Sociodemographic Disparities in Postoperative Nausea and Vomiting.

BACKGROUND: Postoperative nausea and vomiting (PONV) prophylaxis is consistently considered a key indicator of anesthesia care quality. PONV may disproportionately impact disadvantaged patients. The primary objectives of this study were to examine the associations between sociodemographic factors and the incidence of PONV and clinician adherence to a PONV prophylaxis protocol. METHODS: We conducted a retrospective analysis of all patients eligible for an institution-specific PONV prophylaxis protocol (2015-2017). Sociodemographic and PONV risk data were collected. Primary outcomes were PONV incidence and clinician adherence to PONV prophylaxis protocol. We used descriptive statistics to compare sociodemographics, procedural characteristics, and protocol adherence for patients with and without PONV. Multivariable logistic regression analysis followed by Tukey-Kramer correction for multiple comparisons was used to test for associations between patient sociodemographics, procedural characteristics, PONV risk, and (1) PONV incidence and (2) adherence to PONV prophylaxis protocol. RESULTS: Within the 8384 patient sample, Black patients had a 17% lower risk of PONV than White patients (adjusted odds ratio [aOR], 0.83; 95% confidence interval [CI], 0.73-0.95; P = .006). When there was adherence to the PONV prophylaxis protocol, Black patients were less likely to experience PONV compared to White patients (aOR, 0.81; 95% CI, 0.70-0.93; P = .003). When there was adherence to the protocol, patients with Medicaid were less likely to experience PONV compared to privately insured patients (aOR, 0.72; 95% CI, 0.64-1.04; P = .017). When the protocol was followed for high-risk patients, Hispanic patients were more likely to experience PONV than White patients (aOR, 2.96; 95% CI, 1.18-7.42; adjusted P = .022). Compared to White patients, protocol adherence was lower for Black patients with moderate (aOR, 0.76; 95% CI, 0.64-0.91; P = .003) and high risk (aOR, 0.57; 95% CI, 0.42-0.78; P = .0004). CONCLUSIONS: Racial and sociodemographic disparities exist in the incidence of PONV and clinician adherence to a PONV prophylaxis protocol. Awareness of such disparities in PONV prophylaxis could improve the quality of perioperative care.

Improving Adherence to Intraoperative Lung-Protective Ventilation Strategies Using Near Real-Time Feedback and Individualized Electronic Reporting.

BACKGROUND: Postoperative pulmonary complications can have a significant impact on the morbidity and mortality of patients undergoing major surgeries. Intraoperative lung protective strategies using low tidal volume (TV) ventilation and positive end-expiratory pressure (PEEP) have been demonstrated to reduce the incidence of pulmonary injury and infection while improving oxygenation and respiratory mechanics. The purpose of this study was to develop decision support systems designed to optimize behavior of the attending anesthesiologist with regards to adherence with established intraoperative lung-protective ventilation (LPV) strategies. METHODS: Over a 4-year period, data were obtained from 49,386 procedures and 109 attendings. Cases were restricted to patients aged 18 years or older requiring general anesthesia that lasted at least 60 minutes. We defined protective lung ventilation as a TV of 6-8 mL/kg ideal body weight and a PEEP of ≥4 cm H2O. There was a baseline period followed by 4 behavioral interventions: education, near real-time feedback, individualized post hoc feedback, and enhanced multidimensional decision support. Segmented logistic regression using generalized estimating equations was performed in order to assess temporal trends and effects of interventions on adherence to LPV strategies. RESULTS: Consistent with improvement in adherence with LPV strategies during the baseline period, the predicted probability of adherence with LPV at the end of baseline was 0.452 (95% confidence interval [CI], 0.422-0.483). The improvements observed for each phase were relative to the preceding phase. Education alone was associated with an 8.7% improvement (P < .01) in adherence to lung-protective protocols and was associated with a 16% increase in odds of adherence (odds ratio [OR] = 1.16; 95% CI, 1.01-1.33; P = .04). Near real-time, on-screen feedback was associated with an estimated 15.5% improvement in adherence (P < .01) with a 69% increase in odds of adherence (OR = 1.69; 95% CI, 1.46-1.96; P < .01) over education alone. The addition of an individualized dashboard with personal adherence and peer comparison was associated with a significant improvement over near real-time feedback (P < .01). Near real-time feedback and dashboard feedback systems were enhanced based on feedback from the in-room attendings, and this combination was associated with an 18.1% (P < .01) increase in adherence with a 2-fold increase in the odds of adherence (OR = 2.23; 95% CI, 1.85-2.69; P < .0001) between the end of the previous on-screen feedback phase and the start of the individualized post hoc dashboard reporting phase. The adherence with lung-protective strategies using the multidimensional approach has been sustained for over 24 months. The difference between the end of the previous phase and the start of this last enhanced multidimensional decision support phase was not significant (OR = 1.08; 95% CI, 0.86-1.34; P = .48). CONCLUSIONS: Consistent with the literature, near real-time and post hoc reporting are associated with positive and sustained behavioral changes aimed at adopting evidence-based clinical strategies. Many decision support systems have demonstrated impact to behavior, but the effect is often transient. The implementation of near real-time feedback and individualized post hoc decision support tools has resulted in clinically relevant improvements in adherence with LPV strategies that have been sustained for over 24 months, a common limitation of decision support solutions.

