Sustainable Laboratory-Driven Method to Decrease Repeat, Same-Day WBC Differentials at a Tertiary Care Center.

OBJECTIVES: A CBC with WBC differential is often ordered when a CBC alone would be sufficient for patient care. Performing unnecessary WBC differentials adds to costs in the laboratory. Our objective was to implement a laboratory middleware algorithm to cancel repeat, same-day WBC differentials to achieve lasting improvements in laboratory resource allocation. METHODS: Repeat same-day WBC differentials were first canceled only on intensive care unit samples; after a successful trial period, the algorithm was applied hospital-wide. We retrospectively reviewed CBC with differential orders from pre- and postimplementation periods to estimate the reduction in WBC differentials and potential cost savings. RESULTS: The algorithm led to a monthly WBC differential cancellation rate of 5.40% for a total of 10,195 canceled WBC differentials during the cumulative postimplementation period (September 25, 2019, to December 31, 2020). Nearly all (99.94%) differentials remained canceled. Most patients only had one WBC differential canceled (range, 1-38). Savings estimates showed savings of $0.99 CAD per canceled differential and 1,060 minutes (17.7 hours) of technologist time. CONCLUSIONS: A middleware algorithm to cancel repeat, same-day WBC differentials is a simple and sustainable way to achieve lasting improvements in laboratory utilization.

Evaluation of simple and cost-effective immuno- haematological markers to predict outcome in hospitalized severe COVID-19 patients, with a focus on diabetes mellitus - A retrospective study in Andhra Pradesh, India.

BACKGROUND AND AIMS: COVID-19 pandemic has strained the health infrastructure globally, providing an opportunity to identify cost-effective biomarkers. We aimed to identify simple hematological prognostic markers in hospitalized severe COVID-19 patients with and without diabetes. METHODS: Retrospective study of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 154 patients, including diabetic subset n = 57) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for total leucocyte count (TLC), absolute neutrophil count (ANC), neutrophil lymphocyte ratio (NLR), and derived neutrophil lymphocyte ratio (dNLR) in order to prognosticate the outcome. RESULTS: Among 154 severe COVID-19 patients, significant association with mortality was seen with respect to TLC(p < 0.001), ANC (p < 0.001), NLR(p < 0.001) and dNLR(p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for TLC 8950 cells/mm3 (area under curve (AUC)-0.764, odds ratio (OR)-7.53), ANC 7679 cells/mm3 (AUC-0.789, OR-8.14), NLR 5.13 (AUC-0.741, OR-4.77), dNLR 3.44 (AUC -0.741, OR-4.43) respectively.In diabetic subset, the cut-offs for TLC was 8950 cells/mm3 (AUC -0.762, OR-14.9), ANC 6510 cells/mm3 (AUC -0.773, OR-16.8), NLR 5.13(AUC -0.678, OR-6) and dNLR 3.25(AUC -0.685, OR-4.7) respectively. CONCLUSIONS: In severe COVID-19 patients irrespective of diabetes, a simple, applicable total leucocyte count cut-off, 8950 cells/mm3 , together with easily derived cut-offs for ANC, NLR, dNLR may serve as cost-effective prognosticators of clinical outcome. A normal TLC may be misleading in the intensive care and the above applicable cut-off for TLC serves as an early warning tool for high-risk identification and better in-hospital management. Even with similar or lower cut-offs, diabetics had a higher mortality.

Current Clinical Methods for Detection of Peri-Prosthetic Joint Infection.

Background: Currently, one of the most pressing problems in the field of orthopedic surgery is peri-prosthetic joint infection [PJI]. While there are numerous ways to detect PJI, current clinical detection methods differ across institutions and have varying criteria and protocols. Some of these methods include the Modified Musculoskeletal Infection Society system, culturing, polymerase chain reaction, the determination of the presence of certain biomarkers, testing for the presence of alpha defensin peptides, and leukocyte level testing. Methods: This review summarizes the most recent publications in the field of PJI detection to highlight current strengths as well as provide future directions to find the system for the quickest, cost-effective, and most accurate way to diagnose these types of infections. Results: The results of this literature review suggest that, while each method of diagnosis has its advantages, each has various drawbacks as well. Current methods can be expensive, take days to weeks to complete, be prone to contamination, and can produce ambiguous results. Conclusions: The findings in this review emphasize the need for a more comprehensive and accurate system for diagnosing PJI. In addition, the specific comparison of advantages and drawbacks can be useful for researchers and clinicians with goals of creating new diagnostic tests for PJIs, as well as in clinical scenarios to determine the correct treatment for patients.

Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab.

BACKGROUND: Although nivolumab significantly prolongs survival of metastatic melanoma, about 10% of patients experience severe, even fatal immune-related adverse events (irAEs). Biomarkers to predict irAEs are, therefore, of great interest. OBJECTIVE: We aimed to correlate changes in routine blood count parameters to the occurrence of serious irAEs (grade 3/4 [G3/4] or lung/gastrointestinal [lung/GI] irAEs) in patients with melanoma who were treated with nivolumab. METHODS: We retrospectively analyzed data from 101 patient with melanoma treated with nivolumab from 8 institutes in Japan. We used logistic regression analyses to investigate associations between severe irAEs and fluctuations in routine blood count parameters (total white blood cell [WBC] count, relative neutrophil, monocyte, lymphocyte, and eosinophil count) during the treatment. Receiver-operating characteristic curve was used to determine a cutoff value for the blood count parameters and area under the curve (AUC). RESULTS: Univariate analysis revealed that G3/4 irAEs were associated with increased total WBC count (P=0.034, cutoff value=+27%, AUC=0.68, odds ratio [OR]=1.58) and decreased relative lymphocyte count (RLC, P=0.042, cutoff value=-23%, AUC=0.65, OR=1.65). However, multivariate analysis showed that the same factors, increased WBC count (P=0.014, cutoff value=+59.1%, AUC=0.79, OR=6.04) and decreased RLC (P=0.012, cutoff value=-32.3%, AUC=0.81, OR=5.01) were independent factors associated with lung/GI irAEs. CONCLUSIONS: Our results suggest that increased WBC count and decreased RLC are associated with G3/4 and lung/GI irAEs. Our analysis was based on the data point at which irAE occurrence was noticed and, therefore, these factors are not predictive, however, they could be a "signal" of severe irAE occurrence in patients with melanoma treated with nivolumab.

Clinical and Economic Burden of Elevated Blood Eosinophils in Patients With and Without Uncontrolled Asthma.

BACKGROUND: The European Respiratory Society and American Thoracic Society (ERS/ATS) published guidelines in 2014 for the evaluation and treatment of asthma. These guidelines draw attention to management of patients with asthma that remains uncontrolled despite therapy. One phenotypic characteristic of therapy-resistant asthma is eosinophil elevation. It is important to better understand the burden of care gaps in this patient subgroup in order to support improved treatment strategies in the future. OBJECTIVE: To quantify the economic burden of asthma patients with and without peripheral blood eosinophil elevation. METHODS: A retrospective cohort study was conducted using data from patients aged 12 years or older with a diagnosis of asthma using electronic health records of over 2 million patients between 2004-2010. Patients with a diagnosis of chronic obstructive pulmonary disease, Churg Strauss syndrome/Wegener's granulomatosis, eosinophilia, cystic/pulmonary fibrosis, allergic bronchopulmonary aspergillosis, or lung cancer in the 12-month period before the date of asthma diagnosis were excluded. Patients with asthma were followed for 12 months after their initial asthma diagnosis to identify those with controlled versus uncontrolled asthma based on ERS/ATS criteria. Patients with at least 1 peripheral blood eosinophil test result of ≥ 400 cells/µL were classified as those with elevated eosinophils. Total annual paid-claim cost was compared by eosinophil levels within the controlled and uncontrolled asthma subgroups. Costs were adjusted to 2015 U.S. dollars. Patients were stratified by control level, and generalized linear modeling regressions were used to assess the magnitude of increase in cost of the elevated eosinophil group. RESULTS: A total of 2,701 patients were included in the study, of which 17% had uncontrolled asthma and 21% had elevated eosinophils. The mean total annual cost of patients with uncontrolled asthma was more than 2 times the cost of those with controlled asthma ($18,341 vs. $8,670, P < 0.001). Patients with uncontrolled asthma in the elevated eosinophil group had almost double the total cost ($28,644 vs. $14,188, P = 0.008) compared with those with blood eosinophil levels in a normal range. Similarly, patients classified as those with controlled asthma in the elevated eosinophil group had almost twice the average costs as those without elevated eosinophils ($14,754 vs. $7,203, P < 0.001). Uncontrolled asthma with elevated eosinophils had 4 times greater hospital admissions and over 4 times higher total costs than controlled asthma without elevated eosinophils. Among patients with uncontrolled asthma, patients with elevated eosinophils had a 53% increase in mean cost ($17,723 vs. $11,581, P < 0.001) compared with patients without elevated eosinophils. Among patients with controlled asthma, patients with elevated eosinophils had a 62% increase in mean cost ($8,897 vs. $5,486, P < 0.001) compared with patients without elevated eosinophils. CONCLUSIONS: Elevated peripheral blood eosinophil level is associated with higher cost irrespective of disease control status. DISCLOSURES: This study was funded by Teva Pharmaceuticals. Dotiwala and Casciano report consulting and writing fees from Teva Pharmaceuticals for work on this study. Sun is an employee and stockholder of Teva Pharmaceuticals. Li reports consulting fees from eMAX Health. All authors contributed to study design. Dotiwala took the lead in data collection, along with the other authors, and data interpretation was performed primarily by Krishnan, Sun, and Li, along with Casciano and Dotiwala. The manuscript was written by Casciano, Dotiwala, and Li, along with Sun and Krishnan, and revised by Casciano, Dotiwala, Sun, and Li, with assistance from Krishnan.

