BACKGROUND: Hospitalists frequently work on diverse projects, but often do not have the training and experience necessary to translate projects into peer-reviewed publications and grants. OBJECTIVE: Describe implementation and effect of a works-in-progress (WIP) series on progress and training in scholarly work. DESIGN: Cross-sectional survey. SETTING: Urban academic medical center. INTERVENTION: A weekly WIP session, named Incubator, serving as a forum where researchers, clinicians, and educators meet to review and provide feedback on projects underway across the Division of Hospital Medicine. MEASUREMENTS: We surveyed presenters at Incubator to evaluate the impact of Incubator on scholarly activities. Responses were based on Kirkpatricks 4-level training hierarchy: (1) Reaction: participants satisfaction; (2) Learning: knowledge acquisition; (3) Behavior: application of skills; and (4) Results of projects. We compared responses between researchers and nonresearchers using χ2 tests. RESULTS: Of 51 surveys completed (response rate 70%), 35 (69%) projects were nonresearcher led. Reaction, behavior change, and results were all positive, with >90% respondents reporting a positive outcome in each category, a high rate of publication/funding, and 35% reporting learning as a result of Incubator. Comparison of researchers and nonresearchers revealed no significant differences, except nonresearchers reported significantly more favorable results in behavior and mentoring (P < 0.05). DISCUSSION: A regularly scheduled, researcher-led WIP session within a largely clinically oriented hospital medicine division can provide a venue for feedback that may promote progress and practical training in scholarly projects. In addition to robust career mentorship programs and protected time, a WIP can be an adjunct to improve scholarly output among academic hospitalists. Journal of Hospital Medicine 2016;11:719-723. © 2016 Society of Hospital Medicine.

Hopelessness is associated with mortality in patients with cardiac disease even after accounting for severity of depression. We sought to determine whether a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with increased hopelessness, and whether this effect is modified by sex, age, antidepressant use or depression in patients with coronary heart disease. We conducted a cross-sectional study of 870 patients with stable coronary heart disease. Our primary outcomes were hopelessness score (range 0-8) and hopeless category (low, moderate and high) as measured by the Everson hopelessness scale. Analysis of covariance and ordinal logistic regression were used to examine the independent association of genotype with hopelessness. Compared to patients with l/l genotype, adjusted odds of a higher hopeless category increased by 35% for the l/s genotype and 80% for s/s genotype (p-value for trend = 0.004). Analysis of covariance demonstrated that the effect of 5-HTTLPR genotype on hopelessness was modified by sex (.04), but not by racial group (p = 0.63). Among men, odds of higher hopeless category increased by 40% for the l/s genotype and by 2.3-fold for s/s genotype (p-value p < 0.001), compared to no effect in the smaller female sample (p = 0.42). Results stratified by race demonstrated a similar dose-response effect of the s allele on hopelessness across racial groups. We found that the 5-HTTLPR is independently associated with hopelessness among men with cardiovascular disease.

Purpose

We recently identified interleukin-27 (IL-27) as a sepsis diagnostic biomarker in children. Here we assess IL-27 as a sepsis diagnostic biomarker in critically ill adults with systemic inflammatory response syndrome and sepsis.

Methods

IL-27 and procalcitonin (PCT) were measured from plasma samples in three groups: no sepsis (n = 78), pulmonary source of sepsis (n = 66), and non-pulmonary source of sepsis (n = 43). Receiver operating characteristic curves and classification and regression tree methodology were used to evaluate biomarker performance.

Results

IL-27 did not discriminate effectively between sepsis and sterile systemic inflammatory response syndrome in unselected patients. The highest area under the curve (AUC) was 0.70 (95% C.I. 0.60 - 0.80) for IL-27 in subjects with a non-pulmonary source of sepsis. A decision tree incorporating IL-27, PCT, and age had an AUC of 0.79 (0.71-0.87) in subjects with a non-pulmonary source of sepsis. Compared to children with sepsis, adults with sepsis express less IL-27.

Conclusions

IL-27 performed overall poorly in this cohort as a sepsis diagnostic biomarker. Combining IL-27, PCT, and age reasonably estimated the risk of sepsis in subjects with a non-pulmonary source of sepsis. IL-27 may be a more reliable sepsis diagnostic biomarker in children than in adults.