Evaluation of the exposure prediction component of Control of Substances Hazardous to Health Essentials.

The exposure prediction component of the Control of Substances Hazardous to Health (COSHH) Essentials model (paper version) was evaluated using field measurements from National Institute of Occupational Safety and Health (NIOSH) Health Hazard Evaluation (HHE) reports. Overall 757 measured exposures for 94 similar exposure groups (SEGs) were compared with the COSHH Essentials predicted exposure range (PER). The SEGs were stratified based on the magnitude of measured exposures (high, medium, or low) and physical state of the substance (vapor or particulate). The majority of measured exposures observed involved low-level exposure to vapors; thus, overall findings from the current study are limited to low-level vapor exposure scenarios. Overall, the exposure prediction component of COSHH Essentials vastly overestimated low-level exposures to vapors. This study went beyond the scope of previous studies and investigated which model components led to the overestimation. It was concluded that COSHH Essential's tendency to overestimate was due to multiple complex interactions among model components. Overall, the magnitude of overestimation seems to increase exponentially as values for predictor variables increase. This is likely due to the log-based scale used by the model to allocate concentration ranges. In addition, the current banding scheme used to allocate volatility appears to play a role in the overestimation of low-level exposures to vapors.

Stroke Center Certification and Performance: A Longitudinal Analysis of the Northeast Cerebrovascular Consortium Region.

Background: The NorthEast Cerebrovascular Consortium (NECC) was established in 2006 to improve stroke-systems-of-care models. Methods: This study evaluates the increase in stroke quality over time in NECC and Non-NECC regions, defined as the change in proportion of hospitals over time who received State or National Primary/Comprehensive Stroke Center (PSC/CSC) certification, participated in a national quality program (Get-With-The-Guidelines-Stroke (GWTG-S)), or received GWTG-S Performance Achievement Awards (PAA) from 2005-2013. Analysis of trends was performed (Cochran-Armitage/Cochran-Mantel-Haenszel tests; Generalized-Estimating Equations). As an exploratory analysis eight NECC region Departments of Health (DOH) were surveyed regarding perceptions of the NECC. Results: During the study period, there were 433.1 ± 10.2 vs 3986.4 ± 187.7 hospitals per year in the NECC vs non-NECC regions. Rate of growth per year increased in both groups for each measure but to a greater degree in the NECC vs Non-NECC regions: PSC/CSC (5.4%/yr vs 3.2%/yr), GWTG-S participation (5.0%/yr vs 2.9%/yr), and PAAs (5.2%/yr vs 2.1%/yr), with state-based certification growth also being higher in the NECC region (4.2%/yr vs 0.4%/yr; all comparisons p < 0.0001). After adjusting for year, significantly more NECC hospitals had PSC/CSC certification, GWTG-S participation, and GWTG-S PAAs than non-NECC sites (all analyses p < 0.0001). One hundred percent of NECC region DOHs were aware of the NECC and involved in functions, 87.5% indicated the NECC provided beneficial assistance. Conclusions: There has been a higher rate of growth of state certification contrasted to national PSC/CSC certification, and a higher rate of growth of participation and achievement in GWTG-S in the northeast region compared to other US regions.

Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study.

Calorie restriction (CR), a reduction of 10­40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7­14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.

Race influences warfarin dose changes associated with genetic factors.

Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study and compared predictive ability of race-combined vs race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, and CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and by rs12777823 in African Americans. CYP2C9*2 was associated with a lower dose only among European Americans (20.6% vs 3.0%, P < .001) and rs12777823 only among African Americans (12.3% vs 2.3%, P = .006). Although VKORC1 was associated with dose decrease in both races, the proportional decrease was higher among European Americans (28.9% vs 19.9%, P = .003) compared with African Americans. Race-stratified analysis improved dose prediction in both race groups compared with race-combined analysis. We demonstrate that the effect of predictors on warfarin dose differs by race, which may explain divergent findings reported by recent warfarin pharmacogenetic trials. We recommend that warfarin dosing algorithms should be stratified by race rather than adjusted for race.

Psychometric evaluation of an online and paper accidental bowel leakage questionnaire: The ICIQ-B questionnaire.

AIMS: To evaluate the psychometric properties of an online versus paper US-English version of the International Consultation on Incontinence Questionnaire-Bowel (ICIQ-B). METHODS: The ICIQ-B includes 17 items under 3 domains: bowel pattern (5 items), bowel control (7 items), and quality of life (5 items). We recruited community-dwelling adults seeking treatment for ≥monthly bowel leakage from specialty clinics within a VA medical center and university affiliate. An online versus paper version was evaluated at baseline, 2 weeks later, and 3 months after nonsurgical treatments per usual care. We assessed test-retest reliability (Pearson correlations) at 2 weeks, internal consistency (Cronbach's alpha), and convergent validity (Pearson correlations). Sensitivity to change was the difference between the baseline and post-treatment (3-month) scores. RESULTS: Mean age was 58.0 ± 11.9; 36% Veterans, 52% women. At baseline, 2 weeks, and 3 months, we found no differences in the online vs paper scores for the bowel control and quality of life domains. The ICIQ-B demonstrated fair internal consistency for the bowel pattern domain (Cronbach's α = 0.36-0.54). Internal consistency on the bowel pattern domain was better with the paper version than the online version at 2 weeks (P < 0.05) and 3 months (P < 0.01) with no difference at baseline. All other domains had good internal consistency (Cronbach's α > 0.80), good retest reliability (r ≥ 0.70, P < 0.001), domain-specific convergent validity for stool consistency (P < 0.05), incontinence severity (P ≤ 0.002), and quality of life impact (P < 0.05). After nonsurgical treatments, we found a reasonable response to change (P ≤ 0.05). CONCLUSIONS: Online and paper versions had robust psychometric data for use among U.S. men and women, including Veterans. Neurourol. Urodynam. 36:166-170, 2017. © 2015 Wiley Periodicals, Inc.

Addressing Stroke Risk Factors in Black and White Americans: Findings from the National Health and Nutrition Examination Survey, 2009-2010.

OBJECTIVE: Recurrent stroke affects 5%-15% of stroke survivors, is higher among Blacks, and preventable with secondary stroke prevention medications. Our study aimed to examine racial differences in risk factors being addressed (defined as either on active treatment or within guideline levels) among stroke survivors and those at risk for stroke. METHODS: A cross-sectional study using NHANES 2009-2010 standardized interviews of Whites and Blacks aged ≥18 years. Risk factors were defined as being addressed if: 1) for hypertension, SBP <140, DBP <90 (SBP<130, DBP<80 for diabetics) or using BP-lowering medications; 2) for current smoking, using cessation medications; and 3) for hyperlipidemia, LDL<100 (LDL<70 for stroke survivors) or using lipid-lowering medications. Participants were stratified by stroke history. Prevalence of addressed risk factors was compared by race. RESULTS: Among 4005 participants (mean age 48, 52% women, 15% Black), 4% reported a history of stroke. Among stroke survivors, there were no statistically significant differences in Blacks and Whites having their hypertension or hyperlipidemia addressed. Among stroke naïve participants, the prevalence of addressed hypertension (P<.01) and hyperlipidemia (P<.01) was lower in Blacks compared with Whites. CONCLUSIONS: We found that addressed hypertension and hyperlipidemia in stroke naïve participants were significantly lower in Blacks than Whites. Our observations call attention to areas that require further investigation, such as why Black Americans may not be receiving evidence-based pharmacologic therapy for hypertension and hyperlipidemia or why Black Americans are not at goal blood pressure or goal LDL. A better understanding of this information is critical to preventing stroke and other vascular diseases.