Predictive value of the eosinophil counts in the biological diagnosis of lymphatic filariasis in French Polynesia.

SETTINGS: Lymphatic filariasis is common in many tropical and subtropical areas and is a major public health issue in south Pacific islands. In endemic areas, most infected individuals are asymptomatic but may harbor microfilariae or filarial antigens in their peripheral blood. Microscopy remains the reference diagnostic tool for the identification of microfilariae but is weakly sensitive. The diagnosis of Wuchereria bancrofti infection was dramatically altered by the development of filarial antigen tests, which are easy to perform but expensive for routine use. Lymphatic filariasis is responsible for acquired eosinophilia and blood eosinophil count is commonly used as a screening tool in endemic areas. METHOD: We retrospectively analyzed all the results of eosinophil counts, antigen and microfilariae detection performed in our laboratory over a 24-month period. We calculated the prevalence of antigenemia for various eosinophilic cut offs. RESULTS: The prevalence of antigenemia was estimated at 25.78% with eosinophilia defined as a count eosinophilic PMN above 500 per mm(3). DISCUSSION: Our prevention strategy against lymphatic filariasis is based on annual mass drug administration, vector control, and systematic treatment of antigenemic and microfilaremic patients. Antigenemic and microfilaremic detection cannot be routinely performed because of their cost. Current treatments used for lymphatic filariasis are safe and cheaper than antigenic detection. A possible additional strategy to decrease the prevalence of antigenemia would be the systematic treatment of patients with hypereosinophilia.

Reducing costs in flow-cytometric counting of residual white blood cells in blood products: utilization of a single-platform bead-free flow-rate calibration method.

BACKGROUND: Commercial flow-cytometric methods for counting residual white blood cells (rWBCs) in leukoreduced blood products use calibration beads for estimation of the measured sample volume. A bead-free flow-rate calibration method is developed and validated. STUDY DESIGN AND METHODS: The analyzed volume was calculated by acquisition time (ACQ). Twenty-nine spiking series of red blood cell (RBC) or platelet (PLT) products were prepared containing levels ranging from 0.08 × 10(6) up to 2048 × 10(6) WBCs/L. Nearly WBC-free triple-leukofiltered RBCs or PLT concentrates (PCs) served as background. Propidium iodide (PI) was used to identify rWBCs. Five RBC series were compared against a commercially available kit (LeukoSure, Beckman Coulter). Routine capabilities were tested on 41 RBC and 92 PC samples of two independent transfusion services. RESULTS: The lower detection limit in RBC was 0.08 × 10(6) rWBCs/L for ACQ and 0.16 for LeukoSure. Criteria for linearity, accuracy, and precision were fulfilled within the range of 0.5 × 10(6) to 512 × 10(6) WBCs/L. For PCs, all these criteria were fulfilled between 0.5 × 10(6) and 32 × 10(6) rWBCs/L (lower detection limit of 0.25) for PI. ACQ and LeukoSure agreed sufficiently (81%) when tested on routine RBCs or PCs. CONCLUSION: A residual WBC count of fewer than 0.5 × 10(6) WBCs/L can be accurately counted using the ACQ approach at a total reagent cost of less than 0.5€ per sample.

