Postoperative complications and hospital costs following open radical cystectomy: A retrospective study.

OBJECTIVES: To evaluate primarily the relationship between postoperative complications and hospital costs, and secondarily the relationship between postoperative complications and mortality, following radical cystectomy. METHODS: Postoperative complications were retrospectively examined for 147 patients undergoing radical cystectomy at a university hospital between January 2012 and July 2021. Complications were defined and graded using the Clavien-Dindo classification system. In-hospital cost was calculated using an activity-based costing methodology. Regression modelling was used to investigate the relationships among a priori selected perioperative variables, complications, and costs. The effect of complications on postoperative mortality was ascertained using time-dependent coefficients in a Cox proportional hazards regression model. RESULTS: 135 (92%) patients experienced one or more postoperative complications. The medians of hospital cost for patients who experienced no complications and those who experienced complications were $42,796.3 (29,222.9-53,532.5) and $81,050.1 (49,614.8-122,533.6) respectively, p < 0.001. Hospital costs were strongly associated with complication severity: Clavien-Dindo grade II complications increased costs by 45.2% (p < 0.001, 95% CI 19.1%-76.6%), and Clavien-Dindo grade III to V complications increased costs by 107.5% (p < 0.001, 95% CI 52.4%-181.8%). Each additional count of complication and increase in Clavien-Dindo complication grade increased the risk of mortality 1.28-fold (RR = 1.28, p = 0.006, 95% CI 1.08-1.53) and 2.50-fold (RR = 2.50, p = 0.012 95% CI 1.23-5.07) respectively. CONCLUSIONS: These findings demonstrate a high prevalence of complications following cystectomy and significant associated increases in hospital costs and mortality. Postoperative complications are a key target for cost-containment strategies. TRIAL REGISTRATION: Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN:12622000057785.

The Association of Postoperative Complications and Hospital Costs Following Distal Pancreatectomy.

Background: Understanding the financial implications associated with the complications post-distal pancreatectomy (DP) may be beneficial for the future optimisation of postoperative care pathways and improved cost-efficiency. The primary outcome of this retrospective study was the characterisation of the additional cost associated with postoperative complications following DP. The secondary outcome was the estimation of the prevalence, type and severity of complications post-DP and the determination of which complications were associated with higher costs. Methods: Postoperative complications were retrospectively examined for 62 adult patients undergoing distal pancreatectomy at an Australian university hospital between January 2012 and July 2021. Complications were defined and graded using the Clavien-Dindo (CVD) classification system. In-hospital cost of index admission was calculated using an activity-based costing methodology and was reported in US dollars at 2021 rates. Regression modelling was used to investigate the relationships among selected perioperative variables, complications and costs. Results: 45 patients (72.6%) experienced one or more postoperative complications. The median (IQR) hospital cost in US dollars was 31.6% greater in patients who experienced complications compared to those who experienced no complications ($40,717.8 [27,358.0-59,834.3] vs. $30,946.9 [23,910.8-46,828.1]). Costs for patients with four or more complications were 43.5% higher than for those with three or fewer complications (p = 0.015). Compared to patients with no complications, the median hospital costs increased by 17.1% in patients with minor complications (CVD grade I/II) and by 252% in patients who developed major complication (i.e., CVD grade III/IV) complications. Conclusion: Postoperative complications are a key target for cost-containment strategies. Our findings demonstrate a high prevalence of postoperative complications following distal pancreatectomy with number and severity of postoperative complications being associated with increased hospital costs. (Registered in the Australian New Zealand Clinical Trials Registry [No. ACTRN12622000202763]).

Thromboelastography in elective total hip arthroplasty.

