Blood donor, component, and recipient-specific factors associated with venous thromboembolism in transfused hospitalized adult patients: Data from the recipient epidemiology and donor evaluation Study-III (REDS-III).

OBJECTIVE: Growing evidence suggests multiple pathophysiological mechanisms linking red blood cells (RBC) transfusions to thrombosis. This study examined blood donor, component, and recipient factors which may be associated with thromboembolic outcomes following RBC transfusion. METHODS: We utilized the Recipient Epidemiology Donor Evaluation Study-III (REDS-III) database on patients transfused in 12 hospitals between 2013-2016. Stratified Cox proportional hazards regression models with time-dependent exposures were used to examine associations of donor and component modification characteristics on venous thromboembolism (VTE) in patients transfused RBC units. RESULTS: 59,603 patients were transfused 229,500 RBC units during 79,298 hospitalizations with post-transfusion VTE occurring in 1869 (2.4%) of patients. In adjusted regression analyses, a per RBC-unit risk of VTE was present for gamma irradiation (HR = 1.03; 95% CI: 1.02-1.03), female donor sex (HR = 1.01; 95% CI: 1.00-1.01), storage duration greater than 5 weeks (HR = 1.01; 95% CI: 1.01-1.02), AS-1 storage solution (HR = 1.01; 95% CI: 1.00-1.01), and apheresis-derived collections (HR = 1.01; 95% CI: 1.01-1.02). Among recipient factors, male sex (HR = 1.03; 95% CI: 1.02-1.04), pre-transfusion hemoglobin level (HR = 0.94; 95% CI: 0.94-0.94), body mass index strata (HR = 1.11; 95% CI: 1.08-1.14), and principal diagnoses including malignancy (HR = 1.13; 95% CI: 1.10-1.16), cardiac arrest (HR = 1.38; 95% CI:1.07-1.77) and hip fracture (HR = 1.59; 95% CI:1.53-1.66) were associated with VTE in adjusted analyses. DISCUSSION: We identified several donor, component, and recipient-specific factors associated with VTE in transfused hospitalized adult patients. In adjusted models, the dose-dependent associations of donor and component-specific factors with VTE were modest and unlikely to be clinically significant in the majority of transfused patients. Additional mechanistic and clinical studies linking blood donor and component factors with thrombotic outcomes are needed.

Associations of donor, component, and recipient factors on hemoglobin increments following red blood cell transfusion in very low birth weight infants.

BACKGROUND: Anemia in very low birth weight (VLBW) infants is common and frequently managed with red blood cell (RBC) transfusions. We utilized a linked vein-to-vein database to assess the role of blood donors and component factors on measures of RBC transfusion effectiveness in VLBW infants. STUDY DESIGN AND METHODS: We linked blood donor and component manufacturing data with VLBW infants transfused RBCs between January 1, 2013 and December 31, 2016 in the Recipient Epidemiology Donor Evaluation Study-III (REDS III) database. Using multivariable regression, hemoglobin increments and subsequent transfusion events following single-unit RBC transfusion episodes were examined with consideration of donor, component, and recipient factors. RESULTS: Data on VLBW infants (n = 254) who received one or more single-unit RBC transfusions (n = 567 units) were linked to donor demographic and component manufacturing characteristics for analysis. Reduced post-transfusion hemoglobin increments were associated with RBC units donated by female donors (-0.24 g/dL [95% confidence interval (CI) -0.57, -0.02]; p = .04) and donors <25 years old (-0.57 g/dL [95% CI -1.02, -0.11]; p = .02). For RBC units donated by male donors, reduced donor hemoglobin levels were associated with an increased need for subsequent recipient RBC transfusion (odds ratio 3.0 [95% CI 1.3, 6.7]; p < .01). In contrast, component characteristics, storage duration, and time from irradiation to transfusion were not associated with post-transfusion hemoglobin increments. CONCLUSION: Donor sex, age, and hemoglobin levels were associated with measures of RBC transfusion effectiveness in VLBW infants. Mechanistic studies are needed to better understand the role of these potential donor factors on other clinical outcomes in VLBW infants.

Effect of donor, component, and recipient characteristics on hemoglobin increments following red blood cell transfusion.