Eosinopenia as a marker of mortality and length of stay in patients admitted with exacerbations of chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Blood eosinopenia has long been known as a marker of acute infection, and has recently been shown to be a better predictor of sepsis than CRP in critically ill patients. This study examines the usefulness of eosinopenia (< or = 0.04), for predicting the severity of exacerbations of COPD using inpatient mortality and length of stay as markers of severity. METHODS: Retrospective review of the case-notes of patients admitted with an exacerbation of COPD from March 2007 to April 2008. Patients with radiographic evidence of pneumonia and those having steroids in the previous week were excluded. Data were collected for age, length of stay, pH, WCC and mortality. RESULTS: Sixty-five patients fulfilled the inclusion criteria, 42 with a normal eosinophil count and 23 with eosinopenia. No significant differences were seen between the two groups' age, total WCC and admission pH. However, significant differences were seen in mortality (4/23 (17.4%) vs 1/42 (2.4%), P = 0.049) and length of stay (8 vs 5 days, P = 0.005) when the eosinopenia group compared with those with normal eosinophils. CONCLUSIONS: The eosinophil count might be a useful marker of severity inpatients admitted with an exacerbation of COPD independent of the WCC and pH. As it is routinely given in the full blood count in all patients admitted to hospital, there is no extra cost for this beneficial test.

Is there yet any place for reagent strips in diagnosing spontaneous bacterial peritonitis in cirrhotic patients? An accuracy and cost-effectiveness study in Brazil.

BACKGROUND: Diagnosis of spontaneous bacterial peritonitis (SBP) is currently based on ascitic cell counting, but there is a need for a more simple and rapid diagnostic tool. The objectives of this study are to evaluate the accuracy of reagent strips in diagnosing SBP and compare their costs with total and differential cell counts. PATIENTS AND METHODS: 71 cirrhotic in- and outpatients were consecutively included (159 samples). Spontaneous bacterial peritonitis was defined as neutrophil cells >or= 250/microL. The cutoff values for each reagent strip were defined by a receiver operating characteristic (ROC) curve. Sensitivity (S), Specificity (Sp), Positive and Negative Predictive Values (PPV and NPV), Accuracy (Ac) and cost-effectiveness (US$) in comparison to cell count exam were calculated. RESULTS: Spontaneous bacterial peritonitis was diagnosed in 17 patients (23.9%), 11 of them with positive culture (64.7%). The best cutoff points found in ROC curves were 1+ for Multistix 10 SG and ca. 75 for Choiceline 10 (Multistix 10 SG S = 80%, Sp = 98.5%, PPV = 90.9%, NPV = 96.2%, Ac = 95%; Choiceline 10 S = 76.9%, Sp = 97.7%, PPV = 87%, NPV = 95.6%, Ac = 94%). In terms of cost-effectiveness by cost/accuracy, cell count was 41.5, Multistix 10 SG 0.57, and Choiceline 10, 0.19 (P < 0.001). CONCLUSION: Reagent strips are a useful tool for diagnosing SBP in cirrhotic patients, but they have some limitations. Strips are especially indicated when total and differential cell counts are not quickly available or sometimes unavailable. They are also indicated as screening test in emergency rooms to anticipate the diagnosis of SBP and allow its early treatment. It's an interesting option in developing countries.

Biological diagnosis of meningococcal meningitis in the African meningitis belt: current epidemic strategy and new perspectives.