BACKGROUND: Hypercoagulability plays an important role in predisposing patients to venous thromboembolism (VTE) after total hip arthroplasty (THA). We used thromboelastography (TEG) to examine the coagulation status of patients undergoing THA. AIM: To examine coagulation as measured by TEG in patients undergoing THA who received standard VTE chemoprophylaxis with enoxaparin. METHODS: After ethical approval, we performed a retrospective analysis of data collected in patients undergoing primary elective THA. We analyzed TEG data on samples performed before skin incision, intraoperatively and for 5 d postoperatively. Conventional coagulation tests were performed preoperatively and on postoperative day 5. RESULTS: Twenty patients undergoing general anesthesia and 32 patients undergoing spinal anesthesia (SA) were included. TEG demonstrated a progressively hypercoagulable state postoperatively, characterized by elevated maximum amplitude. TEG also demonstrated transient intraoperative hypercoagulability in patients receiving SA. In contrast, conventional coagulation tests were normal in all patients, pre- and postoperatively, except for an increase in plasma fibrinogen day 5 postoperatively. CONCLUSION: Despite VTE prophylaxis, patients following total hip replacement remain in a hypercoagulable state as measured by both TEG and conventional tests. This group may benefit from more optimal anticoagulation and/or additional perioperative hemostatic monitoring, via TEG or otherwise.

Fast-track recovery program after cardiac surgery in a teaching hospital: a quality improvement initiative.

OBJECTIVE: Fast-track cardiac anesthesia (FTCA) is a technique that may improve patient access to surgery and maximize workforce utilization. However, feasibility and factors impacting FTCA implementation remain poorly explored both locally and internationally. We describe the specific intraoperative and postoperative protocols for our FTCA program, assess protocol compliance and identify reasons for FTCA failure. RESULTS: We tested the program in 16 patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. There was 100% compliance with the FTCA protocols. Four (25%) patients successfully completed the FTCA protocol (extubated < 4 h postoperatively and discharged from the intensive care unit on the same operative day).

Cytokine and lipid metabolome effects of low-dose acetylsalicylic acid in critically ill patients with systemic inflammation: a pilot, feasibility, multicentre, randomised, placebo-controlled trial.

OBJECTIVE: The systemic inflammatory response syndrome (SIRS) is a dysregulated response that contributes to critical illness. Adjunctive acetylsalicylic acid (ASA) treatment may offer beneficial effects by increasing the synthesis of specialised proresolving mediators (a subset of polyunsaturated fatty acid-derived lipid mediators). DESIGN: Pilot, feasibility, multicentre, double-blind, randomised, placebo-controlled trial. SETTING: Four interdisciplinary intensive care units (ICUs) in Australia. PARTICIPANTS: Critically ill patients with SIRS. INTERVENTIONS: ASA 100 mg 12-hourly or placebo, administered within 24 hours of ICU admission and continued until ICU day 7, discharge or death, whichever came first. MAIN OUTCOME MEASURES: Interleukin-6 (IL-6) serum concentration at 48 hours after randomisation and, in a prespecified subgroup of patients, serum lipid mediator concentrations measured by mass spectrometry. RESULTS: The trial was discontinued in December 2017 due to slow recruitment and after the inclusion of 48 patients. Compared with placebo, ASA did not decrease IL-6 serum concentration at 48 hours. In the 32 patients with analysis of lipid mediators, low-dose ASA increased the concentration of 15-hydroxyeicosatetraenoic acid, a proresolving precursor of lipoxin A4, and reduced the concentration of the proinflammatory cytochrome P-dependent mediators 17-HETE (hydroxyeicosatetraenoic acid), 18-HETE and 20-HETE. In the eicosapentaenoic acid pathway, ASA significantly increased the concentration of the anti-inflammatory mediators 17,18-DiHETE (dihydroxyeicosatetraenoic acid) and 14,15-DiHETE. CONCLUSIONS: In ICU patients with SIRS, low-dose ASA did not significantly alter serum IL-6 concentrations, but it did affect plasma concentrations of certain lipid mediators. The ability to measure lipid mediators in clinical samples and to monitor the effect of ASA on their levels unlocks a potential area of biological investigation in critical care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN 12614001165673).

In adult patients with severe traumatic brain injury, does the use of norepinephrine for augmenting cerebral perfusion pressure improve neurological outcome? A systematic review.

