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Chronic end-organ complications result in morbidity and mortality in adults with sickle cell disease (SCD). In a retrospective-prospective cohort of 150 adults with SCD who received standard care screening for pulmonary function abnormalities, cardiac disease, and renal assessment from January 2003 to 2016, we tested the hypothesis that clustering of end-organ disease is common and multiple organ impairment predicts mortality. Any end-organ disease occurred in 59.3% of individuals, and 24.0% developed multiple organ (>1) end-organ disease. The number of end-organs affected was associated with mortality (P ≤ .001); 8.2% (5 of 61) of individuals with no affected end-organ, 9.4% (5 of 53) of those with 1 affected organ, 20.7% (6 of 29) of those with 2 affected end-organs, and 85.7% (6 of 7) with 3 affected end-organs died over a median follow up period of 8.7 (interquartile range 3.5-11.4) years. Of the 22 individuals who died, 77.3% had evidence of any SCD-related end-organ impairment, and this was the primary or secondary cause of death in 45.0%. SCD-related chronic impairment in multiple organs, and its association with mortality, highlights the need to understand the common mechanisms underlying chronic end-organ damage in SCD, and the urgent need to develop interventions to prevent irreversible end-organ complications in SCD.
© 2018 Wiley Periodicals, Inc.
BACKGROUND - Adults hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality. However, it is unclear whether improvements in in-hospital pneumonia care could substantially lower this risk. We extensively reviewed all in-hospital deaths in a large prospective CAP study to assess the cause of each death and assess the extent of potentially preventable mortality.
METHODS - We enrolled adults hospitalized with CAP at five tertiary-care hospitals in the United States. Five physician investigators reviewed the medical record and study database for each patient who died to identify the cause of death, the contribution of CAP to death, and any preventable factors potentially contributing to death.
RESULTS - Among 2,320 enrolled patients, 52 (2.2%) died during initial hospitalization. Among these 52 patients, 33 (63.4%) were ≥ 65 years old, and 32 (61.5%) had ≥ two chronic comorbidities. CAP was judged to be the direct cause of death in 27 patients (51.9%). Ten patients (19.2%) had do-not-resuscitate orders prior to admission. Four patients were identified in whom a lapse in quality of care potentially contributed to death; preexisting end-of-life limitations were present in two of these patients. Two patients seeking full medical care experienced a lapse in in-hospital quality of pneumonia care that potentially contributed to death.
CONCLUSIONS - In this study of adults with CAP at tertiary-care hospitals with a low mortality rate, most in-hospital deaths did not appear to be preventable with improvements in in-hospital pneumonia care. Preexisting end-of-life limitations in care, advanced age, and high comorbidity burden were common among those who died.
Copyright © 2018 American College of Chest Physicians. All rights reserved.
INTRODUCTION - Hospital readmissions within 30 days are a healthcare quality problem associated with increased costs and poor health outcomes. Identifying interventions to improve patients' successful transition from inpatient to outpatient care is a continued challenge.
METHODS AND ANALYSIS - This is a single-centre pragmatic randomised and controlled clinical trial examining the effectiveness of a discharge follow-up phone call to reduce 30-day inpatient readmissions. Our primary endpoint is inpatient readmission within 30 days of hospital discharge censored for death analysed with an intention-to-treat approach. Secondary endpoints included observation status readmission within 30 days, time to readmission, all-cause emergency department revisits within 30 days, patient satisfaction (measured as mean Hospital Consumer Assessment of Healthcare Providers and Systems scores) and 30-day mortality. Exploratory endpoints include the need for assistance with discharge plan implementation among those randomised to the intervention arm and reached by the study nurse, and the number of call attempts to achieve successful intervention delivery. Consistent with the Learning Healthcare System model for clinical research, timeliness is a critical quality for studies to most effectively inform hospital clinical practice. We are challenged to apply pragmatic design elements in order to maintain a high-quality practicable study providing timely results. This type of prospective pragmatic trial empowers the advancement of hospital-wide evidence-based practice directly affecting patients.
ETHICS AND DISSEMINATION - Study results will inform the structure, objective and function of future iterations of the hospital's discharge follow-up phone call programme and be submitted for publication in the literature.
TRIAL REGISTRATION NUMBER - NCT03050918; Pre-results.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Importance - Pulmonary hypertension (PH) is diagnosed by a mean pulmonary arterial pressure (mPAP) value of at least 25 mm Hg during right heart catheterization (RHC). While several studies have demonstrated increased mortality in patients with mPAP less than that threshold, little is known about the natural history of borderline PH.
Objective - To test the hypothesis that patients with borderline PH have decreased survival compared with patients with lower mPAP and frequently develop overt PH and to identify clinical correlates of borderline PH.
Design, Setting, and Participants - Retrospective cohort study from 1998 to 2014 at Vanderbilt University Medical Center, comprising all patients undergoing routine RHC for clinical indication. We extracted demographics, clinical data, invasive hemodynamics, echocardiography, and vital status for all patients. Patients with mPAP values of 18 mm Hg or less, 19 to 24 mm Hg, and at least 25 mm Hg were classified as reference, borderline PH, and PH, respectively.