Influence of kidney function on risk of supratherapeutic international normalized ratio-related hemorrhage in warfarin users: a prospective cohort study.

BACKGROUND: Anticoagulation management is difficult in chronic kidney disease, with frequent supratherapeutic international normalized ratios (INRs ≥ 4) increasing hemorrhagic risk. We evaluated whether the interaction of INR and lower estimated glomerular filtration rate (eGFR) increases hemorrhage risk and whether patients with lower eGFRs experience slower anticoagulation reversal. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Warfarin pharmacogenetics cohort (1,273 long-term warfarin users); warfarin reversal cohort (74 warfarin users admitted with INRs ≥ 4). PREDICTOR: eGFR, INR as time-dependent covariate, and their interaction in the pharmacogenetics cohort; eGFR in the reversal cohort. OUTCOMES & MEASUREMENTS: In the pharmacogenetics cohort, hemorrhagic (serious, life-threatening, and fatal bleeding) risk was assessed using proportional hazards regression. In the reversal cohort, anticoagulation reversal was assessed from changes in INR, warfarin and metabolite concentrations, clotting factors (II, VII, IX, and X), and PIVKA-II (protein induced by vitamin K absence or antagonist II) levels at presentation and after reversal, using linear regression and path analysis. RESULTS: In the pharmacogenetics cohort, 454 (35.7%) had eGFRs < 60 mL/min/1.73 m(2). There were 137 hemorrhages in 119 patients over 1,802 person-years of follow-up (incidence rate, 7.6 [95% CI, 6.4-8.9]/100 person-years). Patients with lower eGFRs had a higher frequency of INR ≥ 4 (P<0.001). Risk of hemorrhage was affected significantly by eGFR-INR interaction. At INR<4, there was no difference in hemorrhage risk by eGFR (all P ≥ 0.4). At INR≥4, patients with eGFRs of 30 to 44 and < 30 mL/min/1.73 m(2) had 2.2-fold (95% CI, 0.8-6.1; P=0.1) and 5.8-fold (95% CI, 2.9-11.4; P<0.001) higher hemorrhage risks, respectively, versus those with eGFRs ≥ 60 mL/min/1.73 m(2). In the reversal cohort, 35 (47%) had eGFRs < 45 mL/min/1.73 m(2). Patients with eGFRs < 45 mL/min/1.73 m(2) experienced slower anticoagulation reversal as assessed by INR (P=0.04) and PIVKA-II level (P=0.008) than those with eGFRs ≥ 45 mL/min/1.73 m(2). LIMITATIONS: Limited sample size in the reversal cohort, unavailability of antibiotic use and urine albumin data. CONCLUSIONS: Patients with lower eGFRs have differentially higher hemorrhage risk at INR ≥ 4. Moreover, because the INR reversal rate is slower, hemorrhage risk is prolonged.

Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz.

African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts. Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4(+) T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4(+) T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.

Multireader evaluation of lesion conspicuity in small pancreatic adenocarcinomas: complimentary value of iodine material density and low keV simulated monoenergetic images using multiphasic rapid kVp-switching dual energy CT.

OBJECTIVE: Perform multireader analysis of objective and subjective lesion conspicuity for small pancreatic adenocarcinomas using rapid switching dual energy CT (rsDECT). MATERIALS AND METHODS: With IRB approval, 51 abdominal multiphasic rsDECT scans in 46 subjects with small (<3 cm) pancreatic adenocarcinomas were retrospectively reviewed by three independent readers for objective and subjective lesion conspicuity. Measured variables during individual, blinded interpretive sessions of separate low (52) keV, PACS-equivalent (70) keV, and iodine material density (MD) image sets included Hounsfield units (HU) and mg/cc iodine for tumor, nontumoral pancreas, and subcutaneous fat. Objective measures included absolute lesion contrast (LC) and contrast to noise ratios (CNR). Subjective measures included image quality, lesion conspicuity, and reader confidence. Reader agreement was measured with kappa statistic; correlation with truth by Pearson coefficient, CNR with repeated mANOVA; subjective quality measures utilized Tukey-Cramer corrections for multiple testing, p < 0.05 considered significant. RESULTS: Demographics: 26 F, 20 M, mean age 68 years, weight 75 kg, tumor size of 2.3 cm. LC was highest on 52 keV images for all three readers (mean 90.1 HU). Mean CNR for iodine MD images (4.87) was significantly higher than 52 keV (4.13) or 70 keV (3.9). Very high to near-perfect kappa values were observed for all individual measured objective variables but were best for 52 keV images (52 keV 0.89-0.95, 70 keV 0.76-0.83, iodine 0.87-0.92). 70 keV images scored best for subjective image quality; iodine MD images scored best for lesion conspicuity and reader confidence. CONCLUSION: We observed very high reader agreement for independent objective rsDECT image variables and subjective rsDECT image scores in patients with small pancreatic adenocarcinomas. Maximal objective tumor to nontumoral LC was depicted on 52 keV and highest CNR on iodine MD images; readers scored the iodine MD images best for lesion conspicuity and confidence.

