Suryanarayana Pothula

Prothrombin Time and Activated Partial Thromboplastin Time Testing: A Comparative Effectiveness Study in a Million-Patient Sample

Background A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful. Methods and Findings We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7%) had one or both tests done and history and physical (H&P) records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing. Conclusions This study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk). Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests. Use of unnecessary screening tests raises concerns for the costs of such testing and the consequences of false positive results.

Neural Network Prediction of ICU Length of Stay Following Cardiac Surgery Based on Pre-Incision Variables

Background Advanced predictive analytical techniques are being increasingly applied to clinical risk assessment. This study compared a neural network model to several other models in predicting the length of stay (LOS) in the cardiac surgical intensive care unit (ICU) based on pre-incision patient characteristics. Methods Thirty six variables collected from 185 cardiac surgical patients were analyzed for contribution to ICU LOS. The Automatic Linear Modeling (ALM) module of IBM-SPSS software identified 8 factors with statistically significant associations with ICU LOS; these factors were also analyzed with the Artificial Neural Network (ANN) module of the same software. The weighted contributions of each factor (“trained” data) were then applied to data for a “new” patient to predict ICU LOS for that individual. Results Factors identified in the ALM model were: use of an intra-aortic balloon pump; O2 delivery index; age; use of positive cardiac inotropic agents; hematocrit; serum creatinine ≥ 1.3 mg/deciliter; gender; arterial pCO2. The r2 value for ALM prediction of ICU LOS in the initial (training) model was 0.356, p <0.0001. Cross validation in prediction of a “new” patient yielded r2 = 0.200, p <0.0001. The same 8 factors analyzed with ANN yielded a training prediction r2 of 0.535 (p <0.0001) and a cross validation prediction r2 of 0.410, p <0.0001. Two additional predictive algorithms were studied, but they had lower prediction accuracies. Our validated neural network model identified the upper quartile of ICU LOS with an odds ratio of 9.8(p <0.0001). Conclusions ANN demonstrated a 2-fold greater accuracy than ALM in prediction of observed ICU LOS. This greater accuracy would be presumed to result from the capacity of ANN to capture nonlinear effects and higher order interactions. Predictive modeling may be of value in early anticipation of risks of post-operative morbidity and utilization of ICU facilities.

Anesthesiologists’ Preferences regarding Visitor Presence during Placement of Neuraxial Labor Analgesia

Introduction Neuraxial labor analgesia has become an integral part of modern obstetric anesthetic practice. Presence of a familiar person during its placement may be beneficial to the patient. A survey was sent to anesthesiologists practicing obstetric anesthesia in the USA to determine their views. Methods The survey queried the following: existence of a written policy; would they allow a visitor; visitors view, sitting or standing; reasons to allow or not allow a visitor; and influence by other staff on the decision. The responses were analyzed using multiple chi-square analyses. Results Most practitioners supported allowing a visitor during placement. Reduction of patient anxiety and fulfillment of patient request were the major reasons for allowing a visitor. Sitting position and no view of the workspace were preferred. Visitor interference and safety were cited as the major reasons for precluding a visitor. Nonanesthesia providers rarely influenced the decision. Epidural analgesia was the preferred technique. Essentially no bias was found in the responses; there was statistical uniformity regardless of procedures done per week, years in practice, professional certification, geographic region (rural, urban, or suburban), or academic, private, or government responders. Conclusion The practice of visitor presence during the placement of neuraxial labor analgesia is gaining acceptance.

Non-typhoidal Salmonella abscess in a patient with a large thymoma: a rare presentation and review of the literature.

Salmonella infection commonly occurs in the gastrointestinal tract secondary to fecal-oral transmission of the bacterium. Extraintestinal Salmonella is typically seen in the biliary system and is very rarely observed in the thoracic cavity. Salmonella infection in the thymus is an even more unusual presentation of extraintestinal Salmonella, with only one previous case reported in the literature. Thymic abscesses are already a rare clinical entity and have been reported to result from infection with Staphylococcus aureus. We report a case of a 59-year-old man with a non-typhoidal Salmonella infection of a large symptomatic thymoma that was treated with surgical drainage and antibiotic therapy.

Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood

There is the need for a clinical assay to determine the extent to which a patients blood is effectively anticoagulated by the low-molecular-weight-heparin (LMWH), enoxaparin. There are also urgent clinical situations where it would be important if this could be determined rapidly. The present assay is designed to accomplish this. We only assayed human blood samples that were spiked with known concentrations of enoxaparin. The essential feature of the present assay is the quantification of the efficacy of enoxaparin in a patients blood sample by degrading it to complete inactivity with heparinase. Two blood samples were drawn into Vacutainer tubes (Becton-Dickenson; Franklin Lakes, NJ) that were spiked with enoxaparin; one sample was digested with heparinase for 5 min at 37 °C, the other sample represented the patients baseline anticoagulated status. The percent shortening of clotting time in the heparinase-treated sample, as compared to the baseline state, yielded the anticoagulant contribution of enoxaparin. We used the portable, battery operated Hemochron 801 apparatus for measurements of clotting times (International Technidyne Corp., Edison, NJ). The apparatus has 2 thermostatically controlled (37 °C) assay tube wells. We conducted the assays in two types of assay cartridges that are available from the manufacturer of the instrument. One cartridge was modified to increase its sensitivity. We removed the kaolin from the FTK-ACT cartridge by extensive rinsing with distilled water, leaving only the glass surface of the tube, and perhaps the detection magnet, as activators. We called this our minimally activated assay (MAA). The use of a minimally activated assay has been studied by us and others. 2-4 The second cartridge that was studied was an activated partial thromboplastin time (aPTT) assay (A104). This was used as supplied from the manufacturer. The thermostated wells of the instrument were used for both the heparinase digestion and coagulation assays. The assay can be completed within 10 min. The MAA assay showed robust changes in clotting time after heparinase digestion of enoxaparin over a typical clinical concentration range. At 0.2 anti-Xa I.U. of enoxaparin per ml of blood sample, heparinase digestion caused an average decrease of 9.8% (20.4 sec) in clotting time; at 1.0 I.U. per ml of enoxaparin there was a 41.4% decrease (148.8 sec). This report only presents the experimental application of the assay; its value in a clinical setting must still be established.

Antiplatelet and Anticoagulant Prophylaxis and Postoperative Blood Loss in Cardiac Surgery: In Response

We read with interest the article by Pothula et al. (1) investigating effects had by preoperative ADP antagonists with or without heparin on postoperative blood loss after cardiac surgery. This is an important issue because anesthesiologists are increasingly confronted with patients on platelet-active drugs. The authors found that patients receiving ADP antagonists and additional low-dose heparin exhibited a significantly minor blood loss as compared with the control group and the group receiving only ADP antagonists. This result was explained by a possible beneficial effect of heparin in preventing formation of microemboli and thus preserving coagulation factors until the postoperative period. This assumption is interesting, since exogenous heparin or endogenous heparinoids are usually associated with increased bleeding and all patients were on full heparin dosage during CBP. Furthermore, with the exception of fibrinogen, no coagulation factor was measured preor postoperatively. In addition, the authors made no attempt to measure platelet function preoperatively, which seems necessary to guarantee that groups are comparable. Clopidogrel is six times more potent than ticlopidine and shows linear pharmacokinetics, while ticlopidine does not (2). However, clopidogrel-induced platelet inhibition exhibits considerable individual heterogeneity (3). Furthermore, it is not clear how many patients in each group received clopidogrel or ticlopidine or whether patients received one single or repeated doses, which influences half-life, especially for ticlopidine. Why did 13% of patients in the treatment groups receive aprotinin and 4.3% the combination of aprotinin and -aminocaproic acid, while this was true for 9% and 0% of control patients, respectively? Data from animal experiments show that aprotinin partially reverses effects of thienopyridines in a dose-dependent manner (4). Lastly, concentrations of fibrinogen already varied considerably between groups at baseline. Although differences in aortic cross-clamping time and extracorporeal circulation time were investigated as possible confounders, the obvious difference in preoperative fibrinogen concentrations did not correlate with the amount of blood loss. Since intraoperative blood loss was equal in all groups, it was to be expected that postoperative concentrations of fibrinogen would correlate well with preoperative values in all groups (5), provided that fluid therapy, which itself influences hemostasis, was also comparable between groups. Consequently, the causal relationship between platelet antagonists with or without heparin therapy and the reported postoperative blood loss seems quite questionable. Moreover, since several confounders cannot be excluded, results should be interpreted with caution.