Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue-type plasminogen activator in trauma patients.

BACKGROUND: Systemic hyperfibrinolysis is a lethal phenotype of trauma-induced coagulopathy. Its pathogenesis is poorly understood. Recent studies have support a central role of platelets in hemostasis and in fibrinolysis regulation, implying that platelet impairment is integral to the development of postinjury systemic hyperfibrinolysis. OBJECTIVE: The objective of this study was to identify if platelet function is associated with blood clot sensitivity to fibrinolysis. We hypothesize that platelet impairment of the ADP pathway correlates with fibrinolysis sensitivity in trauma patients. METHODS: A prospective observational study of patients meeting the criteria for the highest level of activation at an urban trauma center was performed. Viscoelastic parameters associated with platelet function (maximum amplitude [MA]) were measured with native thrombelastography (TEG), and TEG platelet mapping of the ADP pathway (ADP-MA). The contribution of fibrinogen to clotting was measured with TEG (angle) and the TEG functional fibrinogen (FF) assay (FF-MA). Another TEG assay containing tissue-type plasminogen activator (t-PA) (75 ng mL(-1) ) was used to assess clot sensitivity to an exogenous fibrinolytic stimulus by use of the TEG lysis at 30 min (LY30) variable. Multivariate linear regression was used to identify which TEG variable correlated with t-PA-LY30 (quantification of fibrinolysis sensitivity). RESULTS: Fifty-eight trauma patients were included in the analysis, with a median injury severity score of 17 and a base deficit of 6 mEq L(-1) . TEG parameters that significantly predicted t-PA-LY30 were related to platelet function (ADP-MA, P = 0.001; MA, P < 0.001) but not to fibrinogen (FF-MA, P = 0.773; angle, P = 0.083). Clinical predictors of platelet ADP impairment included calcium level (P = 0.001), base deficit (P = 0.001), and injury severity (P = 0.001). RESULTS AND CONCLUSIONS: Platelet impairment of the ADP pathway is associated with increased sensitivity to t-PA. ADP pathway inhibition in platelets may be an early step in the pathogenesis of systemic hyperfibrinolysis.

Improved hospital-level risk adjustment for surveillance of healthcare-associated bloodstream infections: a retrospective cohort study.

BACKGROUND: To allow direct comparison of bloodstream infection (BSI) rates between hospitals for performance measurement, observed rates need to be risk adjusted according to the types of patients cared for by the hospital. However, attribute data on all individual patients are often unavailable and hospital-level risk adjustment needs to be done using indirect indicator variables of patient case mix, such as hospital level. We aimed to identify medical services associated with high or low BSI rates, and to evaluate the services provided by the hospital as indicators that can be used for more objective hospital-level risk adjustment. METHODS: From February 2001-December 2007, 1719 monthly BSI counts were available from 18 hospitals in Queensland, Australia. BSI outcomes were stratified into four groups: overall BSI (OBSI), Staphylococcus aureus BSI (STAPH), intravascular device-related S. aureus BSI (IVD-STAPH) and methicillin-resistant S. aureus BSI (MRSA). Twelve services were considered as candidate risk-adjustment variables. For OBSI, STAPH and IVD-STAPH, we developed generalized estimating equation Poisson regression models that accounted for autocorrelation in longitudinal counts. Due to a lack of autocorrelation, a standard logistic regression model was specified for MRSA. RESULTS: Four risk services were identified for OBSI: AIDS (IRR 2.14, 95% CI 1.20 to 3.82), infectious diseases (IRR 2.72, 95% CI 1.97 to 3.76), oncology (IRR 1.60, 95% CI 1.29 to 1.98) and bone marrow transplants (IRR 1.52, 95% CI 1.14 to 2.03). Four protective services were also found. A similar but smaller group of risk and protective services were found for the other outcomes. Acceptable agreement between observed and fitted values was found for the OBSI and STAPH models but not for the IVD-STAPH and MRSA models. However, the IVD-STAPH and MRSA models successfully discriminated between hospitals with higher and lower BSI rates. CONCLUSION: The high model goodness-of-fit and the higher frequency of OBSI and STAPH outcomes indicated that hospital-specific risk adjustment based on medical services provided would be useful for these outcomes in Queensland. The low frequency of IVD-STAPH and MRSA outcomes indicated that development of a hospital-level risk score was a more valid method of risk adjustment for these outcomes.

