The natural history of symptoms and distress in patients and families following cystectomy for treatment of muscle invasive bladder cancer.

PURPOSE: We characterized the natural history of symptoms with time in patients with bladder cancer undergoing cystectomy. MATERIALS AND METHODS: For 6 months we followed 33 participants treated with muscle invasive bladder cancer treatment with cystectomy in this prospective cohort study. Patients and family caregivers completed validated symptom assessment and satisfaction surveys at baseline, and 2, 4 and 6 months later. Primary outcomes were the change from baseline in pain, fatigue, depression, anxiety, quality of life and spiritual well-being. Secondary outcomes included posttraumatic growth, patient satisfaction and family caregiver burden. RESULTS: Pain increased after radical cystectomy and remained increased 6 months postoperatively based on Brief Pain Inventory scores (baseline and 6-month scores 4.0, 95% CI 0-8.0 and 9.8, 95% CI 1.9-17.6, respectively, p = 0.03). Posttraumatic growth showed a trend toward an increase at 2 months (p = 0.06). Fatigue peaked at 4 months but did not change significantly with time (p = 0.12). There was similarly no significant change with time in depression, anxiety, quality of life, spiritual well-being or satisfaction. Neither family caregiver burden nor satisfaction showed a statistically significant change with time postoperatively. CONCLUSIONS: Pain increased after radical cystectomy and remained increased 6 months postoperatively. There was a trend toward increased posttraumatic growth at 2 months. Otherwise, by 6 months cystectomy was associated with no improvement in preoperative symptoms of fatigue, quality of life, spiritual well-being, depression or anxiety. After cystectomy pain should be assessed and treated more aggressively in patients with bladder cancer and efforts should be made to improve postoperative symptoms.

Optical Coherence Tomography Characteristics of the Choroid Underlying Congenital Hypertrophy of the Retinal Pigment Epithelium.

PURPOSE: This study evaluates and characterizes the choroid underlying congenital hypertrophy of the retinal pigment epithelium (CHRPE). METHODS: Retrospective observational study of CHRPE at least 2 mm in diameter. Choroidal vascular architecture was qualitatively examined. Choroidal thickness was measured by 2 independent observers using enhanced depth imaging spectral domain optical coherence tomography. RESULTS: Forty-six eyes of 46 patients with CHRPE were included. Thirty-two lesions had imaging sufficient for analysis. Haller's layer was healthy in 18 (56%), thin in 13 (41%), and absent in 1 (2%). Sattler's layer was atrophic in 30 (94%), and choriocapillaris was atrophic in 31 (97%). CHRPE with thinned Haller's layer had significantly larger diameter. The mean sub-CHRPE choroidal thickness was 82.4 ± 7.9 µm, compared to a thickness of 148.4 ± 9.6 µm in the normal adjacent choroid (p < 0.0001). Mean retinal thickness overlying the CHRPE was 77.3 ± 4.3 µm, compared to a retinal thickness of 137.8 ± 2.9 µm overlying the normal adjacent choroid (p < 0.0001). Sub-CHRPE choroidal thickness was a mean of 56.2 ± 3.1% of the adjacent normal choroidal thickness. CONCLUSION: The underlying choroid CHRPE is thinner than the adjacent normal choroid. All layers of the choroid can be thin with a preference of the inner Sattler's and choriocapillaris layers.

A Citizen Science and Government Collaboration: Developing Tools to Facilitate Community Air Monitoring.

The U.S. Environmental Protection Agency (EPA) is actively involved in supporting citizen science projects and providing communities with information and assistance for conducting their own air pollution monitoring. As part of a Regional Applied Research Effort (RARE) project, EPA's Office of Research and Development (ORD) worked collaboratively with EPA Region 2 and the Ironbound Community Corporation (ICC) in Newark, New Jersey, to develop and test the "Air Sensor Toolbox for Citizen Scientists." In this collaboration, citizen scientists measured local gaseous and particulate air pollution levels by using a customized low-cost sensor pod designed and fabricated by EPA. This citizen science air quality measurement project provided an excellent opportunity for EPA to evaluate and improve the Toolbox resources available to communities. The Air Sensor Toolbox, developed in coordination with the ICC, can serve as a template for communities across the country to use in developing their own air pollution monitoring programs in areas where air pollution is a concern. This pilot project provided an opportunity for a highly motivated citizen science organization and the EPA to work together directly to address environmental concerns within the community. Useful lessons were learned about how to improve coordination between the government and communities and the types of tools and technologies needed for conducting an effective citizen science project that can be applied to future efforts.

