International practice variation in perioperative laboratory testing in glioblastoma patients—a retrospective cohort study

Purpose Although standard-of-care has been defined for the treatment of glioblastoma patients, substantial practice variation exists in the day-to-day clinical management. This study aims to compare the use of laboratory tests in the perioperative care of glioblastoma patients between two tertiary academic centers—Brigham and Women’s Hospital (BWH), Boston, USA, and University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. Methods All glioblastoma patients treated according to standard-of-care between 2005 and 2013 were included. We compared the number of blood drawings and laboratory tests performed during the 70-day perioperative period using a Poisson regression model, as well as the estimated laboratory costs per patient. Additionally, we compared the likelihood of an abnormal test result using a generalized linear mixed effects model. Results After correction for age, sex, IDH1 status, postoperative KPS score, length of stay, and survival status, the number of blood drawings and laboratory tests during the perioperative period were 3.7-fold (p < 0.001) and 4.7-fold (p < 0.001) higher, respectively, in BWH compared to UMCU patients. The estimated median laboratory costs per patient were 82 euros in UMCU and 256 euros in BWH. Furthermore, the likelihood of an abnormal test result was lower in BWH (odds ratio [OR] 0.75, p < 0.001), except when the prior test result was abnormal as well (OR 2.09, p < 0.001). Conclusions Our results suggest a substantially lower clinical threshold for ordering laboratory tests in BWH compared to UMCU. Further investigating the clinical consequences of laboratory testing could identify over and underuse, decrease healthcare costs, and reduce unnecessary discomfort that patients are exposed to.

DOZ047.51: Swallowing and pulmonary diagnoses in children with EA and TEF

Introduction Children with repaired congenital esophageal atresia/tracheoesophageal fistula (EA/TEF) are at high risk of aerodigestive morbidity. We hypothesized that age and coexisting pulmonary diagnoses are associated with dysphagia in this population. Methods Retrospective review of children with EA/TEF seen in the aerodigestive program between 2011 and 2015 was carried out and comorbidities, video fluoroscopic swallow studies (VFSS), chest CT, and bronchoscopy results were reviewed. VFSS was considered abnormal if there was aspiration, deep laryngeal penetration, significant residue, or delayed initiation. Mann–Whitney U test was used to examine VFSS results by age. Fisher's exact test was used to assess the relationship between VFSS result and comorbidities. Results Ninety VFSS were performed on 44 children with EA/TEF (median 2 studies per patient, range: 0–7). Fifty three percent (23/39) children had at least one abnormal VFSS. Seventeen children had VFSS change between normal and abnormal over time, with 11 normal on their most recent VFSS. Younger children (Mdn = 1.57 years) were more likely to have an abnormal test result than older children (Mdn = 3.55 years) (p = 0.001). Children with severe tracheomalacia (>90% tracheal collapse visualized on flexible bronchoscopy) had a higher incidence of abnormal VFSS (14/20; 70%) than the other children with EA/TEF (9/24; 38%) (P = 0.04). Children with other pulmonary and airway comorbidities, including gestation age <36 weeks (P = 0.24), vocal fold immobility (P = 0.1), abnormal chest CT (P = 0.1), tended to have an increased incidence of abnormal VFSS but did not reach statistical significance in this cohort. Discussion Dysphagia was prevalent in this cohort and related to age and severe tracheomalacia. This reinforces the need for a multidisciplinary evaluation including feeding and swallowing evaluation. In this rare disease, we must collaborate between sites to improve our understanding of aerodigestive diagnoses and disease outcomes.

