Barriers to administering intravenous tissue plasminogen activator (tPA) for acute ischemic stroke in the emergency department: A cross-sectional survey of stroke centers.

OBJECTIVE: The logistics involved in administration of IV tPA for acute ischemic stroke patients are complex, and may contribute to variability in door-to-needle times between different hospitals. We sought to identify practice patterns in stroke centers related to IV tPA use. We hypothesized that there would be significant variability in logistics related to ancillary staff (i.e. nursing, pharmacists) processes in the emergency room setting. METHODS: A 21 question survey was distributed to attendees of the AHA/ASA Southwest Affiliate Stroke Coordinators Conference to evaluate potential barriers and delays with regards to thrombolysis for acute strokes patients in the Emergency Department setting. Answers were anonymous and aggregated to examine trends in responses. RESULTS: Responses were obtained from 37 of 67 (55%) stroke centers, which were located mainly in the Southwest United States. Logistical processes differed between facilities. Nursing and pharmacy carried stroke pagers in only 19% of the centers, and pharmacy responded to stroke alerts only one-third of centers. Insertion of Foley catheters and nasogastric tubes prior to tPA was routine in some of the sites. Other barriers to IV tPA administration included physician reluctance and inadequate communication between health care providers. CONCLUSION: Practices regarding logistics for giving IV tPA may be variable amongst different stroke centers. Given this potential variability, prospective evaluation to confirm these preliminary findings is warranted.

Immunodeficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections.

We developed an immunodeficiency scoring index for respiratory syncytial virus (ISI-RSV) infection, based on a cohort of 237 allogeneic hematopoietic cell transplant (allo-HCT) recipients, that can predict the risk of progression to lower respiratory tract infection (LRTI) and RSV-associated mortality. A weighted index was calculated using adjusted hazard ratios for immunodeficiency markers. Based on the ISI-RSV (range, 0-12), patients were stratified into low (0-2), moderate (3-6), and high (7-12) risk groups. A significant trend of increasing incidence of LRTI and RSV-associated mortality was observed as the risk increased from low to moderate to high (P < .001). Patients in the high-risk group had the greatest benefit of ribavirin-based therapy at the upper respiratory tract infection stage and the highest risk for progression to LRTI and death when antiviral therapy was not given (6.5 [95% confidence interval (CI), 1.8-23.6] and 8.1 [95% CI, 1.1-57.6], respectively). The ISI-RSV is designed to stratify allo-HCT recipients with RSV infection into groups according to their risk for progression to LRTI and RSV-associated mortality. Identification of high-risk groups using this index would distinguish patients who would benefit the most from antiviral therapy, mainly with aerosolized ribavirin. The ISI-RSV should be validated in a multi-institutional study.

Respiratory syncytial virus infections in children with cancer.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in children, especially those with cancer. Data on RSV infections in this vulnerable population is limited. We conducted a retrospective study of all RSV infections in children with cancer from 1998 to 2009 to determine characteristics and outcomes of these infections, identify risk factors for LRTI and mortality, and the effect of antiviral therapy on these outcomes. We identified 59 patients with a median age of 5 years; 53% had hematologic malignancy, 32% were hematopoietic stem cell transplant recipients, 39% had received corticosteroids, and 76% cytotoxic chemotherapy within 1 month before RSV infection. LRTI developed in 22 (37%) patients with a trend of higher rate in males (odds ratio=2.57 [0.86-7.62], P=0.09) and children with lymphocytopenia (odds ratio=2.95 [0.86-10.12], P=0.085). No significant differences were observed in the rates of progression to LRTI (3/10 [30%] vs. 19/49 [39%], P=0.729) and RSV-associated mortality (0/10 [0%] vs. 3/49 [6%], P=0.422) for patients receiving antiviral therapy at upper respiratory tract infection stage compared with those who did not. However, patients with LRTI had significantly better outcomes when treated with aerosolized ribavirin plus immunomodulators (mainly palivizumab) when compared with aerosolized ribavirin alone (mortality rates: 0/6 [0%] vs. 3/4 [75%], P=0.03). Ribavirin did not show any benefit in reducing LRTI or mortality; however, addition of palivizumab to the treatment regimen may be potentially beneficial, especially for children with LRTI.