BACKGROUND AND OBJECTIVE: Despite multiple interventions, mortality due to severe traumatic brain injury (sTBI) within mature Trauma Systems has remained unchanged over the last decade. During this time, the use of vasoactive infusions (commonly norepinephrine) to achieve a target blood pressure and cerebral perfusion pressure (CPP) has been a mainstay of sTBI management. However, evidence suggests that norepinephrine, whilst raising blood pressure, may reduce cerebral oxygenation. This study aimed to review the available evidence that links norepinephrine augmented CPP to clinical outcomes for these patients. METHODS: A systematic review examining the evidence for norepinephrine augmented CPP in TBI patients was undertaken. Strict inclusion and exclusion criteria were developed for a dedicated literature search of multiple scientific databases. Two dedicated reviewers screened articles, whilst a third dedicated reviewer resolved conflicts. RESULTS: The systematic review yielded 4,809 articles, of which 1,197 duplicate articles were removed. After abstract/title screening, 45 articles underwent full text review, resulting in the identification of two articles that investigated the effect of norepinephrine administration on clinical outcomes in patients following TBI when compared to other vasopressors. Neither study found a difference in neurological outcome between the vasopressor groups. No articles measured the effect of norepinephrine compared to no vasopressor use on the clinical outcome of patients with sTBI. CONCLUSIONS: Despite being a mainstay of pharmacological management for hypotension in patients following sTBI, there is minimal clinical evidence supporting the use of norepinephrine in targeting a CPP for either improving neurological outcomes or reducing mortality. Outcomes-based clinical trials exploring the role of brain tissue perfusion and oxygenation monitoring are required to validate any benefit.

Comparison of Thromboelastography and Conventional Coagulation Tests in Patients With Severe Liver Disease.

OBJECTIVE: Thromboelastography (TEG) may provide rapid and clinically important coagulation information in acutely ill patients with chronic liver disease (CLD). Our objective was to describe the relationship between TEG and conventional coagulation tests (CCTs), which has not been previously explored in this population. METHODS: In acutely ill patients with severe CLD (Child-Pugh score > 9, category C), we conducted a prospective observational study investigating coagulation assessment as measured by both CCTs and TEG. We used quantile regression to explore 30 associations between TEG parameters and corresponding CCTs. We compared TEG and CCT measures of coagulation initiation, clot formation, clot strength, and fibrinolysis. RESULTS: We studied 34 patients on a total of 109 occasions. We observed inconsistent associations between TEG and CCT measures of coagulation initiation: TEG (citrated kaolin [CK] assay) standard reaction time and international normalized ratio: R 2 = 0.117 (P = .044). Conversely, there were strong and consistent associations between tests of clot formation: TEG (CK) kinetics time and fibrinogen: R 2 = 0.202 (P < .0001) and TEG (CK) α angle and fibrinogen 0.263 (P < .0001). We also observed strong associations between tests of clot strength, specifically TEG MA and conventional fibrinogen levels, across all TEG assays: MA (CK) and fibrinogen: R 2 = 0.485 (P < .0001). There were no associations between TEG and D-dimer levels. CONCLUSIONS: In acutely ill patients with CLD, there are strong and consistent associations between TEG measures of clot formation and clot strength and conventional fibrinogen levels. There are weak and/or inconsistent associations between TEG and all other conventional measures of coagulation.

Association between Role Overload and Sleep Disturbance among Dementia Caregivers: The Impact of Social Support and Social Engagement.

Objective: To explore the association between role overload (RO) and sleep maintenance insomnia (SMI), and the moderation effects of social support and social engagement (SE). Methods: We report a cross-sectional study using data drawn from the 2015 National Health and Aging Trends Study and National Study of Caregiving. We used multiple regression and controlled for demographics and potential confounders. Results: Nearly 45% of caregivers reported suffering from SMI during "some" and "more" nights within the past month with one half reporting "almost" or "every" night. RO was found positively associated with the risk of SMI. Instrumental support moderated the effect of RO on SMI overall, although moderation was limited to a subsample of adult children caregivers. Discussion: The sleep quality of dementia caregivers may be affected by RO, particularly for adult children caregivers. Increasing instrumental support may be beneficial to caregiver's sleep quality.