The impact of absent A1 segment on ischemic stroke characteristics and outcomes.

BACKGROUND: A1 segment is the proximal portion of anterior cerebral artery. Absence of the A1 segment can compromise anterior cerebral collateral blood flow. Few studies have examined the association of an absent A1 segment and ischemic stroke outcome. We sought to determine the association between A1 absence and affected vessel territory, stroke volume, and outcomes among patients with acute ischemic stroke (AIS). METHODS: A retrospective review of prospectively identified patients with AIS from July 2008 to March 2013 was performed. Patients without intracranial vascular imaging were excluded. We compared patients with absent A1 to patients with bilateral A1 segments in terms of demographics, stroke severity (as measured by National Institute of Health Stroke Scale [NIHSS]), vascular distribution, and in-hospital mortality using the chi-square test and logistic regression. RESULTS: Of the 1146 patients with AIS and intracranial vascular imaging, 5.9% patients (n = 68) had absent A1. Compared with other AIS patients, those with absent A1 were older (65 vs. 63 years old, respectively, P = .016). There was no difference between groups in terms of the vascular distribution or the side of the stroke. The median volume of the infracted tissue was similar across the groups even when it was stratified according to the Treatment of Acute Stroke Trial classification. Patients with an absent A1 had twice higher odds of in-hospital mortality (odds ratio, 2.4; 95% confidence interval, 1.1-5.2; P = .028); however, significance was lost after adjusting to age, NIHSS at baseline, and glucose on admission. Other outcome measures were similar across the groups. CONCLUSIONS: In our sample, patients with an absent A1 segment did not have a specific vascular distribution, larger infarct volume, or worse outcomes.

Early therapy assessment of combined anti-DR5 antibody and carboplatin in triple-negative breast cancer xenografts in mice using diffusion-weighted imaging and (1)H MR spectroscopy.

PURPOSE: To assess the early response of triple-negative breast-cancer (TNBC) following TRA-8 and carboplatin therapy using DWI and MRS in 2LMP and SUM159 mouse models. MATERIALS AND METHODS: Four groups (n = 5/group) of each model were untreated or treated with carboplatin, TRA-8, and combination, respectively. DWI and MRS were applied on 0, 3, and 7 days after therapy initiation, and all tumors were collected thereafter for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. The changes in intratumoral apparent diffusion coefficient (ADC) and fat-water ratios (FWRs) were compared with tumor volume changes and apoptotic cell densities. RESULTS: Mean ADC values of 2LMP and SUM159 tumors significantly increased 4 ± 4% and 37 ± 11% during 7 days of combination therapy, respectively, as compared to control groups (P < 0.05). Similarly, mean FWRs of 2LMP and SUM159 tumors significantly increased 102 ± 30% and 126 ± 52%, respectively, for 7 days of combined treatment (P < 0.05). The changes of the mean ADC values for 3 days (or FWRs for 7 days) were linearly proportional to either the mean volume changes or apoptotic cell densities in both models. CONCLUSION: DWI and MRS assessed the early tumor response to TRA-8 and carboplatin in TNBC mouse models.

Persistent leukocytosis-is this a persistent problem for patients with acute ischemic stroke?