Quantification of errors in ordinal outcome scales using shannon entropy: effect on sample size calculations.

OBJECTIVE: Clinical trial outcomes often involve an ordinal scale of subjective functional assessments but the optimal way to quantify results is not clear. In stroke, the most commonly used scale, the modified Rankin Score (mRS), a range of scores ("Shift") is proposed as superior to dichotomization because of greater information transfer. The influence of known uncertainties in mRS assessment has not been quantified. We hypothesized that errors caused by uncertainties could be quantified by applying information theory. Using Shannon's model, we quantified errors of the "Shift" compared to dichotomized outcomes using published distributions of mRS uncertainties and applied this model to clinical trials. METHODS: We identified 35 randomized stroke trials that met inclusion criteria. Each trial's mRS distribution was multiplied with the noise distribution from published mRS inter-rater variability to generate an error percentage for "shift" and dichotomized cut-points. For the SAINT I neuroprotectant trial, considered positive by "shift" mRS while the larger follow-up SAINT II trial was negative, we recalculated sample size required if classification uncertainty was taken into account. RESULTS: Considering the full mRS range, error rate was 26.1%±5.31 (Mean±SD). Error rates were lower for all dichotomizations tested using cut-points (e.g. mRS 1; 6.8%±2.89; overall p<0.001). Taking errors into account, SAINT I would have required 24% more subjects than were randomized. CONCLUSION: We show when uncertainty in assessments is considered, the lowest error rates are with dichotomization. While using the full range of mRS is conceptually appealing, a gain of information is counter-balanced by a decrease in reliability. The resultant errors need to be considered since sample size may otherwise be underestimated. In principle, we have outlined an approach to error estimation for any condition in which there are uncertainties in outcome assessment. We provide the user with programs to calculate and incorporate errors into sample size estimation.

Impact of aerosolized ribavirin on mortality in 280 allogeneic haematopoietic stem cell transplant recipients with respiratory syncytial virus infections.

OBJECTIVES: Respiratory syncytial virus (RSV) infections are well recognized as a significant cause of morbidity and mortality in allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients. We evaluated the spectrum of clinical manifestations, management (including ribavirin-based antiviral therapy) and outcomes of RSV infections and determined the risk factors associated with RSV lower respiratory tract infection (LRTI) and all-cause mortality. METHODS: In this retrospective study, we analysed clinical data from all laboratory-confirmed RSV infections in allo-HSCT recipients (n = 280) who presented at our institution from January 1996 to May 2009. RESULTS: Of the 280 patients, 80 (29%) developed LRTI within 20 days (median 1 day, range 0-19 days) and 44 (16%) died within 90 days (median 26 days, range 1-82 days) from RSV diagnosis. Multivariable logistic regression analyses identified several significant risk factors associated with RSV LRTI and all-cause mortality, including age, male sex, neutropenia, lymphocytopenia and lack of ribavirin-based antiviral therapy at the upper respiratory tract infection (URTI) stage. Aerosolized ribavirin-based therapy at the URTI stage was the single most significant factor in reducing the risk of RSV LRTI (83%), all-cause mortality (57%) and RSV-associated mortality (87%) in these patients (P < 0.05), irrespective of the year of RSV diagnosis. CONCLUSIONS: Our results demonstrate that RSV infections are a significant cause of morbidity and mortality in high-risk allo-HSCT recipients and ribavirin-based antiviral therapy at the URTI stage had a positive impact on both outcomes in this vulnerable population with multiple risk factors.