Assessing TEG6S reliability between devices and across multiple time points: A prospective thromboelastography validation study.

The TEG6S is a novel haemostasis analyser utilising resonance technology. It offers potentially greater coagulation information and ease of use, however has not been independently validated in a clinical setting. We aimed to determine if the TEG6S is reliable between devices and across time points. We performed a prospective observational study with ethical approval. For interdevice reliability, we performed simultaneous analysis on two TEG6S devices on 25 adult ICU patients. For time point reliability, we performed repeated sampling across five different time points on 15 adult participants. Blood was collected with informed consent, or as standard care, before four-channel citrated kaolin analysis. We observed almost perfect interdevice reliability across all TEG parameters. The Lin's concordance correlation coefficients (95% CI, major axis regression slope, intercept) were R-time: 0.96 (0.92-0.99, 0.88, 0.57); K-time: 0.93 (0.87-0.98, 1.07, 0.00); Alpha Angle: 0.87 (0.78-0.96, 1.20, -14.10); Maximum Amplitude: 0.99 (0.98-0.99, 1.02, -1.38); Clot Lysis: 0.89 (0.82-0.97, 1.20, 0.07). Additionally, we observed moderate-to-high reliability across time points. Demonstrating almost perfect agreement across different devices and moderate-to-high reliability across multiple time points, suggests the TEG6S platform can be used with haemostatic accuracy and generalisability. This has potentially significant implications for clinical practice and multi-site research programs.

Prospective Longitudinal Evaluation of Coagulation with Novel Thromboelastography Technology in Patients After Subarachnoid Hemorrhage: A Pilot Study.

BACKGROUND: There is limited knowledge of whether hypercoagulability is present after subarachnoid hemorrhage (SAH) or about its timing of onset, duration, and severity. To conduct a pilot new-generation thromboelastography (TEG) technology (TEG6s)-based and conventional coagulation test-supported longitudinal assessment of coagulation in patients with SAH. METHODS: We prospectively enrolled patients with nontraumatic SAH on admission from May 2015 to May 2016. We performed TEG6s measurements and conventional coagulation tests on days 1, 2, 3, 5, 7, 10, and 14 and compared them with TEG6s parameters in healthy volunteers. RESULTS: We studied 14 patients and 72 TEG6s measurements. Of these patients, 10 (71.4%) were admitted to the intensive care unit. Mean age was 57.5 (±14.5) years, Acute Physiology and Chronic Health Evaluation III score 58.2 (±26.6), length of hospital stay was 23 (±11.7) days, and mortality was 14.3%. At baseline, conventional coagulation tests were within normal range. However, TEG6s parameters already showed increased coagulability. Thereafter, alpha angle, reaction time, functional fibrinogen level, and maximum amplitude rapidly and significantly increased (P < 0.01) compared with healthy controls. Ten (71.4%) patients demonstrated a >20% increase in coagulability based on TEG6s parameters from their baseline. Moreover, TEG6s hypercoagulability peaked at day 10 and only showed an initial partial decline towards normal by day 14. Similarly, platelet counts and fibrinogen levels increased over this period (P < 0.01) CONCLUSIONS: Using TEG6s technology, we found significant and progressive hypercoagulability in 70% of patients, with an early dominant contribution from hyperfibrinogenemia and increased fibrin formation and partial contribution from thrombocytosis, beginning on the first day, increasing to peak values by day 10, and then partly declining toward normal by day 14.

Intraoperative oxygen challenge for toleration of single lung ventilation in a patient with severe obstructive airway disease: A case report.