BACKGROUND: In the setting of acute ischemic stroke (AIS), leukocytosis has been shown to be an indicator of inflammatory response. Although leukocytosis on admission has been shown to correlate with initial stroke severity in AIS patients, no work has been done to assess if there are differences in transient or persistent leukocytosis in patients without infection. The objective of this study is to determine the clinical significance of persistent versus transient leukocytosis during the early phase of AIS. METHODS: Patients who presented with AIS to our center within 48 hours of symptom onset between July 2008 and June 2010 were retrospectively identified by chart review. Patients were included if they had leukocytosis on admission (defined as white blood cell count >11,000/µL based on laboratory reference range values). A logistic regression model was used to evaluate persistent leukocytosis (leukocytosis 48 hours after admission) as a predictor of several outcome measures, including good functional outcome (discharge modified Rankin Scale score of 0-2). Marginal effects were used to estimate the probability of poor functional outcome. RESULTS: Of the 438 patients screened, 49 had leukocytosis on admission and of those 24 (49%) had persistent leukocytosis. NIHSS score correlated significantly with persistence of leukocytosis (r = .306; P = .0044). More people with transient leukocytosis (leukocytosis lasting <48 hours) had a good functional outcome (44% versus 16%; P = .006). After adjusting for baseline NIHSS score, persistent leukocytosis was not a significant independent predictor of good functional outcome, but showed an association (OR, 2.5; 95% CI, .562-10.7; P = .2322). Persistent leukocytosis after adjusting for age and NIHSS score at admission is associated with a poor functional outcome, but it is not statistically significant (OR, 2.43; 95% CI, .59-9.87; P = .2151). After controlling for age and NIHSS score on admission, for patients with persistent leukocytosis, the probability of having poor functional outcome at discharge was increased by 16 percentage points. CONCLUSIONS: Persistent leukocytosis is associated with higher baseline NIHSS scores. Persistent leukocytosis is tightly linked with baseline stroke severity and is associated with poor patient outcomes. Our study found that patients with persistent leukocytosis are more likely to present with severe strokes and maintain a high NIHSS score at 24 hours after admission, unlike patients without leukocytosis or patients with transient leukocytosis. Furthermore, it appears that persistent leukocytosis outside the setting of an infection negatively impacts the short-term functional outcome of AIS patients. Identifying patients with persistent leukocytosis could help to prognosticate and target patients that may benefit from future anti-inflammatory interventions.

Predictors of systemic inflammatory response syndrome in ischemic stroke undergoing systemic thrombolysis with intravenous tissue plasminogen activator.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is an inflammatory process associated with poor outcomes in acute ischemic stroke (AIS) patients. However, no study to date has investigated predictors of SIRS in AIS patients treated with intravenous (IV) tissue plasminogen activator (tPA). METHODS: Consecutive patients were retrospectively reviewed for evidence of SIRS during their acute hospitalization. SIRS was defined as the presence of 2 or more of the following: (1) body temperature less than 36°C or greater than 38°C, (2) heart rate greater than 90, (3) respiratory rate greater than 20, or (4) white blood cell count less than 4000/mm or greater than 12,000/mm or more than 10% bands for more than 24 hours. Those diagnosed with an infection were excluded. A scoring system was created to predict SIRS based on patient characteristics available at the time of admission. Logistic regression was used to evaluate potential predictors of SIRS using a sensitivity cutoff of ≥65% or area under the curve of .6 or more. RESULTS: Of 212 patients, 44 had evidence of SIRS (21%). Patients with SIRS were more likely to be black (61% versus 54%; P = .011), have lower median total cholesterol at baseline (143 versus 167 mg/dL; P = .0207), and have history of previous stroke (51% versus 35%; P = .0810). Ranging from 0 to 6, the SIRS prediction score consists of African American (2 points), history of hypertension (1 point), history of previous stroke (1 point), and admission total cholesterol less than 200 (2 points). Patients with an SIRS score of 4 or more were 3 times as likely to develop SIRS when compared with patients with a score of ≤3 (odds ratio = 2.815, 95% confidence interval 1.43-5.56, P = .0029). CONCLUSIONS: In our sample of IV tPA-treated AIS patients, clinical and laboratory characteristics available on presentation were able to identify patients likely to develop SIRS during their acute hospitalization. Validation is required in other populations. If validated, this score could assist providers in predicting who will develop SIRS after treatment with IV tPA.

Racial and gender differences in stroke severity, outcomes, and treatment in patients with acute ischemic stroke.