Characteristics and outcomes of methicillin-resistant staphylococcus aureus bloodstream infections in patients with cancer treated with vancomycin: 9-year experience at a comprehensive cancer center.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) can cause significant morbidity and mortality in patients with cancer. However, data on outcomes of patients treated with vancomycin are lacking. METHODS: We identified 223 patients with cancer who developed MRSA BSIs between January 2001 and June 2009 and were treated with vancomycin. Treatment failure was defined as death within 60 days of infection, persistent bacteremia ≥5 days, fever ≥4 days, recurrence or relapse, and secondary MRSA infection. RESULTS: The treatment failure rate was 52% (116 of 223 patients). These patients were more likely to have been hospitalized, been treated with steroids within the previous 3 months, developed acute respiratory distress syndrome, required mechanical ventilation, required intensive care unit care, and community-onset infections (all p < .05). Risk factors for MRSA-associated mortality (27 of 223 patients; 12%) included hematologic malignancy and hematopoietic stem cell transplantation, community-onset infection, secondary BSI, MRSA with minimum inhibitory concentration (MIC) ≥2.0 µg/mL, mechanical ventilation, and a late switch to an alternative therapy (≥4 days after treatment failure; all p < .05). On multivariate analysis, mechanical ventilation and recent hospitalization were identified as independent predictors of vancomycin failure, and community-onset infection, secondary BSIs, and MIC ≥2 µg/mL were identified as significant predictors of MRSA-associated mortality. CONCLUSIONS: We found a high treatment failure rate for vancomycin in patients with cancer and MRSA BSIs, as well as a higher mortality. A vancomycin MIC ≥2 µg/mL was an independent predictor of MRSA-associated mortality. An early switch to an alternative therapy at the earliest sign of failure may improve outcome.

Characteristics and outcomes of pandemic 2009/H1N1 versus seasonal influenza in children with cancer.

BACKGROUND: Novel 2009/H1N1 influenza has significant impact on immunocompromised children with cancer; however, it is uncertain how it compares with seasonal influenza (SFlu) in this vulnerable population. We compared clinical characteristics and outcomes for these 2 infections in children with cancer and identified risk factors for progression to lower respiratory infection (LRI) and/or death. METHODS: Influenza infections confirmed by positive viral culture and/or fluorescence antigen test between January 1998 and February 2010 were identified from microbiology databases at a comprehensive cancer center. Characteristics and outcomes were compared for the 2 groups. Kaplan-Meier survival curves and Cox proportional hazards model were generated to identify risk factors for LRI and/or death. RESULTS: When compared with SFlu, 2009/H1N1 cases had significantly lower acute physiology and chronic health evaluation II score (median: 9 versus 14), fewer comorbidities (15% versus 46%), fewer hematopoietic stem-cell transplantation (5% versus 16%), more solid tumors (45% versus 16%), higher LRI at presentation (20% versus 4%), higher rates of antiviral therapy (90% versus 48%) and higher mortality (10% versus 0%). Male gender (hazard ratio [HR]: 8.4, 95% confidence interval [CI]: 1.08-65.2, P = 0.042), acute physiology and chronic health evaluation II score > 15 (HR: 3.29, 95% CI: 1.04-10.39, P = 0.027) and a 24-hour delay in initiation of antiviral treatment (HR: 1.12, 95% CI: 1.02-1.23, P = 0.015) were the most significant predictors of progression to LRI and mortality, regardless of virus strain. CONCLUSIONS: Significant differences between 2009/H1N1 and SFlu with respect to clinical presentation, management and associated outcomes were identified. Early diagnosis and prompt initiation of antiviral therapy may prevent serious complications of influenza in children with cancer.

Is there evidence for late cognitive decline in chronic schizophrenia?