Risk stratification for surgical site infections in Australia: evaluation of the US National Nosocomial Infection Surveillance risk index.

This study evaluated the US National Nosocomial Infection Surveillance (NNIS) risk index (RI) in Australia for different surgical site infection (SSI) outcomes (overall, in-hospital, post-discharge, deep-incisional and superficial-incisional infection) and investigated local risk factors for SSI. A SSI surveillance dataset containing 43 611 records for 13 common surgical procedures, conducted in 23 hospitals between February 2001 and June 2005, was used for the analysis. The NNIS RI was evaluated against the observed SSI data using diagnostic test evaluation statistics (sensitivity, specificity, positive predictive value, negative predictive value). Sensitivity was low for all SSI outcomes (ranging from 0.47 to 0.69 and from 0.09 to 0.20 using RI thresholds of 1 and 2 respectively), while specificity varied depending on the RI threshold (0.55 and 0.93 with thresholds of 1 and 2 respectively). Mixed-effects logistic regression models were developed for the five SSI outcomes using a range of available potential risk factors. American Society of Anaesthesiologists (ASA) physical status score >2, duration of surgery, absence of antibiotic prophylaxis and type of surgical procedure were significant risk factors for one or more SSI outcomes, and risk factors varied for different SSI outcomes. The discriminatory ability of the NNIS RI was insufficient for its use as an accurate risk stratification tool for SSI surveillance in Australia and its sensitivity was too low for it to be appropriately used as a prognostic indicator.

Confidence limits for the ratio of two rates based on likelihood scores: non-iterative method.

This paper describes a method for creating a confidence interval for the ratio of rates using the score statistic. This non-iterative and easy to apply procedure produces confidence intervals that are suitable for use with Poisson data and simulation results indicate that it is close to the nominal level for a wide range of scenarios.

The application of statistical process control charts to the detection and monitoring of hospital-acquired infections.

The monitoring of infection control indicators including hospital-acquired infections is an established part of quality maintenance programmes in many health-care facilities. However, surveillance data use can be frustrated by the infrequent nature of many infections. Traditional methods of analysis often provide delayed identification of increasing infection occurrence, placing patients at preventable risk. The application of Shewhart, Cumulative Sum (CUSUM) and Exponentially Weighted Moving Average (EWMA) statistical process control charts to the monitoring of indicator infections allows continuous real-time assessment. The Shewhart chart will detect large changes, while CUSUM and EWMA methods are more suited to recognition of small to moderate sustained change. When used together, Shewhart and EWMA methods are ideal for monitoring bacteraemia and multiresistant organism rates. Shewhart and CUSUM charts are suitable for surgical infection surveillance.

Patterns of treated non-melanoma skin cancer in Queensland--the region with the highest incidence rates in the world.

The incidence of non-melanoma skin cancer, comprising basal cell carcinoma and squamous cell carcinoma, was studied in Queensland during 1984. The world-standardised annual incidence rates (per 100,000 population) for the number of persons with non-melanoma skin cancer were estimated to be 1372 for men and 702 for women, the highest recorded incidence rates in the world. Rates in men were nearly double the rates in women and age-specific incidence rates increased curvilinearly with age. There were, on average, 1.4 skin cancers per person with non-melanoma skin cancer and the ratio of basal cell carcinomas to squamous cell carcinomas was approximately three to one. The age-standardised annual incidence rate (per 100,000 population) of basal cell carcinoma for residents of the Gold Coast was 1.83 times the Brisbane rate for men and 1.57 times that for women, indicating significant differences between the two regions. For squamous cell carcinoma the regional differences were not statistically significant. The average potential number of non-melanoma skin cancers (per person) treated during the lifetime of a cohort of 100,000 was estimated to be 0.014 for men and 0.009 for women by age 40. By age 65, these numbers increased to 0.22 for men and 0.11 for women. At age 90, these average numbers were 1.09 and 0.42, respectively. Although the incidence of non-melanoma skin cancer is much higher in the older age groups, it should be kept in mind that it also affects the younger population; 1028 Queenslanders under 40 required treatment for 2300 non-melanoma skin cancers in 1984. This study which provides baseline information about the occurrence of non-melanoma skin cancer in Queensland emphasises the importance of developing safe sun-exposure habits, detecting non-melanoma skin cancer early and protecting and restoring the atmosphere.