Misclassification of acute respiratory distress syndrome after traumatic injury: The cost of less rigorous approaches.

BACKGROUND: Adherence to rigorous research protocols for identifying adult respiratory distress syndrome (ARDS) after trauma is variable. To examine how misclassification of ARDS may bias observational studies in trauma populations, we evaluated the agreement of two methods for adjudicating ARDS after trauma: the current gold standard, direct review of chest radiographs and review of dictated radiology reports, a commonly used alternative. METHODS: This nested cohort study included 123 mechanically ventilated patients between 2005 and 2008, with at least one PaO2/FIO2 less than 300 within the first 8 days of admission. Two blinded physician investigators adjudicated ARDS by two methods. The investigators directly reviewed all chest radiographs to evaluate for bilateral infiltrates. Several months later, blinded to their previous assessments, they adjudicated ARDS using a standardized rubric to classify radiology reports. A κ statistics was calculated. Regression analyses quantified the association between established risk factors as well as important clinical outcomes and ARDS determined by the aforementioned methods as well as hypoxemia as a surrogate marker. RESULTS: The κ was 0.47 for the observed agreement between ARDS adjudicated by direct review of chest radiographs and ARDS adjudicated by review of radiology reports. Both the magnitude and direction of bias on the estimates of association between ARDS and established risk factors as well as clinical outcomes varied by method of adjudication. CONCLUSION: Classification of ARDS by review of dictated radiology reports had only moderate agreement with the current gold standard, ARDS adjudicated by direct review of chest radiographs. While the misclassification of ARDS had varied effects on the estimates of associations with established risk factors, it tended to weaken the association of ARDS with important clinical outcomes. A standardized approach to ARDS adjudication after trauma by direct review of chest radiographs will minimize misclassification bias in future observational studies. LEVEL OF EVIDENCE: Diagnostic study, level II.

Cause and timing of death in massively transfused trauma patients.

BACKGROUND: The purpose of this study was to characterize the cause of death in severely injured trauma patients to define potential responses to resuscitation. METHODS: Prospective analysis of 190 critically injured patients who underwent massive transfusion protocol (MTP) activation or received massive transfusion (>10 U of packed red blood cells [RBC] per 24 hours). Cause of death was adjudicated into one of four categories as follows: (1) exsanguination, (2) early physiologic collapse, (3) late physiologic collapse, and (4) nonsurvivable injury. RESULTS: A total 190 patients underwent massive transfusion or MTP with 76 deaths (40% mortality), of whom 72 deaths were adjudicated to one of four categories: 33.3% died of exsanguination, 16.6% died of early physiologic collapse, 11.1% died of late physiologic collapse, while 38.8% died of nonsurvivable injuries. Patients who died of exsanguination were younger and had the highest RBC/fresh frozen plasma ratio (2.97 [2.24]), although the early physiologic collapse group survived long enough to use the most blood products (p < 0.001). The late physiologic collapse group had significantly fewer penetrating injuries, was older, and had significantly more crystalloid use but received a lower RBC/fresh frozen plasma ratio (1.50 [0.42]). Those who were determined to have a nonsurvivable injury had a lower presenting Glasgow Coma Scale (GCS) score, fewer penetrating injuries, and higher initial blood pressure reflecting a preponderance of nonsurvivable traumatic brain injury. The average survival time for patients with potentially survivable injuries was 2.4 hours versus 18.4 hours for nonsurvivable injuries (p < 0.001). CONCLUSION: Severely injured patients requiring MTP have a high mortality rate. However, no studies to date have addressed the cause of death after MTP. Characterization of cause of death will allow targeting of surgical and resuscitative conduct to allow extension of the physiologic reserve time, therefore rendering previously nonsurvivable injury potentially survivable.

Characterization of platelet dysfunction after trauma.