Exposures - Mean pulmonary arterial pressure.
Main Outcome and Measures - Our primary outcome was all-cause mortality after adjusting for clinically relevant covariates in a Cox proportional hazards model. Our secondary outcome was the diagnosis of overt PH in patients initially diagnosed with borderline PH. Both outcomes were determined prior to data analysis.
Results - We identified 4343 patients (mean [SD] age, 59  years, 51% women, and 86% white) among whom the prevalence of PH and borderline PH was 62% and 18%, respectively. Advanced age, features of the metabolic syndrome, and chronic heart and lung disease were independently associated with a higher likelihood of borderline PH compared with reference patients in a logistic regression model. After adjusting for 34 covariates in a Cox proportional hazards model, borderline PH was associated with increased mortality compared with reference patients (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = .001). The hazard of death increased incrementally with higher mPAP, without an observed threshold. In the 70 patients with borderline PH who underwent a repeated RHC, 43 (61%) had developed overt PH, with a median increase in mPAP of 5 mm Hg (interquartile range, -1 to 11 mm Hg; P < .001).
Conclusions and Relevance - Borderline PH is common in patients undergoing RHC and is associated with significant comorbidities, progression to overt PH, and decreased survival. Small increases in mPAP, even at values currently considered normal, are independently associated with increased mortality. Prospective studies are warranted to determine whether early intervention or closer monitoring improves clinical outcomes in these patients.
BACKGROUND - Critically ill patients with acute kidney injury (AKI) can be divided into two subphenotypes, resolving or nonresolving, on the basis of the trajectory of serum creatinine. It is unknown if the biology underlying these two AKI recovery patterns is different.
METHODS - We measured eight circulating biomarkers in plasma obtained from a cohort of patients admitted to an intensive care unit (ICU) (n = 1241) with systemic inflammatory response syndrome. The biomarkers were representative of several biologic processes: apoptosis (soluble Fas), inflammation (soluble tumor necrosis factor receptor 1, interleukin 6, interleukin 8) and endothelial dysfunction, (angiopoietin 1, angiopoietin 2, and soluble vascular cell adhesion molecule 1). We tested for associations between biomarker levels and AKI subphenotypes using relative risk regression accounting for multiple hypotheses with the Bonferroni correction.
RESULTS - During the first 3 days of ICU admission, 868 (70%) subjects developed AKI; 502 (40%) had a resolving subphenotype, and 366 (29%) had a nonresolving subphenotype. Hospital mortality was 12% in the resolving subphenotype and 21% in the nonresolving subphenotype. Soluble Fas was the only biomarker associated with a nonresolving subphenotype after adjustment for age, body mass index, diabetes, and Acute Physiology and Chronic Health Evaluation III score (p = 0.005).
CONCLUSIONS - Identifying modifiable targets in the Fas-mediated pathway may lead to strategies for prevention and treatment of a clinically important form of AKI.
BACKGROUND - The clinical significance of pneumonia visualized on CT scan in the setting of a normal chest radiograph is uncertain.
METHODS - In a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia (CAP), we compared the presenting clinical features, pathogens present, and outcomes of patients with pneumonia visualized on a CT scan but not on a concurrent chest radiograph (CT-only pneumonia) and those with pneumonia visualized on a chest radiograph. All patients underwent chest radiography; the decision to obtain CT imaging was determined by the treating clinicians. Chest radiographs and CT images were interpreted by study-dedicated thoracic radiologists blinded to the clinical data.
RESULTS - The study population included 2,251 adults with CAP; 2,185 patients (97%) had pneumonia visualized on chest radiography, whereas 66 patients (3%) had pneumonia visualized on CT scan but not on concurrent chest radiography. Overall, these patients with CT-only pneumonia had a clinical profile similar to those with pneumonia visualized on chest radiography, including comorbidities, vital signs, hospital length of stay, prevalence of viral (30% vs 26%) and bacterial (12% vs 14%) pathogens, ICU admission (23% vs 21%), use of mechanical ventilation (6% vs 5%), septic shock (5% vs 4%), and inhospital mortality (0 vs 2%).
CONCLUSIONS - Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography.
Copyright © 2017 American College of Chest Physicians. All rights reserved.
OBJECTIVE - To determine if beta-(β)-blockers improve outcomes after acute traumatic brain injury (TBI).
BACKGROUND - There have been no new inpatient pharmacologic therapies to improve TBI outcomes in a half-century. Treatment of TBI patients with β-blockers offers a potentially beneficial approach.
METHODS - Using MEDLINE, EMBASE, and CENTRAL databases, eligible articles for our systematic review and meta-analysis (PROSPERO CRD42016048547) included adult (age ≥ 16 years) blunt trauma patients admitted with TBI. The exposure of interest was β-blocker administration initiated during the hospitalization. Outcomes were mortality, functional measures, quality of life, cardiopulmonary morbidity (e.g., hypotension, bradycardia, bronchospasm, and/or congestive heart failure). Data were analyzed using a random-effects model, and represented by pooled odds ratio (OR) with 95% confidence intervals (CI) and statistical heterogeneity (I).