BACKGROUND: Previous research has indicated that women and blacks have worse outcomes after acute ischemic stroke (AIS). Little research has been done to investigate the combined influence of race and gender in the presentation, treatment, and outcome of patients with AIS. We sought to determine the association of race and gender on initial stroke severity, thrombolysis, and functional outcome after AIS. METHODS: AIS patients who presented to 2 academic medical centers in the United States (2004-2011) were identified through prospective registries. In-hospital strokes were excluded. Stroke severity, measured by admission National Institutes of Health Stroke Scale (NIHSS) scores, treatment with tissue plasminogen activator (tPA), neurologic deterioration (defined by a ≥2-point increase in NIHSS score), and functional outcome at discharge, measured by the modified Rankin Scale, were investigated. These outcomes were compared across race/gender groups. A subanalysis was conducted to assess race/gender differences in exclusion criteria for tPA. RESULTS: Of the 4925 patients included in this study, 2346 (47.6%) were women and 2310 (46.9%) were black. White women had the highest median NIHSS score on admission (8), whereas white men had the lowest median NIHSS score on admission (6). There were no differences in outcomes between black men and white men. A smaller percentage of black women than white women were treated with tPA (27.6% versus 36.6%, P < .0001), partially because of a greater proportion of white women presenting within 3 hours (51% versus 45.5%, P = .0005). Black women had decreased odds of poor functional outcome relative to white women (odds ratio [OR] = .85, 95% confidence interval [CI] .72-1.00), but after adjustment for baseline differences in age, NIHSS, and tPA use, this association was no longer significant (OR = 1.2, 95% CI .92-1.46, P = .22). Black women with an NIHSS score less than 7 on admission were at lower odds of receiving tPA than the other race/gender groups, even after adjusting for arriving within 3 hours and admission glucose (OR = .66, 95% CI .44-.99, P = .0433). CONCLUSION: Race and gender were not significantly associated with short-term outcome, although black women were significantly less likely to be treated with tPA. Black women had more tPA exclusions than any other group. The primary reason for tPA exclusion in this study was not arriving within 3 hours of stroke symptom onset. Given the growth in incident strokes projected in minority groups in the next 4 decades, identifying factors that contribute to black women not arriving to the emergency department in time are of great importance.

Tests of Mediation: Paradoxical Decline in Statistical Power as a Function of Mediator Collinearity.

Increasing the correlation between the independent variable and the mediator (a coefficient) increases the effect size (ab) for mediation analysis; however, increasing a by definition increases collinearity in mediation models. As a result, the standard error of product tests increase. The variance inflation due to increases in a at some point outweighs the increase of the effect size (ab) and results in a loss of statistical power. This phenomenon also occurs with nonparametric bootstrapping approaches because the variance of the bootstrap distribution of ab approximates the variance expected from normal theory. Both variances increase dramatically when a exceeds the b coefficient, thus explaining the power decline with increases in a. Implications for statistical analysis and applied researchers are discussed.

A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using magnetic resonance imaging, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n=24, 13 males, 11 females) and standard (n=17, 8 males, 9 females) diets. Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A Diet X Age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.

Systemic inflammatory response syndrome in tissue-type plasminogen activator-treated patients is associated with worse short-term functional outcome.

BACKGROUND AND PURPOSE: Systemic inflammatory response syndrome (SIRS) is a generalized inflammatory state. The primary goal of the study was to determine whether differences exist in outcomes in SIRS and non-SIRS intravenous tissue-type plasminogen activator-treated patients. METHODS: Consecutive patients were retrospectively reviewed for the evidence of SIRS during their admission. SIRS was defined as the presence of ≥2 of the following: body temperature<36°C or >38°C, heart rate>90, respiratory rate>20, and white blood cells<4000/mm or >12 000 mm, or >10% bands. Patients diagnosed with infection (via positive culture) were excluded. RESULTS: Of the 241 patients, 44 had evidence of SIRS (18%). Adjusting for pre-tissue-type plasminogen activator National Institutes of Health Stroke Scale, age, and race, SIRS remained a predictor of poor functional outcome at discharge (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.16-5.73; P=0.0197). CONCLUSIONS: In our sample of tissue-type plasminogen activator-treated (tPA) patients, ~1 in 5 patients developed SIRS. Furthermore, we found the presence of SIRS to be associated with poor short-term functional outcomes and prolonged length of stay.