Perioperative risk assessment is complex in patients with chronic obstructive pulmonary disease who have undergone previous lung resection surgery. A 70-year-old female with severe chronic obstructive pulmonary disease and previous right middle and lower lobectomy, presented for left lower lobe superior segmentectomy. Respiratory function tests revealed a forced expiratory volume in 1 second of 0.72L, a forced vital capacity of 1.93L, and a carbon monoxide transfer factor of 10.0 ml/min/mmHg. A cardiopulmonary exercise test demonstrated little ventilatory reserve with profound arterial desaturation on peak exercise, however, a normal peak oxygen consumption (16.7 ml/min/kg) and a nadir minute ventilation/carbon dioxide slope of 24 implied a limited risk of perioperative cardiovascular morbidity. Given these conflicting results we performed an intraoperative oxygen challenge test under general anaesthesia with sequential ventilation of different lobes of the lung. We demonstrate the use of the oxygen challenge test as an effective intervention to further assess safety and tolerance of anaesthesia of patients with limited respiratory reserve being assessed for further complex redo lung resection surgery. Further, this test was a risk stratification tool that allowed informed decisions to be made by the patient about therapeutic options for treating their lung cancer. The prognostic value of traditional physiological parameters in patients with chronic obstructive pulmonary disease who have undergone previous lung resection surgery is uncertain. The intraoperative oxygen challenge test is another risk stratification tool to assist clinicians in assessment of safety and tolerance of anaesthesia for patients being considered for lung resection.

Non-invasive continuous haemodynamic monitoring and response to intervention in haemodynamically unstable patients during rapid response team review.

INTRODUCTION: During rapid response team (RRT) management of haemodynamic instability (HI), continuous non-invasive haemodynamic monitoring may provide supplemental physiological information. OBJECTIVES: To continuously and non-invasively obtain the cardiac index (CI) and mean arterial pressure (MAP) in patients with HI at baseline and during RRT management using the ClearSight™ device. METHODS: We performed a prospective observational study in adult patients managed by the RRT for tachycardia or hypotension or both. We assessed changes from baseline in heart rate (HR), MAP, CI, stroke volume index (SVI) and systemic vascular resistance index (SVRI) (i) at 5-minutely intervals up to 20 min, and (ii) over the entire 20-min period. We analysed patients by RRT trigger (tachycardia/hypotension) and intervention (fluid bolus therapy [FBT]/ no FBT). RESULTS: We successfully recorded the CI in 47 of 50 (94%) patients. RRT reviews triggered by hypotension rather than tachycardia had a lower baseline HR (-45.4 bpm, p = <0.0001), MAP (-16.1 mmHg, p = 0.0007) and CI (1.0 L/min/m2, p = 0.0025). Compared to baseline, in the tachycardia group, there was a small increase in MAP overall and at the 15-20 min time-block from 83.2 mmHg to 87.1 mmHg (+3.9 mmHg, p = 0.0066) and 85.5 mmHg (+2.3 mmHg, p = 0.0061), respectively. In those who received FBT, there was a statistically significant increase in MAP overall and at the 15-20 min time-block compared to baseline, from 70.1 mmHg to 73.5 mmHg (+3.4 mmHg, p = 0.0036) and 74.3 mmHg (+4.2 mmHg, p = 0.0037), respectively. However, there were no statistically significant changes in mean HR, CI, SVI, or SVRI when comparing baseline to the entire 20-min period or 5-min time-blocks within any group. CONCLUSIONS: Continuous non-invasive measurement of haemodynamics during RRT management for HI was possible for 20 min. Patients with hypotension rather than tachycardia had lower baseline HR, MAP and CI values. There was a statistically significant but small increase in MAP at the 15-20 min time-block and overall, for both the tachycardia and FBT groups.

Assessment of agreement and interchangeability between the TEG5000 and TEG6S thromboelastography haemostasis analysers: a prospective validation study.

