A protocol for a randomised clinical trial of the effect of providing feedback on inhaler technique and adherence from an electronic device in patients with poorly controlled severe asthma.

INTRODUCTION: In clinical practice, it is difficult to distinguish between patients with refractory asthma from those with poorly controlled asthma, where symptoms persist due to poor adherence, inadequate inhaler technique or comorbid diseases. We designed an audio recording device which, when attached to an inhaler, objectively identifies the time and technique of inhaler use, thereby assessing both aspects of adherence. This study will test the hypothesis that feedback on these two aspects of adherence when passed on to patients improves adherence and helps clinicians distinguish refractory from difficult-to-control asthma. METHODS: This is a single, blind, prospective, randomised, clinical trial performed at 5 research centres. Patients with partially controlled or uncontrolled severe asthma who have also had at least one severe asthma exacerbation in the prior year are eligible to participate. The effect of two types of nurse-delivered education interventions to promote adherence and inhaler technique will be assessed. The active group will receive feedback on their inhaler technique and adherence from the new device over a 3-month period. The control group will also receive training in inhaler technique and strategies to promote adherence, but no feedback from the device. The primary outcome is the difference in actual adherence, a measure that incorporates time and technique of inhaler use between groups at the end of the third month. Secondary outcomes include the number of patients who remain refractory despite good adherence, and differences in the components of adherence after the intervention. Data will be analysed on an intention-to-treat and a per-protocol basis. The sample size is 220 subjects (110 in each group), and loss to follow-up is estimated at 10% which will allow results to show a 10% difference (0.8 power) in adherence between group means with a type I error probability of 0.05. TRIAL REGISTRATION NUMBER: NCT01529697; Pre-results

Addressing Inpatient Glycaemic Control with an Inpatient Glucometry Alert System

Background. Poor inpatient glycaemic control has a prevalence exceeding 30% and results in increased length of stay and higher rates of hospital complications and inpatient mortality. The aim of this study was to improve inpatient glycaemic control by developing an alert system to process point-of-care blood glucose (POC-BG) results. Methods. Microsoft Excel Macros were developed for the processing of daily glucometry data downloaded from the Cobas IT database. Alerts were generated according to ward location for any value less than 4 mmol/L (hypoglycaemia) or greater than 15 mmol/L (moderate-severe hyperglycaemia). The Diabetes Team provided a weekday consult service for patients flagged on the daily reports. This system was implemented for a 60-day period. Results. There was a statistically significant 20% reduction in the percentage of hyperglycaemic patient-day weighted values >15 mmol/L compared to the preimplementation period without a significant change in the percentage of hypoglycaemic values. The time-to-next-reading after a dysglycaemic POC-BG result was reduced by 14% and the time-to-normalization of a dysglycaemic result was reduced from 10.2 hours to 8.4 hours. Conclusion. The alert system reduced the percentage of hyperglycaemic patient-day weighted glucose values and the time-to-normalization of blood glucose

Artificial Intelligence Enhances Diagnostic Flow Cytometry Workflow in the Detection of Minimal Residual Disease of Chronic Lymphocytic Leukemia

Flow cytometric (FC) immunophenotyping is critical but time-consuming in diagnosing minimal residual disease (MRD). We evaluated whether human-in-the-loop artificial intelligence (AI) could improve the efficiency of clinical laboratories in detecting MRD in chronic lymphocytic leukemia (CLL). We developed deep neural networks (DNN) that were trained on a 10-color CLL MRD panel from treated CLL patients, including DNN trained on the full cohort of 202 patients (F-DNN) and DNN trained on 138 patients with low-event cases (MRD < 1000 events) (L-DNN). A hybrid DNN approach was utilized, with F-DNN and L-DNN applied sequentially to cases. “Ground truth” classification of CLL MRD was confirmed by expert analysis. The hybrid DNN approach demonstrated an overall accuracy of 97.1% (95% CI: 84.7–99.9%) in an independent cohort of 34 unknown samples. When CLL cells were reported as a percentage of total white blood cells, there was excellent correlation between the DNN and expert analysis [r > 0.999; Passing–Bablok slope = 0.997 (95% CI: 0.988–0.999) and intercept = 0.001 (95% CI: 0.000–0.001)]. Gating time was dramatically reduced to 12 s/case by DNN from 15 min/case by the manual process. The proposed DNN demonstrated high accuracy in CLL MRD detection and significantly improved workflow efficiency. Additional clinical validation is needed before it can be fully integrated into the existing clinical laboratory practice

Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry

Abstract The diagnosis of leukemic T-cell malignancies is often challenging, due to overlapping features with reactive T-cells and limitations of currently available T-cell clonality assays. Recently developed therapeutic antibodies specific for the mutually exclusive T-cell receptor constant β chain (TRBC)1 and TRBC2 isoforms provide a unique opportunity to assess for TRBC-restriction as a surrogate of clonality in the flow cytometric analysis of T-cell neoplasms. To demonstrate the diagnostic utility of this approach, we studied 164 clinical specimens with (60) or without (104) T-cell neoplasia, in addition to 39 blood samples from healthy donors. Dual TRBC1 and TRBC2 expression was studied within a comprehensive T-cell panel, in a fashion similar to the routine evaluation of kappa and lambda immunoglobulin light chains for the detection of clonal B-cells. Polytypic TRBC expression was demonstrated on total, CD4+ and CD8+ T-cells from all healthy donors; and by intracellular staining on benign T-cell precursors. All neoplastic T-cells were TRBC-restricted, except for 8 cases (13%) lacking TRBC expression. T-cell clones of uncertain significance were identified in 17 samples without T-cell malignancy (13%) and accounted for smaller subsets than neoplastic clones (median: 4.7 vs. 69% of lymphocytes, p < 0.0001). Single staining for TRBC1 produced spurious TRBC1-dim subsets in 24 clinical specimens (15%), all of which resolved with dual TRBC1/2 staining. Assessment of TRBC restriction by flow cytometry provides a rapid diagnostic method to detect clonal T-cells, and to accurately determine the targetable TRBC isoform expressed by T-cell malignancies

Transfusion of Uncrossmatched Group O Erythrocyte-containing Products Does Not Interfere with Most ABO Typings

Background: Group O erythrocytes and/or whole blood are used for urgent transfusions in patients of unknown blood type. This study investigated the impact of transfusing increasing numbers of uncrossmatched type O products on the recipient's first in-hospital ABO type. Methods: This was a retrospective cohort study. Results of the first ABO type obtained in adult, non-type O recipients (i.e., types A, B, AB) after receiving at least one unit of uncrossmatched type O erythrocyte-containing product(s) for any bleeding etiology were analyzed along with the number of uncrossmatched type O erythrocyte-containing products administered in the prehospital and/or in hospital setting before the first type and screen sample was drawn. Results: There were 10 institutions that contributed a total of 695 patient records. Among patients who received up to 10 uncrossmatched type O erythrocyte-containing products, the median A antigen agglutination strength in A and AB individuals on forward typing (i.e., testing the recipient's erythrocytes for A and/or B antigens) was the maximum (4+), whereas the median B antigen agglutination strength among B and AB recipients of up to 10 units was 3 to 4+. The median agglutination strength on the reverse type (i.e., testing the recipient's plasma for corresponding anti-A and -B antibodies) was very strong, between 3 and 4+, for recipients of up to 10 units of uncrossmatched erythrocyte-containing products. Overall, the ABO type of 665 of 695 (95.7%; 95% CI, 93.9 to 97.0%) of these patients could be accurately determined on the first type and screen sample obtained after transfusion of uncrossmatched type O erythrocyte-containing products. Conclusions: The transfusion of smaller quantities of uncrossmatched type O erythrocyte-containing products, in particular up to 10 units, does not usually interfere with determining the recipient's ABO type. The early collection of a type and screen sample is important