Significant research has focused individually on blood donors, product preparation and storage, and optimal transfusion practice. To better understand the interplay between these factors on measures of red blood cell (RBC) transfusion efficacy, we conducted a linked analysis of blood donor and component data with patients who received single-unit RBC transfusions between 2008 and 2016. Hemoglobin levels before and after RBC transfusions and at 24- and 48-hour intervals after transfusion were analyzed. Generalized estimating equation linear regression models were fit to examine hemoglobin increments after RBC transfusion adjusting for donor and recipient demographic characteristics, collection method, additive solution, gamma irradiation, and storage duration. We linked data on 23 194 transfusion recipients who received one or more single-unit RBC transfusions (n = 38 019 units) to donor demographic and component characteristics. Donor and recipient sex, Rh-D status, collection method, gamma irradiation, recipient age and body mass index, and pretransfusion hemoglobin levels were significant predictors of hemoglobin increments in univariate and multivariable analyses (P < .01). For hemoglobin increments 24 hours after transfusion, the coefficient of determination for the generalized estimating equation models was 0.25, with an estimated correlation between actual and predicted values of 0.5. Collectively, blood donor demographic characteristics, collection and processing methods, and recipient characteristics accounted for significant variation in hemoglobin increments related to RBC transfusion. Multivariable modeling allows the prediction of changes in hemoglobin using donor-, component-, and patient-level characteristics. Accounting for these factors will be critical for future analyses of donor and component factors, including genetic polymorphisms, on posttransfusion increments and other patient outcomes.

Additive effects of blood donor smoking and gamma irradiation on outcome measures of red blood cell transfusion.

BACKGROUND: Recent publications have reported conflicting results regarding the role of blood donor tobacco use on hemoglobin (Hb) levels in patients after red blood cell (RBC) transfusion. We examined associations and interactions between donor, component, and recipient factors to better understand the impact of donor smoking on transfusion outcomes. STUDY DESIGN AND METHODS: We linked blood donor and component manufacturing data, including self-reported cigarette smoking, with a cohort of patients transfused RBCs between 2013 and 2016. Using multivariable regression, we examined Hb increments and subsequent transfusion requirements after single-unit RBC transfusion episodes, adjusting for donor, component, and recipient factors. RESULTS: We linked data on 4038 transfusion recipients who received one or more single-unit RBC transfusions (n = 5086 units) to donor demographic and component manufacturing characteristics. Among RBC units from smokers (n = 326), Hb increments were reduced after transfusion of gamma-irradiated units (0.76 g/dL; p = 0.033) but not unirradiated units (1.04 g/dL; p = 0.54) compared to those from nonsmokers (1.01 g/dL; n = 4760). In parallel with changes in Hb levels, donor smoking was associated with the receipt of additional RBC transfusions for irradiated (odds ratio [OR], 2.49; p = 0.01) but not unirradiated RBC units (OR, 1.10; p = 0.52). CONCLUSION: Donor smoking was associated with reduced Hb increments and the need for additional transfusions in recipients of gamma-irradiated RBC units. Additional research is needed to better understand interactions between donor, component, and recipient factors on efficacy measures of RBC transfusion.

Red blood cell transfusions for emergency department patients with gastrointestinal bleeding within an integrated health system.

STUDY OBJECTIVE: To assess trends over time in red blood cell (RBC) transfusion practice among emergency department (ED) patients with gastrointestinal (GI) bleeding within an integrated healthcare system, inclusive of 21 EDs. METHODS: Retrospective cohort of ED patients diagnosed with GI bleeding between July 1st, 2012 and September 30th, 2016. The primary outcome was receipt of an RBC transfusion in the ED. Secondary outcomes included 90-day rates of RBC transfusion, repeat ED visits, rehospitalization, and all-cause mortality. Logistic regression was used to obtain confounder-adjusted outcome rates. RESULTS: A total of 24,868 unique patient encounters were used for the primary analysis. The median hemoglobin level in the ED prior to RBC transfusion decreased from 7.5 g/dl to 6.9 g/dl in the first versus last twelve months of the study period (p < 0.0001). A small trend was observed in the overall adjusted rate of ED RBC transfusion (absolute quarterly change of -0.1%, R2 = 0.18, p = 0.0001) largely attributable to the subgroup of patients with hemoglobin nadirs between 7.0 and 9.9 g/dl (absolute quarterly change of -0.4%, R2 = 0.38, p < 0.0001). Rates of RBC transfusions through 90 days likewise decreased (absolute quarterly change of -0.4%, R2 = 0.85, p < 0.0001) with stable to decreased corresponding rates of repeat ED visits, rehospitalizations and mortality. CONCLUSION: Rates of ED RBC transfusion decreased over time among patients with GI bleeding, particularly in those with hemoglobin nadirs between 7.0 and 9.9 g/dl. These findings suggest that ED providers are willing to adopt evidence-based restrictive RBC transfusion recommendations for patients with GI bleeding.

Donor genetic and nongenetic factors affecting red blood cell transfusion effectiveness.

BACKGROUNDRBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness.METHODSThis is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness.RESULTSBlood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, γ irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor G6PD deficiency and polymorphisms in SEC14L4, HBA2, and MYO9B genes were associated with decreased hemoglobin increments. Donor G6PD deficiency and polymorphisms in SEC14L4 were associated with increased transfusion requirements in the subsequent 48 hours.CONCLUSIONDonor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products.FUNDINGFunding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).