RESULTS - Data were extracted from 9 included studies encompassing 2005 unique TBI patients with β-blocker treatment and 6240 unique controls. Exposure to β-blockers after TBI was associated with a reduction of in-hospital mortality (pooled OR 0.39, 95% CI: 0.27-0.56; I = 65%, P < 0.00001). None of the included studies examined functional outcome or quality of life measures, and cardiopulmonary adverse events were rarely reported. No clear evidence of reporting bias was identified.
CONCLUSIONS - In adults with acute TBI, observational studies reveal a significant mortality advantage with β-blockers; however, quality of evidence is very low. We conditionally recommend the use of in-hospital β-blockers. However, we recommend further high-quality trials to answer questions about the mechanisms of action, effectiveness on subgroups, dose-response, length of therapy, functional outcome, and quality of life after β-blocker use for TBI.
Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low-resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low-resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric-hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The pre-intervention period was assessed through a retrospective chart review to identify every death and the post-intervention period was assessed prospectively. Interventions consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre- and post- intervention periods, respectively. The maternal mortality rate decreased from 10 791 per 100 000 live births at pre-intervention to 1176 per 100 000 at post-intervention, representing a risk reduction of 89.1% (P = 0.007). Perinatal mortality decreased from 60.8 per 1000 total births at pre-intervention to 23.0 per 1000 at post-intervention, representing a risk reduction of 62.2% (P = 0.20). A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low-resource setting.
© 2017 Wiley Periodicals, Inc.
STUDY OBJECTIVE - Induction doses of etomidate during rapid sequence intubation cause transient adrenal dysfunction, but its clinical significance on trauma patients is uncertain. Ketamine has emerged as an alternative for rapid sequence intubation induction. Among adult trauma patients intubated in the emergency department, we compare clinical outcomes among those induced with etomidate and ketamine.
METHODS - The study entailed a retrospective evaluation of a 4-year (January 2011 to December 2014) period spanning an institutional protocol switch from etomidate to ketamine as the standard induction agent for adult trauma patients undergoing rapid sequence intubation in the emergency department of an academic Level I trauma center. The primary outcome was hospital mortality evaluated with multivariable logistic regression, adjusted for age, vital signs, and injury severity and mechanism. Secondary outcomes included ICU-free days and ventilator-free days evaluated with multivariable ordered logistic regression using the same covariates.
RESULTS - The analysis included 968 patients, including 526 with etomidate and 442 with ketamine. Hospital mortality was 20.4% among patients induced with ketamine compared with 17.3% among those induced with etomidate (adjusted odds ratio [OR] 1.41; 95% confidence interval [CI] 0.92 to 2.16). Patients induced with ketamine had ICU-free days (adjusted OR 0.80; 95% CI 0.63 to 1.00) and ventilator-free days (adjusted OR 0.96; 95% CI 0.76 to 1.20) similar to those of patients induced with etomidate.
CONCLUSION - In this analysis spanning an institutional protocol switch from etomidate to ketamine as the standard rapid sequence intubation induction agent for adult trauma patients, patient-centered outcomes were similar for patients who received etomidate and ketamine.
Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
BACKGROUND - Large social networks have been associated with better overall survival, though not consistently with breast cancer (BC)-specific outcomes. This study evaluated associations of postdiagnosis social networks and BC outcomes in a large cohort.
METHODS - Women from the After Breast Cancer Pooling Project (n = 9267) provided data on social networks within approximately 2 years of their diagnosis. A social network index was derived from information about the presence of a spouse/partner, religious ties, community ties, friendship ties, and numbers of living first-degree relatives. Cox models were used to evaluate associations, and a meta-analysis was used to determine whether effect estimates differed by cohort. Stratification by demographic, social, tumor, and treatment factors was performed.
RESULTS - There were 1448 recurrences and 1521 deaths (990 due to BC). Associations were similar in 3 of 4 cohorts. After covariate adjustments, socially isolated women (small networks) had higher risks of recurrence (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.15-1.77), BC-specific mortality (HR, 1.64; 95% CI, 1.33-2.03), and total mortality (HR, 1.69; 95% CI, 1.43-1.99) than socially integrated women; associations were stronger in those with stage I/II cancer. In the fourth cohort, there were no significant associations with BC-specific outcomes. A lack of a spouse/partner (P = .02) and community ties (P = .04) predicted higher BC-specific mortality in older white women but not in other women. However, a lack of relatives (P = .02) and friendship ties (P = .01) predicted higher BC-specific mortality in nonwhite women only.
CONCLUSIONS - In a large pooled cohort, larger social networks were associated with better BC-specific and overall survival. Clinicians should assess social network information as a marker of prognosis because critical supports may differ with sociodemographic factors. Cancer 2017;123:1228-1237. © 2016 American Cancer Society.
© 2016 American Cancer Society.