Laboratory diagnosis is an essential component in surveillance of meningococcal epidemics, as it can inform decision-makers of the Neisseria meningitidis serogroup(s) involved and the most appropriate vaccine to be selected for mass vaccination. However, countries most affected face real limitations in laboratory diagnostics, due to lack of resources. We describe current diagnostic tools and examine their cost-effectiveness for use in an epidemic context. The conclusion is that current WHO recommendations to use only the latex agglutination assay (Pastorex) at epidemic onset is cost-effective, but recently developed rapid diagnostic tests for the major epidemic-causing meningococcal serogroups may prove a breakthrough for the future.

Validation of the Beckman Coulter AcT 5 diff analyzer in a reference laboratory.

At the Valle de Hebron Hospital's Central Laboratory, we have performed a study evaluating the performance, reliability, and practicability of the Beckman Coulter AcT 5 analyzer. The results observed with known controls showed within- and between-run imprecision of 1.05% to 6.97% for the basic hemogram parameters. With patient samples, the results were analogous, with within- and between-run imprecision of 1.33% to 5.98%. To complete the evaluation of the AcT 5 counter, we analyzed the influence of possible interfering factors such as the presence of jaundice, lipemia, hemolysis, platelet aggregates, and schistocytes on the results of the automated leukocyte differential as performed by the cell counter with the new chlorazol black stain. We studied the performance of the AcT 5 with regards to ease of use, speed, and cost. Finally, we evaluated the impact of introducing the AcT 5 counter into routine laboratory use as support to resolve problems raised with the Beckman Coulter GenS and LH-750 and the Bayer Advia 120 counters due to samples with interfering factors.

Comparison of two alternative methods for CD4+ T-cell determination (Coulter manual CD4 count and CyFlow) against standard dual platform flow cytometry in Uganda.

BACKGROUND: In this study we evaluated alternative CD4(+) T-cell counting methods in clients of a PMTCT Programme in rural Uganda. METHODS: The Coulter Manual CD4 Count method for CD4(+) T-cell enumeration (Cyto-Spheres) and an automated method (volumetric, single-platform flow cytometry; CyFlow) were compared with a standard, dual-platform flow cytometry protocol (DPFC, FACScan). RESULTS: Correlation and precision of agreement were higher for the CyFlow method (r = 0.929 and eta = 0.08) when compared to DPFC than for the Cyto-Spheres method (r = 0.725 and eta = 0.3). Multiple linear regression analysis showed that CD4(+) cell counts by the CyFlow method were a stronger predictor for results of DPFC than those of the Cyto-Spheres method (r(2) = 0.864 and r(2) = 0.552, respectively). When compared to DPFC the CyFlow method generated higher CD4(+) cell counts than the Cyto-Spheres method, as expressed by a higher median and mean difference (+70 and +90 cells for CyFlow, +28 and -1.4 cells for Cyto-Spheres). CONCLUSION: Both, the manual Cyto-Spheres method and the CyFlow method can be used for the enumeration of CD4(+) cells in resource-limited settings. Under supervised conditions, the CyFlow method produced results more consistent with the reference method than the Cyto-Spheres method.

Economic consequence of immediate testing for C-reactive protein and leukocyte count in new outpatients with acute infection.

BACKGROUND: There have been few well-designed studies that assess the cost-effectiveness of near-patient immediate testing. METHODS: We analyzed the economic outcome of immediate testing for C-reactive protein (CRP) and white blood cell count (WBC) in 305 new outpatients with acute infections. Patients were randomized into two groups: 147 patients were tested immediately for CRP and WBC before the physician's initial consultation (advance testing), and 154 patients were not subjected to advance testing. The subsequent prescribing decision and the drug/testing/personnel costs were compared between the groups. RESULTS: In the advance-testing group, the initial consultation was followed by a total of 84 prescriptions of oral antibiotics, against 158 in the other group. Comparing the total costs of oral and parenteral antibiotics between the two groups, a 30% reduction was achieved with advance testing ( yen105,830 vs. yen151,102). However, the savings were largely offset by frequent prescription of newer, expensive influenza neuraminidase inhibitors. Advance testing also significantly reduced additional laboratory use. More frequent urgent testing increased personnel costs in the non-advance-testing group. Overall, total cost was somewhat higher in the advance-testing group ( yen1,028,827 vs. yen984,105). CONCLUSIONS: The cost per antibiotic prescription reduced with advance testing was yen604 (approximately 5.8 US dollars) in our clinical setting. Judicious use of antivirals and introduction of a simple CRP test kit would improve cost-effectiveness.