BACKGROUND: TEG6S® and TEG5000® (Haemonetics Corp, USA) are haemostasis analysers that measure viscoelasticity properties of whole blood. Both use different mechanisms to assess similar components of the coagulation process. The aim of this study was to assess agreement and interchangeability between the TEG6S and TEG5000 analysers. METHODS: 3.5 mL whole blood was collected from 25 adult patients in a tertiary intensive care unit (ICU). Analysis was performed using TEG6S and TEG5000 haemostatic platforms. Agreement between platforms was measured using Lin's concordance coefficient (Lin's CC), further validated using intraclass correlation coefficients and reduced major axis regression (RMAR). RESULTS: Sixteen (64%) patients were male; mean (range) age: 59yo (23-86). TEG6S and TEG5000 systems were broadly interchangeable. The majority of TEG variables demonstrated almost perfect or substantial agreement and minimal proportional bias (maximum amplitude demonstrated a fixed bias). LY30%, however, demonstrated poor agreement and a proportional bias. Lin's CC coefficients (95% CI, RMAR slope, intercept) between TEG6S and TEG5000 variables were: R time: 0.78 (0.64-0.92, 0.76, 0.92); K time: 0.82 (0.69-0.94, 1.30, - 0.93); alpha angle: 0.79 (0.64-0.95, 1.04, - 1.43); maximum amplitude (MA): 0.90 (0.83-0.96, 0.99, - 5.0); LY30%: 0.34 (0.1-0.58, 0.43, 0.04). CONCLUSIONS: Adult patients with critical illness demonstrate almost perfect agreement in the R time and MA, substantial agreement in K time and alpha angle, but poor agreement in LY30%, as measured by the TEG6S and TEG5000 analysers. With the exception of LY30%, the TEG6S and TEG5000 platforms appear interchangeable. This has important implications for use in clinical practice and multi-site research programs. TRIAL REGISTRATION: ANZCRT number: 12617000062325 , registered 12/Jan17. Retrospectively registered.

Social Relationships and Salivary Telomere Length Among Middle-Aged and Older African American and White Adults.

OBJECTIVES: A common mechanism underlying premature morbidity may be accelerated biological aging as reflected by salivary telomere length (STL). This study examined the extent to which social relationships, both positive and negative, can be protective or confer risk relative to biological aging. METHOD: Data from the Health and Retirement Study and multiple regression were used to examine cross-sectional associations between STL, self-reported social support, and negative interaction (e.g., conflict, criticism) with family in a nationally representative sample of African American and non-Hispanic White middle-aged and older adults (N = 4,080). RESULTS: Social support from family was associated with shorter STL. Negative interaction with family had no main effect on STL but interactions characterized by high social support and more frequent negative interactions were associated with longer STL. Negative interaction with family was negatively associated with STL for African Americans and Whites but the magnitude of the effect was greater for African Americans. DISCUSSION: Study findings highlight the role of social relationships in physiological deterioration among middle-aged and older adults and identify a potential mechanism whereby race is linked to accelerated biological aging. Findings highlight the importance of considering positive and negative aspects of social relationships to understand the consequences of social connections for cellular aging in diverse populations.

Rapid response team review of hemodynamically unstable ward patients: The accuracy of cardiac index assessment.

PURPOSE: Intensive care doctors commonly attend rapid response team (RRT) reviews of hospital-ward patients with hemodynamic instability and estimate the patient's likely cardiac index (CI). We aimed to non-invasively measure the CI of such patients and assess the level of agreement between such measurements and clinically estimated CI categories (low <2L/min/m2, normal 2-2.99L/min/m2 or high ≥3L/min/m2). MATERIALS AND METHODS: A prospective, observational study of non-invasive measurement and clinical estimation of CI categories in 50 adult hospital-ward patients who activated the RRT for 'hemodynamic instability' (tachycardia > 100BPM or hypotension < 90mmHg or both). RESULTS: The CI was measured in 47/50(94%) patients and the mean CI was 3.5(95% CI 3.2-3.7) L/min/m2. Overall, 30(64%) patients had a high CI, 13(28%) and 4(9%) had a normal and a low CI, respectively. The level of agreement between measured and clinically estimated CI categories was low(19.2%). Sensitivity and positive predictive values of clinical estimation were low(0% and 3.3% for high CI, and 0% and 50% for low CI, respectively). CONCLUSIONS: Non-invasive CI measurement was possible in almost all hospital-ward patients triggering RRT review for hemodynamic instability. In such patients, the CI was high, and intensive care clinicians were unable to identify a low or a high CI state.