Developing Software to “Track and Catch” Missed Follow-up of Abnormal Test Results in a Complex Sociotechnical Environment

SummaryBackground: Abnormal test results do not always receive timely follow-up, even when providers are notified through electronic health record (EHR)-based alerts. High workload, alert fatigue, and other demands on attention disrupt a provider’s prospective memory for tasks required to initiate follow-up. Thus, EHR-based tracking and reminding functionalities are needed to improve follow-up.Objectives: The purpose of this study was to develop a decision-support software prototype enabling individual and system-wide tracking of abnormal test result alerts lacking follow-up, and to conduct formative evaluations, including usability testing.Methods: We developed a working prototype software system, the Alert Watch And Response Engine (AWARE), to detect abnormal test result alerts lacking documented follow-up, and to present context-specific reminders to providers. Development and testing took place within the VA’s EHR and focused on four cancer-related abnormal test results. Design concepts emphasized mitigating the effects of high workload and alert fatigue while being minimally intrusive. We conducted a multifaceted formative evaluation of the software, addressing fit within the larger socio-technical system. Evaluations included usability testing with the prototype and interview questions about organizational and workflow factors. Participants included 23 physicians, 9 clinical information technology specialists, and 8 quality/safety managers.Results: Evaluation results indicated that our software prototype fit within the technical environment and clinical workflow, and physicians were able to use it successfully. Quality/safety managers reported that the tool would be useful in future quality assurance activities to detect patients who lack documented follow-up. Additionally, we successfully installed the software on the local facility’s “test” EHR system, thus demonstrating technical compatibility.Conclusion: To address the factors involved in missed test results, we developed a software prototype to account for technical, usability, organizational, and workflow needs. Our evaluation has shown the feasibility of the prototype as a means of facilitating better follow-up for cancer-related abnormal test results.

Sensitivity of a New Global Assay for Protein C (PC) Pathway Abnormalities and Potential Significance of an Abnormal Test Result as a Risk Factor/Marker for Thrombosis Independently of Its Sensitivity for PC Pathway Abnormalities.

Abnormalities of the protein C (PC) anticoagulant pathway i.e. PC deficiency, PS deficiency and APC-resistant factor Va (FV Leiden) are among the most frequent biological risk factors for venous thromboembolism (VTE) in Caucasian patients but normal results are found in more more than 70% of the cases. This highlights the potential usefulness of a simple assay to screen globally for these abnormalities as this would rationalize the use of expensive individual assays. The HemosIL Thrombopath (Instrumentation Laboratory) is a new chromogenic global assay based on the ability of endogenous APC generated after activation of PC by a snake venom (Protac) to reduce the thrombin generation induced by a reagent containing tissue factor. Optical density is measured after addition of a thrombin-specific chromogenic substrate in the presence (OD A) or absence (OD B) of Protac. It is recommended by the test manufacturer to express results as the Protac-Induced Coagulation Inhibition percentage (PCI%) which corresponds to the ratio [OD B - OD A]/OD B x 100. The assay was performed on the ACL9000 analyzer (IL) using 85% as the cut-off level (PCI%) as we previously determined. Using various lyophilized plasma samples (n=8) both in the normal and abnormal ranges, the within-run precision (evaluated as the CV%, n=17) was found in the range from 1.2% to 2.8% and the between-run precision (CV%, n=48) in the range from 1.6% to 6.3%. The assay sensitivity for PC pathway abnormalities was studied by evaluating a selection of frozen plasma samples from 144 patients with a history of VTE (to be expended). All patients with FV Leiden, PC deficiency (1 with a borderline value), combined defects and lupus anticoagulant (LA) had a decreased response to the assay (PCI% &lt;85%), and the same applied to 28 of the 36 patients with PS deficiency. However, 6 of the 40 patients without any PC pathway abnormality had a decreased response to the assay. So the test sensitivity for PC pathway abnormalities was 91.4% (95%CI=84.2–96), its specificity 85.0% (95%CI=70.2–94.3), its negative predictive value 79.1% (95%CI=63.9–90) and its positive predictive value 94.1% (95%CI=87.5–97.8). Moreover, most (69%) of 13 additional patients carrying the G20210A prothrombin mutation had a decreased test result. PC Def. (n=20) PS Def. (n=36) PC+PS Def. (n=8) FV Leiden (n=27) LA (n=13) No Abnormality (n=40) PCI% (Med/Range) 71.8 (53.8 – 85.3) 74.3 (48.5 – 95.3) 43.5 (19.9 – 70.7) 69.9 (43.8 – 80.9) 69.2 (53.6 – 82.9) 90.5 (73.5 – 98.4) PCI%&lt;85 (n, %) 19/20 (95%) 28/36 (78%) 8/8 (100%) 27/27 (100%) 13/13 (100%) 6/40 (15%) In an attempt to evaluate the clinical relevance of a decreased PCI% in patients without any PC pathway abnormality, the HemosIL Thrombopath assay was performed pre-operatively in patients who underwent major orthopedic surgery. From the preliminary results available, test result was normal in all of the first 34 enrolled patients except in one woman (PCI%=54%) who developped post-operative deep vein thrombosis after total hip replacement and who had no isolated risk factor for thrombosis. This was the only thrombotic episode recorded in the series with a formal 3-month follow-up. These preliminary results suggest that the HemosIL Thrombopath assay is highly sensitive for PC pathway abnormalities and that an abnormal test result could be in itself a risk factor/marker for VTE (p&lt;0.05, Fischer’s exact test).