Comparison of the AcT 5 diff autoloader hematology analyzer to the Abbott Cell-Dyn 3200 analyzer at Charlevoix Area Hospital.

The Coulter AcT 5 diff autoloader (AL) hematology analyzer (Beckman Coulter, Fullerton, CA, USA) was evaluated at the Charlevoix Area Hospital, a small rural community hospital. The analyzer was compared to the laboratory's current instrument, a Cell-Dyn 3200 (Abbott Laboratories, Abbott Park, IL, USA). The study included comparisons of precision, efficiency and productivity, and reliability. The 5-part white blood cell differentials on both instruments were compared, and the clinical utility and flagging performance of both analyzers were confirmed by manual differential counts. The AcT 5 diff AL was shown to have excellent precision and accuracy. The addition of the autoloader to the AcT 5 diff provides a low-volume system with the added benefits of a "load and leave" analyzer normally available only to larger laboratories.

Determination of peripheral blood stem cells by the Sysmex SE-9500.

The Sysmex SE-9500 automated haematology analyser provides an estimate of immature cells, referred to as 'haematopoietic progenitor cells' (HPC). The aim of this study was to evaluate the reliability and usefulness of the SE-9500 HPC parameter as compared with the CD34 + cell count and to determine whether the HPC count was of value in predicting the optimal harvesting time for peripheral blood stem cells (PBSC). Studies were performed on 112 samples from 21 patients with haematological malignancies and 13 healthy donors undergoing progenitor cell mobilisation. Coefficients of variation for the HPC count were 30%, 23.8%, 12.4% and 8.3% respectively for samples with low (4 x 106/l), medium (13 x 106/l), high (250 x 106/l) and very high (2413 x 106/l) counts. There was good linearity for HPC measurement in both peripheral blood (PB) and purified CD34 + cell suspensions (r > 0.995), and no detectable carryover was observed. There was an acceptable correlation between HPC and CD34 + cell counts for PB samples (r=0.669) and for CD34 + cell suspensions (r=0.859). Analysis of purified CD34 + cells using the SE-9500 HPC mode revealed that they appear both in the blast cell area and the immature granulocyte area of the analyser cell display. Quantitation of CD34 + cells and HPC during PBSC mobilisation showed good agreement between these parameters with regard to the optimal time for PBSC harvesting. These findings suggest that HPC counting with the Sysmex SE-9500 may be clinically useful for optimising the timing of PBSC collection.

Cost-effectiveness of clozapine monitoring after the first 6 months.

BACKGROUND: Clozapine is effective in treating patients with schizophrenia who do not respond to conventional neuroleptic drugs. The drug is unique in that it is available only with a US Food and Drug Administration-mandated system for weekly monitoring of patients' white blood cell counts. No study has been conducted to evaluate the cost-effectiveness of this mandatory monitoring system. METHODS: A benchmark case was established by utilizing cumulative incidence rates of agranulocytosis from a recent study with a large sample of clozapine-treated patients. We assumed a 20% mortality among patients with agranulocytosis, $30.61 in monitoring costs each week, and 14.4 years of remaining life expectancy after detection of agranulocytosis. Based on these bench-mark assumptions, cost-effectiveness ratios in dollars per quality-adjusted life-year were calculated for the first, second, and third 6-month periods during which a patient was receiving clozapine. Sensitivity analyses were performed with more conservative assumptions in 5 alternative scenarios. RESULTS: In the benchmark case, costs per quality-adjusted life-year gained were $61,694, $925,418, and $420,644 for the first, second, and third 6-month periods of clozapine treatment, respectively. In the alternative scenarios, these costs ranged from $7923 to $46,056 for the first 6-month period and from $54,025 to $690,850 for the second and third 6-month periods. CONCLUSIONS: While the costs of monitoring patients with schizophrenia in the first 6-month period of clozapine treatment seem to be justifiable, monitoring thereafter may not be cost-effective because of the very low incidence of agranulocytosis in the later periods.