modifiable factors related to the workplace and include prior preparation of procedures, restrictions to extending daily work hours and psychological counselling for the staff.

This second paper in a 3-part series on antiracism in pain research across the translational spectrum focuses on study design factors. Although objectivity is a cornerstone value of science, subjectivity is embedded in every step of the research process as investigators make choices about who they collaborate with, which research questions they ask, how they recruit participants, which research tools they use, and how they analyze and interpret data. We present theory and evidence from disciplines such as sociology, medical anthropology, statistics, and public health to discuss 4 common study design factors, including 1) the dominant biomedical narrative of pain that restricts funding and exploration of social indicators of pain, 2) low diversity and inclusion in pain research enrollment that restricts generalizability to racialized groups, 3) the use of "race" or "ethnicity" as a statistical variable and proxy for lived experiences (eg, racism, resilience), and 4) limited modeling in preclinical research for the impact of social factors on pain physiology. The information presented in this article is intended to start conversations across stakeholders in the pain field to explore how we can come together to adopt antiracism practices in our work at large to achieve equity for racialized groups. PERSPECTIVE: This is the second paper in a 3-part series on antiracism in pain research. This part identifies common study design factors that risk hindering progress toward pain care equity. We suggest reframes using an antiracism framework for these factors to encourage all pain investigators to collectively make strides toward equity.

Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR=29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in anti-viral immunity. BACKGROUND: We find that a number of IFN pathway lupus risk alleles significantly impact mortality following COVID-19 infection. These data support the idea that type I IFN pathway risk alleles for autoimmune disease may persist in high frequency in modern human populations due to a benefit in our defense against viral infections. TRANSLATIONAL SIGNIFICANCE: We develop multivariate prediction models which combine genetics and known biomarkers of severity to result in greatly improved prediction of mortality in acute COVID-19. The specific associated alleles provide some clues about key points in our defense against COVID-19.

OBJECTIVE:To characterise inflammatory bowel disease (IBD) trends and associated risk during delivery hospitalisations. DESIGN/METHODS:Cross-sectional. SETTING/METHODS:US delivery hospitalisations. POPULATION/METHODS:Delivery hospitalisations in the 2000-2018 National Inpatient Sample. METHODS:This study analysed a nationally representative hospital discharge database based on the presence of IBD. Temporal trends in IBD were analysed using joinpoint regression to estimate the average annual percent change (AAPC). IBD severity was characterised by the presence of diagnoses such as penetrating and stricturing disease and history of bowel resection. Risks for adverse outcomes were analysed based on presence of IBD. Poisson regression models were performed with unadjusted and adjusted risk ratios (aRR) as measures of effect. MAIN OUTCOME MEASURE/METHODS:Prevalence of IBD and associated adverse outcomes. RESULTS:Of 73 109 790 delivery hospitalisations, 89 965 had a diagnosis of IBD. IBD rose from 0.06% in 2000 to 0.21% in 2018 (AAPC 7.3%, 95% CI 6.7-7.9%). Among deliveries with IBD, IBD severity diagnoses increased from 4.1% to 8.1% from 2000 to 2018. In adjusted analysis, IBD was associated with increased risk for preterm delivery (aRR 1.50, 95% CI 1.47-1.53), severe maternal morbidity (aRR 1.93, 95% CI 1.83-2.04), venous thrombo-embolism (aRR 2.76, 95% CI 2.39-3.18) and surgical injury during caesarean delivery hospitalisation (aRR 5.03, 95% CI 4.76-5.31). In the presence of a severe IBD diagnosis, risk was further increased for all adverse outcomes. CONCLUSION/CONCLUSIONS:IBD is increasing in the obstetric population and is associated with adverse outcomes. Risk is increased in the presence of a severe IBD diagnosis. TWEETABLE ABSTRACT/UNASSIGNED:Deliveries among women with inflammatory bowel disease are increasing. Disease severity is associated with adverse outcomes.