OBJECTIVES:Early identification of sepsis is critical to improving patient outcomes. Impact of the new sepsis definition (Sepsis-3) on timing of recognition in the emergency department has not been evaluated. Our study objective was to compare time to meeting systemic inflammatory response syndrome (Sepsis-2) criteria, Sequential Organ Failure Assessment (Sepsis-3) criteria, and quick Sequential Organ Failure Assessment criteria using electronic health record data. DESIGN:Retrospective, observational study. SETTING:The emergency department at the University of California, San Francisco. PATIENTS:Emergency department encounters between June 2012 and December 2016 for patients greater than or equal to 18 years old with blood cultures ordered, IV antibiotic receipt, and identification with sepsis via systemic inflammatory response syndrome or Sequential Organ Failure Assessment within 72 hours of emergency department presentation. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We analyzed timestamped electronic health record data from 16,612 encounters identified as sepsis by greater than or equal to 2 systemic inflammatory response syndrome criteria or a Sequential Organ Failure Assessment score greater than or equal to 2. The primary outcome was time from emergency department presentation to meeting greater than or equal to 2 systemic inflammatory response syndrome criteria, Sequential Organ Failure Assessment greater than or equal to 2, and/or greater than or equal to 2 quick Sequential Organ Failure Assessment criteria. There were 9,087 patients (54.7%) that met systemic inflammatory response syndrome-first a median of 26 minutes post-emergency department presentation (interquartile range, 0-109 min), with 83.1% meeting Sequential Organ Failure Assessment criteria a median of 118 minutes later (interquartile range, 44-401 min). There were 7,037 patients (42.3%) that met Sequential Organ Failure Assessment-first, a median of 113 minutes post-emergency department presentation (interquartile range, 60-251 min). Quick Sequential Organ Failure Assessment was met in 46.4% of patients a median of 351 minutes post-emergency department presentation (interquartile range, 67-1,165 min). Adjusted odds of in-hospital mortality were 39% greater in patients who met systemic inflammatory response syndrome-first compared with those who met Sequential Organ Failure Assessment-first (odds ratio, 1.39; 95% CI, 1.20-1.61). CONCLUSIONS:Systemic inflammatory response syndrome and Sequential Organ Failure Assessment initially identified distinct populations. Using systemic inflammatory response syndrome resulted in earlier electronic health record sepsis identification in greater than 50% of patients. Using Sequential Organ Failure Assessment alone may delay identification. Using systemic inflammatory response syndrome alone may lead to missed sepsis presenting as acute organ dysfunction. Thus, a combination of inflammatory (systemic inflammatory response syndrome) and organ dysfunction (Sequential Organ Failure Assessment) criteria may enhance timely electronic health record-based sepsis identification.

Background

Hopelessness is associated with mortality in patients with cardiac disease even after accounting for severity of depression. We sought to determine whether a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with increased hopelessness, and whether this effect is modified by sex, age, antidepressant use or depression in patients with coronary heart disease.

Methods

We conducted a cross-sectional study of 870 patients with stable coronary heart disease. Our primary outcomes were hopelessness score (range 0-8) and hopeless category (low, moderate and high) as measured by the Everson hopelessness scale. Analysis of covariance and ordinal logistic regression were used to examine the independent association of genotype with hopelessness.

Results

Compared to patients with l/l genotype, adjusted odds of a higher hopeless category increased by 35% for the l/s genotype and 80% for s/s genotype (p-value for trend = 0.004). Analysis of covariance demonstrated that the effect of 5-HTTLPR genotype on hopelessness was modified by sex (.04), but not by racial group (p = 0.63). Among men, odds of higher hopeless category increased by 40% for the l/s genotype and by 2.3-fold for s/s genotype (p-value p < 0.001), compared to no effect in the smaller female sample (p = 0.42). Results stratified by race demonstrated a similar dose-response effect of the s allele on hopelessness across racial groups.

Conclusions

We found that the 5-HTTLPR is independently associated with hopelessness among men with cardiovascular disease.

