Exploring the potential harm of varied blood storage on patients undergoing cardiovascular surgery.

BACKGROUND AND OBJECTIVES: Debate exists surrounding the optimal duration of red blood cell (RBC) storage. A hypothesis emerging from previous research suggests that exposure to fresh blood may be harmful to patients undergoing cardiac surgery. This study uses a large transfusion medicine database to explore the association between in-hospital mortality and red cell storage duration. MATERIALS AND METHODS: This is an exploratory retrospective cohort study of all adult patients at Hamilton, Canada, over a 14-year period that received at least one allogeneic red cell transfusion during their hospitalization for cardiac surgery requiring bypass. The primary outcome for the study was in-hospital death. Analysis was performed using multivariate Cox regression modelling with time-dependent and time-independent covariates and stratification variables. Five models with varying definitions for short, intermediate and prolonged duration of RBC storage were tested. RESULTS: From March 2004 to December 2017, 11,205 patients met the inclusion criteria and were included in the regression analyses. No significant effect of short-duration red storage on patient mortality was observed in all statistical models, with the red cells stored for the longest duration as the reference group. When patients who received exclusively fresh (hazard ratio [HR] 1.040, 95% confidence interval [CI] 0.588-1.841, p-value = 0.893) and older aged (HR 1.038, 95% CI 0.769-1.1.402, p-value = 0.0801) RBCs were compared with those who received exclusively mid-age red cells as the reference, statistical significance was similarly not reached. CONCLUSION: Red cells stored for the shortest duration are not associated with increased risk of mortality among cardiac surgery patients.

An evaluation of the clinical impacts of 7-day platelets.

BACKGROUND: In August 2017, Canadian Blood Services extended the shelf-life of platelet concentrates from 5 to 7 days. The clinical impacts of this policy change remain unclear. STUDY DESIGN AND METHODS: We used a before-after retrospective design of platelet-transfused adult inpatients in Hamilton, ON, Canada. Data were captured for 18 months before (Period 1: February 2016-July 2017) and 18 months after (Period 2: September 2017-February 2019) 7-day platelet implementation. Primary outcome was absolute platelet count increment (ACI) in univariate and multivariate analyses adjusted for confounders. Data were obtained from our institution's transfusion database, Ontario's Transfusion Transmitted Injuries Surveillance System, and the blood supplier. RESULTS: Overall, 1360 patients with single dose platelet transfusions were included in Period 1 and 1211 patients in Period 2. Median age at admission was 66 years, and approximately 40% of patients underwent cardiac surgery. Using a non-inferiority margin of -10 × 109 /L, platelets transfused during the 7-day storage period were non-inferior to those transfused in the 5-day storage period [mean count difference - 4.63 × 109 /L (95% CI -7.40 to -1.87, p = 0.0001)]. However, platelet ACIs following transfusion consistently trended lower in the 7-day group for all patients and subgroups. No differences in secondary clinical outcomes were observed. Platelet expiry reduced from 8.1 to 6.3% (p < 0.0001). CONCLUSION: Platelet transfusions following 7-day storage policy were non-inferior to transfusions in the 5-day policy period, although reduced ACIs were observed. There were no increases in adverse clinical outcomes.

Prevalence and significance of large granular lymphocytes in patients with immune thrombocytopenia.

The association between T-cell large granular lymphocytes (T-LGL) and ITP is uncertain. The aims of this study were to determine the prevalence of T-LGL in patients with ITP and to describe its association with ITP disease severity. We analyzed flow cytometry results for T-LGL (using a threshold of 0.3 x109 or greater cells/L) or positive T-cell receptor clonality in patients with ITP and nonimmune thrombocytopenia. Descriptive statistics were used to characterize the association between T-LGL and ITP, response to ITP treatments (rituximab and splenectomy) and response to T-LGL treatment. Among ITP patients, 14.3% (13/91) had evidence of a T-LGL population compared to 10.3% (3/29) of patients with non-immune thrombocytopenia. ITP patients with T-LGL had lower nadir platelet counts (2 vs. 47 × 109/L) and received more ITP treatments (median 6 vs. 3) than ITP patients without T-LGL. Response to rituximab was observed in 14.3% (1/7) of ITP patients with T-LGL and 54.5% (6/11) without T-LGL. Response to splenectomy was observed in 25% (2/8) with T-LGL and 56.2% (9/16) without T-LGL. Four patients with ITP and T-LGL received treatment for T-LGL with methotrexate; none had an improvement in platelet count levels. T-LGL may appear in patients with ITP, and the meaning of this finding remains unclear; however, for some patients, the presence of abnormal T-LGL may indicate a more severe form of ITP that tends to be less responsive to therapy. In this cohort, treatment of T-LGL with methotrexate did not improve platelet counts in the few patients who were treated.