Failure of Computerized Impedance Plethysmography in the Diagnostic Management of Patients with Clinically Suspected Deep-Vein Thrombosis

SummaryBefore a new diagnostic modality can be introduced in clinical medicine, the validity of both a normal and abnormal test result have to be assessed prospectively in an appropriate patient group. We have evaluated the clinical validity of. a new computerized impedance plethysmography (CIP) in the diagnostic management of 381 consecutive patients with clinically suspected venous thrombosis. In patients with serially normal CIP results, the diagnosis of venous thrombosis was refuted and, consequently, they were not treated with anticoagulant therapy and all were followed up for a period of 6 months to estimate the occurrence of symptomatic venous thromboembolism.The study was prematurely terminated by the safety monitoring committee because of an unacceptably high incidence of confirmed venous thromboembolism (10 patients, 3.2%; 95% confidence interval: 1.6% to 6%), including 4 episodes of fatal pulmonary embolism. In a subsequent explanatory study using ultrasonography in 29 other symptomatic patients who had at least 2 repeated normal CIP test results, the failure of CIP to detect proximal vein thrombosis was confirmed in 4 patients (14%). The reasons for this failure are probably related to the use of a modified device to measure impedance in the CIP apparatus, resulting in a lower ability to separate patients without venous thrombosis from those with the disease.We concluded that CIP is insensitive for the detection of proximal vein thrombosis and, therefore, not clinically useful in the diagnostic management of patients with suspected venous thrombosis.

Dynamic Posturography and Caloric Test Results Patients with and without Vertigo

Patients with Dizziness Were Evaluated with Caloric Stimulation and with Dynamic Platform Posturography (Neurocom Equltest). The Ability of These Tests To Detect Abnormalities in Patients with and Without Vertigo Was Assessed. In 159 Patients, roughly a third had abnormal calorics while half experienced one or more “falls” during posturography. Calorics revealed proportionately more abnormalities in patients with vertigo, whereas posturography alone did not distinguish between patients with or without vertigo. Posturography did, however, Identify abnormalities in a third of patients with normal calorics, regardless of their history of vertigo. Overall, more patients with vertigo had at least one abnormal test result (70%) compared with patients without vertigo (47%). We conclude that caloric abnormalities correlate with a history of vertigo, whereas posturographic deficits can be Identified regardless of the presence of vertigo.

Effectiveness of an outpatient urine screening program.

We evaluated the effectiveness of a routine outpatient urinalysis screening program on a sample population of 2600 patients. The 189 abnormal urine results found in 182 patients were followed up by study of any new clinical and laboratory investigations or therapeutic modifications initiated on the basis of any abnormal test result. The urinalysis screening program appeared to have significant bearing on diagnosis or treatment in only 13 patients. Abnormalities found in 150 of the 182 patients were either not noted or no further positive action was taken. Thus we concluded that under the conditions of this study the urine screening program added to hospital costs without significant benefit to the patient.