Small volume resuscitation with 20% albumin in intensive care: physiological effects : The SWIPE randomised clinical trial.

PURPOSE: We set out to assess the resuscitation fluid requirements and physiological and clinical responses of intensive care unit (ICU) patients resuscitated with 20% albumin versus 4-5% albumin. METHODS: We performed a randomised controlled trial in 321 adult patients requiring fluid resuscitation within 48 h of admission to three ICUs in Australia and the UK. RESULTS: The cumulative volume of resuscitation fluid at 48 h (primary outcome) was lower in the 20% albumin group than in the 4-5% albumin group [median difference - 600 ml, 95% confidence interval (CI) - 800 to - 400; P < 0.001]. The 20% albumin group had lower cumulative fluid balance at 48 h (mean difference - 576 ml, 95% CI - 1033 to - 119; P = 0.01). Peak albumin levels were higher but sodium and chloride levels lower in the 20% albumin group. Median (interquartile range) duration of mechanical ventilation was 12.0 h (7.6, 33.1) in the 20% albumin group and 15.3 h (7.7, 58.1) in the 4-5% albumin group (P = 0.13); the proportion of patients commenced on renal replacement therapy after randomization was 3.3% and 4.2% (P = 0.67), respectively, and the proportion discharged alive from ICU was 97.4% and 91.1% (P = 0.02). CONCLUSIONS: Resuscitation with 20% albumin decreased resuscitation fluid requirements, minimized positive early fluid balance and was not associated with any evidence of harm compared with 4-5% albumin. These findings support the safety of further exploration of resuscitation with 20% albumin in larger randomised trials. TRIAL REGISTRATION: http://www.anzctr.org.au . Identifier ACTRN12615000349549.

Racial and Ethnic Disparities in Dementia Risk Among Individuals With Low Education.

INTRODUCTION: As higher dementia prevalence in ethnic minority groups could be attributed to low education, we studied individuals with low education and explored potential factors driving dementia disparities. METHODS: We examined differences in dementia risk between low-educated non-Hispanic whites, Hispanics, and African Americans, and the impact of lifetime risk factors using data from the nationally representative Aging, Demographics, and Memory Study (N = 819). RESULTS: As indicated by Cox regression modeling, dementia risk of low-educated individuals was not significantly different between ethnic groups but was related to having an APOE e4 allele (hazard ratio [HR] 1.89), depression (HR 1.67), stroke (HR 1.60), and smoking (HR 1.32). Further, even in people with low education, every additional year of education decreased dementia risk (HR 0.95). DISCUSSION: Our findings imply that higher dementia prevalence in ethnic minorities may be attributable to low education, especially among Hispanics, in addition to other risk factors.

Next generation high throughput DNA damage detection platform for genotoxic compound screening.

Methods for quantifying DNA damage, as well as repair of that damage, in a high-throughput format are lacking. Single cell gel electrophoresis (SCGE; comet assay) is a widely-used method due to its technical simplicity and sensitivity, but the standard comet assay has limitations in reproducibility and throughput. We have advanced the SCGE assay by creating a 96-well hardware platform coupled with dedicated data processing software (CometChip Platform). Based on the original cometchip approach, the CometChip Platform increases capacity ~200 times over the traditional slide-based SCGE protocol, with excellent reproducibility. We tested this platform in several applications, demonstrating a broad range of potential uses including the routine identification of DNA damaging agents, using a 74-compound library provided by the National Toxicology Program. Additionally, we demonstrated how this tool can be used to evaluate human populations by analysis of peripheral blood mononuclear cells to characterize susceptibility to genotoxic exposures, with implications for epidemiological studies. In summary, we demonstrated a high level of reproducibility and quantitative capacity for the CometChip Platform, making it suitable for high-throughput screening to identify and characterize genotoxic agents in large compound libraries, as well as for human epidemiological studies of genetic diversity relating to DNA damage and repair.