BACKGROUND: The Lung Injury Score (LIS) remains a commonly utilized measure of lung injury severity though the additive value of LIS to predict ARDS outcomes over the recent Berlin definition of ARDS, which incorporates severity, is not known. METHODS: We tested the association of LIS (in which scores range from 0 to 4, with higher scores indicating more severe lung injury) and its four components calculated on the day of ARDS diagnosis with ARDS morbidity and mortality in a large, multi-ICU cohort of patients with Berlin-defined ARDS. Receiver Operator Characteristic (ROC) curves were generated to compare the predictive validity of LIS for mortality to Berlin stages of severity (mild, moderate and severe). RESULTS: In 550 ARDS patients, a one-point increase in LIS was associated with 58% increased odds of in-hospital death (95% CI 14 to 219%, P = 0.006), a 7% reduction in ventilator-free days (95% CI 2 to 13%, P = 0.01), and, among patients surviving hospitalization, a 25% increase in days of mechanical ventilation (95% CI 9 to 43%, P = 0.001) and a 16% increase (95% CI 2 to 31%, P = 0.02) in the number of ICU days. However, the mean LIS was only 0.2 points higher (95% CI 0.1 to 0.3) among those who died compared to those who lived. Berlin stages of severity were highly correlated with LIS (Spearmans rho 0.72, P < 0.0001) and were also significantly associated with ARDS mortality and similar morbidity measures. The predictive validity of LIS for mortality was similar to Berlin stages of severity with an area under the curve of 0.58 compared to 0.60, respectively (P-value 0.49). CONCLUSIONS: In a large, multi-ICU cohort of patients with ARDS, both LIS and the Berlin definition severity stages were associated with increased in-hospital morbidity and mortality. However, predictive validity of both scores was marginal, and there was no additive value of LIS over Berlin. Although neither LIS nor the Berlin definition were designed to prognosticate outcomes, these findings suggest that the role of LIS in characterizing lung injury severity in the era of the Berlin definition ARDS may be limited.

Background

Genotype-guided initial warfarin dosing may reduce over-anticoagulation and serious bleeding compared to a one-dose-fits-all dosing method.

Objective

The objective of this review was to investigate the safety and efficacy of genotype-guided dosing of warfarin in reducing the occurrence of serious bleeding events and over-anticoagulation.

Data sources

The authors searched PubMed, EMBASE and International Pharmaceutical Abstracts through January 23, 2009, without language restrictions. Selected articles were randomized trials comparing pharmacogenetic dosing of warfarin versus a "standard" dose control algorithm in adult patients taking warfarin for the first time.

Review methods

Two reviewers independently extracted data and assessed study quality using a validated instrument. The primary outcomes were major bleeding and time spent within the therapeutic range International Normalized Ratio (INR). Secondary outcomes included minor bleeding, thrombotic events and other measures of anticoagulation quality.

Results

Three of 2,014 studies (423 patients) met the inclusion and exclusion criteria. Differences in study quality, dosing algorithms, length of follow-up and outcome measures limited meta-analysis. Summary estimates revealed no statistically significant difference in bleeding rates or time within the therapeutic range INR. The highest quality study found no significant difference in primary or secondary outcomes, although there was a trend towards more rapid achievement of a stable dose (14.1 vs. 19.6 days, p = 0.07) in the pharmocogenetic arm.

Conclusions

We did not find sufficient evidence to support the use of pharmacogenetics to guide warfarin therapy. Additional clinical trials are needed to define the optimal approach to use warfarin pharmacogenetics in clinical practice.

Genotype-guided initial warfarin dosing may reduce over-anticoagulation and serious bleeding compared to a one-dose-fits-all dosing method. The objective of this review was to investigate the safety and efficacy of genotype-guided dosing of warfarin in reducing the occurrence of serious bleeding events and over-anticoagulation. The authors searched PubMed, EMBASE and International Pharmaceutical Abstracts through January 23, 2009, without language restrictions. Selected articles were randomized trials comparing pharmacogenetic dosing of warfarin versus a “standard” dose control algorithm in adult patients taking warfarin for the first time. Two reviewers independently extracted data and assessed study quality using a validated instrument. The primary outcomes were major bleeding and time spent within the therapeutic range International Normalized Ratio (INR). Secondary outcomes included minor bleeding, thrombotic events and other measures of anticoagulation quality. Three of 2,014 studies (423 patients) met the inclusion and exclusion criteria. Differences in study quality, dosing algorithms, length of follow-up and outcome measures limited meta-analysis. Summary estimates revealed no statistically significant difference in bleeding rates or time within the therapeutic range INR. The highest quality study found no significant difference in primary or secondary outcomes, although there was a trend towards more rapid achievement of a stable dose (14.1 vs. 19.6 days, p = 0.07) in the pharmocogenetic arm. We did not find sufficient evidence to support the use of pharmacogenetics to guide warfarin therapy. Additional clinical trials are needed to define the optimal approach to use warfarin pharmacogenetics in clinical practice.