Accuracy of International Classification of Diseases, 10th Revision Codes for Identifying Sepsis: A Systematic Review and Meta-Analysis.

Administrative databases are increasingly used in research studies to capture clinical outcomes such as sepsis. This systematic review and meta-analysis examines the accuracy of International Classification of Diseases, 10th revision (ICD-10), codes for identifying sepsis in adult and pediatric patients. DATA SOURCES: We searched MEDLINE, EMBASE, Web of Science, CENTRAL, Epistemonikos, and McMaster Superfilters from inception to September 7, 2021. STUDY SELECTION: We included studies that validated the accuracy of sepsis ICD-10 codes against any reference standard. DATA EXTRACTION: Three authors, working in duplicate, independently extracted data. We conducted meta-analysis using a random effects model to pool sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We evaluated individual study risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool and assessed certainty in pooled diagnostic effect measures using the Grading of Recommendations Assessment, Development, and Evaluation framework. DATA SYNTHESIS: Thirteen eligible studies were included in the qualitative synthesis and the meta-analysis. Eleven studies used manual chart review as the reference standard, and four studies used registry databases. Only one study evaluated pediatric patients exclusively. Compared with the reference standard of detailed chart review and/or registry databases, the pooled sensitivity for sepsis ICD-10 codes was 35% (95% CI, 22-48, low certainty), whereas the pooled specificity was 98% (95% CI: 98-99, low certainty). The PPV for ICD-10 codes ranged from 9.8% to 100% (median, 72.0%; interquartile range [IQR], 50.0-84.7%). NPV ranged from 54.7% to 99.1% (median, 95.9%; interquartile range, 85.5-98.3%). CONCLUSIONS: Sepsis is undercoded in administrative databases. Future research is needed to explore if greater consistency in ICD-10 code definitions and enhanced quality measures for ICD-10 coders can improve the coding accuracy of sepsis in large databases.

Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial.

BACKGROUND: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection. METHODS: CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600). DISCUSSION: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification. TRIAL REGISTRATION: Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.

"Is there anything good about a water advisory?": an exploration of the consequences of drinking water advisories in an indigenous community.

BACKGROUND: In Ontario, Canada, Indigenous communities experience some of the province's worst drinking water, with issues ranging from deteriorating water quality to regulatory problems and lack of support. When water is known, or suspected, to be unsafe for human consumption, communities are placed under a Drinking Water Advisory. Between 2004 and 2013, approximately 70% of all on-reserve communities in Ontario were under at least one Drinking Water Advisory. Despite the widespread impact of Drinking Water Advisories on health and wellbeing, little is known about First Nation individuals' perceptions and experiences living with a Drinking Water Advisory. This study presents information shared by members of a community who have lived with Boil Water Advisories on and off for many years, and a long-term Boil Water Advisory since 2017. The goal of this paper is to unpack and explore the Boil Water Advisories from the perspective of community members and provide considerations for current and future Boil Water Advisory management. METHODS: Methodological choices were driven by the principles of community-based participatory research. Two data collection methodologies were employed: hard copy surveys and interviews. RESULTS: Forty-four individuals (19.5%) completed a survey. Eight Elders and 16 key informants participated in 20 interviews. Respondents expressed varying degrees of uncertainty regarding protective actions to take while under a Boil Water Advisory. Further, 79% of men but only 46% of women indicated they always adhere to the Boil Water Advisory. Knowledge gaps that could lead to risky behaviours were also identified. Finally, Boil Water Advisories were demonstrated to have physical, financial, and time impacts on the majority of respondents. CONCLUSIONS: A direct outcome was the identification of a critical need to reinforce best practices for health protection through community education and outreach. More broadly, Chief and Council were able to use the findings to successfully advocate for improved drinking water for the community. Additionally, benefits of participatory research and community ownership include enhanced local research capacity, and increased awareness of, and desire for, research to inform decisions.