Schizophrenia (SZP) has been historically referred to as "dementia praecox" because of the recognition that its onset is associated with deficits in memory, attention and visuospatial orientation. We wondered whether there is evidence for additional cognitive decline late in the course of chronic SZP. This review examined the evidence (1) for cognitive decline late in the course of chronic SZP, (2) for how often the late cognitive decline occurs, and (3) whether the cognitive decline in late-life SZP is related to pathophysiology of SZP versus the superimposition of another type of dementia. A PUBMED search was performed combining the MESH terms schizophrenia and dementia, cognitive decline, cognitive impairment and cognitive deficits. A manual search of article bibliographies was also performed. We included longitudinal clinical studies employing standard tests of cognition. Cross-sectional studies and those that did not test cognition through standard cognitive tests were excluded. The initial search produced 3898 studies. Employing selection criteria yielded twenty-three studies. Our data extraction tool included the number of patients in the study, whether a control group was present, the age of patients at baseline and follow-up, the study setting (inpatients versus outpatients), the cognitive tests employed, study duration, and results. Only three longitudinal studies tested for dementia using Diagnostic and statistical manual of mental disorder (DSM) or International classification of disease (ICD) criteria and compared them to controls: two studies demonstrated an increase in the prevalence of dementia and one did not. Twenty longitudinal studies tested for one or more cognitive domains without employing standard criteria for dementia: twelve studies demonstrated a heterogeneous pattern of cognitive decline and eight did not. Studies generally did not control for known risk factors for cognitive impairment such as education, vascular risk factors, apolipoprotein (ApoE) genotype and family history. The evidence for late cognitive decline in SZP is mixed, but, slightly more studies suggest that it occurs. If it occurs, it is unclear whether it is related to SZP or other risks for cognitive impairment. Hence, prospective, longitudinal, controlled studies are needed to confirm that there is progressive cognitive decline in chronic SZP which occurs independent of other risk factors for cognitive impairment.

Management of RSV infections in adult recipients of hematopoietic stem cell transplantation.

Respiratory syncytial virus (RSV) is a common cause of seasonal respiratory viral infection in patients who have undergone hematopoietic stem cell transplantation. RSV usually presents as an upper respiratory tract infection in this patient population but may progress rapidly to lower respiratory tract infection. Available therapies that have been used for the treatment of RSV infections are limited to ribavirin, intravenous immunoglobulin, and palivizumab. The use of aerosolized ribavirin, alone or in combination with either palivizumab or intravenous immunoglobulin, remains controversial. In this comprehensive review, we present and discuss the available literature on management of RSV infections in adult hematopoietic stem cell transplantation recipients with a focus on therapeutic modalities and outcomes.

Characteristics and outcomes of methicillin-resistant Staphylococcus aureus surgical-site infections in patients with cancer: a case-control study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant cause of morbidity and mortality. We experienced an increased incidence of MRSA surgical-site infections (MRSA SSIs) at our institution. However, to our knowledge, no studies have evaluated the risk factors and outcomes of MRSA SSIs in cancer patients. METHODS: We conducted a case-control study and identified all patients who had developed MRSA SSIs at our institution from July 1, 2002 to July 30, 2003, and all patients who had undergone surgery by the same surgical team during the same time period but who had not developed MRSA SSIs. Cases and controls were age-matched at 1:2 ratio. RESULTS: The study included 29 cases and 58 controls. Mean interval between surgery and MRSA SSI onset was 17.8 days (range 3-75 days). Cases were more likely than controls to have progressive cancer (72 versus 38%), have received antibiotics (mainly quinolones) within 24 h of surgery (17 versus 2%), have had ongoing infection (10 versus 0%), and have had longer hospital and intensive care unit stays (11.0 versus 7.8 days and 3.4 versus 1.5 days) (all P < 0.05). In a multivariate logistic regression analysis, significant predictors of MRSA SSI in cancer patients were antibiotics use <24 h of surgery and progressive cancer. No surgical factors (i.e., procedure time or timing of perioperative antibiotics) were associated with increased risk of MRSA SSI. CONCLUSIONS: Several clinical and postoperative factors were associated with increased risk of MRSA SSI in cancer patients, but antibiotic use before surgery (especially quinolones) and progressive cancer were the only independent predictors.