Background

Sepsis progresses rapidly and is associated with considerable morbidity and mortality. Bedside risk stratification scores can quickly identify patients at greatest risk of poor outcomes; however, there is lack of consensus on the best scale to use.

Objective

To compare the ability of quick Sequential Organ Failure Assessment (qSOFA), the National Early Warning System (NEWS2), and the Shock Index-which does not require mental status assessment-to predict poor outcomes among patients with suspected sepsis during triage.

Design, setting, and participants

Retrospective cohort study of adults presenting to an academic emergency department (ED) from June 2012 to December 2018 who had blood cultures and intravenous antibiotics within 24 hours.

Main outcomes and measures

Clinical data were collected from the electronic health record. Patients were considered positive at qSOFA ≥2, Shock Index >0.7, or NEWS2 ≥5 scores. We calculated test characteristics and area under the receiver operating characteristics curves (AUROCs) to predict in-hospital mortality and ED-to-intensive care unit (ICU) admission.

Results

We included 23,837 ED patients; 1,921(8.1%) were qSOFA-positive, 4,273 (17.9%) Shock Index-positive, and 11,832 (49.6%) NEWS2-positive. There were 1,427 (6.0%) deaths and 3,149 (13.2%) ED-to-ICU admissions in the sample. NEWS2 had the highest sensitivity for in-hospital mortality (76.0%) and ED-to-ICU admission (78.9%). qSOFA had the highest specificity for in-hospital mortality (93.4%) and ED-to-ICU admission (95.2%). Shock Index exhibited the highest AUROC for in-hospital mortality (0.648; 95 CI, 0.635-0.662) and ED-to-ICU admission (0.680; 95% CI, 0.617-0.689). Test characteristics were similar among those with sepsis.

Conclusions

Institution priorities should drive score selection, balancing sensitivity and specificity. In our study, qSOFA was highly specific and NEWS2 was the most sensitive for ruling out patients at high risk. Performance of the Shock Index fell between qSOFA and NEWS2 and could be considered because it is easy to implement.

Background

Limited English proficiency (LEP) has been implicated in poor health outcomes. Sepsis is a frequently fatal syndrome that is commonly encountered in hospital medicine. The impact of LEP on sepsis mortality is not currently known.

Objective

To determine the association between LEP and sepsis mortality.

Design

Retrospective cohort study.

Setting

800-bed, tertiary care, academic medical center.

Patients

Electronic health record data were obtained for adults admitted to the hospital with sepsis between June 1, 2012 and December 31, 2016.

Measurements

The primary predictor was LEP. Patients were defined as having LEP if their self-reported primary language was anything other than English and interpreter services were required during hospitalization. The primary outcome was inpatient mortality. Mortality was compared across races stratified by LEP using chi-squared tests of significance. Bivariable and multivariable logistic regressions were performed to investigate the association between mortality, race, and LEP, adjusting for baseline characteristics, comorbidities, and illness severity.

Results

Among 8,974 patients with sepsis, we found that 1 in 5 had LEP, 62% of whom were Asian. LEP was highly associated with death across all races except those identifying as Black and Latino. LEP was associated with a 31% increased odds of mortality after adjusting for illness severity, comorbidities, and other baseline characteristics, including race (OR 1.31, 95% CI 1.06-1.63, P = .02).

Conclusions

In a single-center study of patients hospitalized with sepsis, LEP was associated with mortality across nearly all races. This is a novel finding that will require further exploration into the causal nature of this association.