BACKGROUND: The increased morbidity and mortality associated with coagulopathy and thrombocytopenia after trauma are well described. However, few studies have assessed platelet function after injury. METHODS: Blood samples were prospectively collected from 101 patients with critical injury and trauma on arrival to the emergency department and serially after admission to a Level I urban trauma intensive care unit from November 2010 to October 2011 and functionally assayed for responsiveness to adenosine diphosphate, thrombin receptor-activating peptide, arachidonic acid (AA), and collagen using multiple electrode impedance aggregometry. RESULTS: Of the 101 enrolled patients, 46 (45.5%) had below-normal platelet response to at least one agonist ("platelet hypofunction") at admission, and 92 patients (91.1%) had platelet hypofunction some time during their intensive care unit stay. Admission platelet hypofunction was associated with low Glasgow Coma Scale score and a nearly 10-fold higher early mortality. Logistic regression identified admission Glasgow Coma Scale (odds ratio, 0.819; p = 0.008) and base deficit (odds ratio, 0.872; p = 0.033) as independent predictors of platelet hypofunction. Admission AA and collagen responsiveness were significantly lower for patients who died (p < 0.01), whereas admission platelet counts were similar (p = 0.278); Cox regression confirmed thrombin receptor-activating peptide, AA, and collagen responsiveness as independent predictors of in-hospital mortality (p < 0.05). Receiver operating characteristic analysis identified admission AA and collagen responsiveness as negative predictors of both 24-hour (AA area under the curve [AUC], 0.874; collagen AUC, 0.904) and in-hospital mortality (AA AUC, 0.769; collagen AUC, 0.717). CONCLUSION: In this prognostic study, we identify clinically significant platelet dysfunction after trauma in the presence of an otherwise reassuring platelet count and standard clotting studies, with profound implications for mortality. Multiple electrode impedance aggregometry reliably identifies this dysfunction in injured patients, and admission AA and collagen responsiveness are sensitive and specific independent predictors of both early and late mortality.

Criteria for empiric treatment of hyperfibrinolysis after trauma.

BACKGROUND: Recent studies identify a survival benefit from the administration of antifibrinolytic agents in patients with severe injury and trauma. However, identification of hyperfibrinolysis requires thromboelastography, which is not widely available. We hypothesized that analysis of patients with thromboelastography-diagnosed hyperfibrinolysis would identify clinical criteria for empiric antifibrinolytic treatment in the absence of thromboelastography. METHODS: From November 2010 to March 2012, serial blood samples were collected from 115 patients with critical injury on arrival to the emergency department of an urban Level I trauma center. Rotational thromboelastography was performed to assess viscoelastic properties of clot formation in the presence and absence of aprotinin to identify treatable hyperfibrinolysis. For 20 patients identified with treatable hyperfibrinolysis, clinical predictors were investigated using receiver operating characteristic analysis. RESULTS: Of the 115 patients evaluated, 20% had hyperfibrinolysis, defined as an admission maximal clot lysis of 10% or higher, reversible by aprotinin treatment. Patients with hyperfibrinolysis had significantly lower temperature, pH, and platelet counts and higher international normalized ratio, activated partial thromboplastin time, and D-dimer. Hyperfibrinolysis was associated with multiorgan failure (63.2% vs. 24.6%, p = 0.004) and mortality (52.2% vs. 12.9%, p < 0.001). We then evaluated all non-rotational thromboelastography clinical and laboratory parameters predictive of hyperfibrinolysis using receiver operating characteristic analysis to evaluate potential empiric treatment guidelines. The presence of hypothermia (temperature ≤36.0°C), acidosis (pH ≤7.2), relative coagulopathy (international normalized ratio ≥1.3 or activated partial thromboplastin time ≥30), or relative thrombocytopenia (platelet count ≤200) identified hyperfibrinolysis with 100% sensitivity and 55.4% specificity (area under the curve, 0.777). CONCLUSION: Consideration of empiric antifibrinolytic therapy is warranted for patients with critical injury and trauma who present with acidosis, hypothermia, coagulopathy, or relative thrombocytopenia. These clinical predictors identified hyperfibrinolysis with 100% sensitivity while simultaneously eliminating 46.6% of inappropriate therapy compared with the empiric treatment of all injured patients. These criteria will facilitate empiric treatment of hyperfibrinolysis for clinicians without access to thromboelastography. LEVEL OF EVIDENCE: Prognostic study, level III.