Assessing agreement.

Formal evaluation of the ability of clinicians and researchers to agree, for example, on the clinical assessment of patients, increasingly is becoming important. Two measures of agreement, kappa and the intraclass correlation coefficient, are described and illustrated. The calculation of confidence intervals that correspond to these statistics by means of the "bootstrap" method also is discussed.

Point estimates and confidence intervals for two-sample rank tests.

The editorial policy of most medical journals now requires authors to provide point estimates and confidence intervals in addition to P values. To compare data from two groups, the rank-sum test (for independent groups) and the signed-ranks test (for related groups) provide P values but do not give estimates for the size of the difference between the groups. Point estimates and confidence intervals, which were developed by Hodges and Lehmann, that correspond to these rank tests are described and illustrated.

Tissue distribution of gallium following administration of the gallium-maltol complex in the rat: a model for an aluminium-maltol complex of neurotoxicological interest.

The intestinal absorption and subsequent tissue distribution of aluminium-maltol, a potentially neurotoxic complex found in foods, was investigated using gallium as a marker for aluminium. Gallium or gallium-maltol labelled with 67Ga was administered orally to rats. The amount of gallium in 'blood-free' tissues was measured by correcting for gallium in residual blood and an estimate of intestinal absorption was then made by summing the values for all tissues examined. In both the test (gallium-maltol dosed) and control (gallium only dosed) experiments absorption of gallium was significantly increased in the fasted state when compared with that of the fed animals. In fasted but not in fed animals, administration of gallium-maltol doubled the amount of gallium absorbed when compared with administration of gallium alone.

Elevated serum and antral gastrin in obese (ob/ob) mice.

Elevations in serum gastrin concentration of six to seven times were found in postabsorptive 5- and 10-wk-old, but not 30- and 40-wk-old, obese mice in comparison with the appropriate lean controls. At 10 wk of age a fourfold hypergastrinemia was also evident in (ob/ob) mice denied food for 48 h. In 10-wk-old (ob/ob) mice that had eaten the same amount of food as lean mice from weaning, serum gastrin was six times that of lean controls. Antral gastrin concentration was 54% higher in fed 10-wk-old (ob/ob) mice than in lean mice. No relationship was found between alterations in serum gastrin and measures of gastrointestinal size or proliferative status. Maximal gastric acid output, expressed with respect to oxyntic mucosal dry weight, was reduced by 52% in 10-wk-old (ob/ob) mice compared with lean controls. It is concluded that the hypergastrinemia of 10-wk-old (ob/ob) mice is not caused by hyperphagia, but may be a consequence of reduced acid inhibition of gastrin release.

Monosaccharide transport by the small intestine of lean and genetically obese (ob/ob) mice.

The effect of the obese (ob/ob) genotype on monosaccharide transport in mouse small intestine has been examined, using several different methodologies, at various stages in the development of the syndrome. Evidence for an elevation of the total capacity of the small intestine for monosaccharide transport was found at 10, 20 and 40 weeks of age in obese mice by comparison with lean controls, the difference being most prominent at 20 weeks of age after the hyperphagic phase of the syndrome had ceased. No substantial alteration in transport, expressed per gram dry weight of intestine, either from luminal perfusion studies or from measurements of the kinetics of influx across the brush border was found in adult obese mice compared with lean controls. It is concluded that, in obese mice, the increased capacity of the intestine for monosaccharide transport compared with lean mice was due to increases in the total intestinal dry weight, and in the intestinal dry weight per centimetre, and not to changes in carrier activity per unit dry weight of intestine.