Evaluation of an intervention targeted with predictive analytics to prevent readmissions in an integrated health system: observational study.

OBJECTIVES: To determine the associations between a care coordination intervention (the Transitions Program) targeted to patients after hospital discharge and 30 day readmission and mortality in a large, integrated healthcare system. DESIGN: Observational study. SETTING: 21 hospitals operated by Kaiser Permanente Northern California. PARTICIPANTS: 1 539 285 eligible index hospital admissions corresponding to 739 040 unique patients from June 2010 to December 2018. 411 507 patients were discharged post-implementation of the Transitions Program; 80 424 (19.5%) of these patients were at medium or high predicted risk and were assigned to receive the intervention after discharge. INTERVENTION: Patients admitted to hospital were automatically assigned to be followed by the Transitions Program in the 30 days post-discharge if their predicted risk of 30 day readmission or mortality was greater than 25% on the basis of electronic health record data. MAIN OUTCOME MEASURES: Non-elective hospital readmissions and all cause mortality in the 30 days after hospital discharge. RESULTS: Difference-in-differences estimates indicated that the intervention was associated with significantly reduced odds of 30 day non-elective readmission (adjusted odds ratio 0.91, 95% confidence interval 0.89 to 0.93; absolute risk reduction 95% confidence interval -2.5%, -3.1% to -2.0%) but not with the odds of 30 day post-discharge mortality (1.00, 0.95 to 1.04). Based on the regression discontinuity estimate, the association with readmission was of similar magnitude (absolute risk reduction -2.7%, -3.2% to -2.2%) among patients at medium risk near the risk threshold used for enrollment. However, the regression discontinuity estimate of the association with post-discharge mortality (-0.7% -1.4% to -0.0%) was significant and suggested benefit in this subgroup of patients. CONCLUSIONS: In an integrated health system, the implementation of a comprehensive readmissions prevention intervention was associated with a reduction in 30 day readmission rates. Moreover, there was no association with 30 day post-discharge mortality, except among medium risk patients, where some evidence for benefit was found. Altogether, the study provides evidence to suggest the effectiveness of readmission prevention interventions in community settings, but further research might be required to confirm the findings beyond this setting.

Community-level obesity prevention is not associated with dieting behaviours and weight dissatisfaction in children: The Healthy Communities Study.

BACKGROUND: Within the context of high childhood obesity prevalence, there is a concern that community efforts intended to reduce childhood obesity may lead to unintended adverse outcomes. OBJECTIVE: This analysis examined relationships between community programs, policies, and environmental changes (CPPs) for obesity prevention with unhealthy dieting behaviours and body weight satisfaction in children. METHODS: Using the Healthy Communities Study 2013 to 2015 survey sample of 5138 US children aged 4 to 15 years old, multilevel models examined associations between standardized CPP intensity scores and child dieting behaviours and weight satisfaction, adjusting for community and child-level covariates and clustered study design. RESULTS: In fully adjusted models, higher total, physical activity, and nutrition CPP intensity scores were associated with lower odds of dissatisfaction with weight (1 year total CPP odds ratio [OR]: 0.41, 95% confidence interval [CI], 0.22-0.73; 6 year total CPP OR: 0.48, 0.29-0.80). Higher physical activity CPP intensity over the past year was associated with greater odds of weight satisfaction (OR: 1.77, 95% CI, 1.10-2.84). No associations were observed with dieting behaviours. CONCLUSIONS: Results suggest that community efforts focusing on nutrition and physical activity to prevent childhood obesity may be associated with weight satisfaction and not with unhealthy dieting behaviours.

Multiyear Rehospitalization Rates and Hospital Outcomes in an Integrated Health Care System.

Importance: Since the introduction of the rehospitalization rate as a quality measure, multiple changes have taken place in the US health care delivery system. Interpreting rehospitalization rates without taking a global view of these changes and new data elements from comprehensive electronic medical records yields a limited assessment of the quality of care. Objective: To examine hospitalization outcomes from a broad perspective, including the implications of numerator and denominator definitions, all adult patients with all diagnoses, and detailed clinical data. Design, Setting, and Participants: This cohort study obtained data from 21 hospitals in Kaiser Permanente Northern California (KPNC), an integrated health care delivery system that serves patients with Medicare Advantage plans, Medicaid, and/or Kaiser Foundation Health Plan. The KPNC electronic medical record system was used to capture hospitalization data for adult patients who were 18 years of age or older; discharged from June 1, 2010, through December 31, 2017; and hospitalized for reasons other than childbirth. Hospital stays for transferred patients were linked using public and internal sources. Exposures: Hospitalization type (inpatient, for observation only), comorbidity burden, acute physiology score, and care directives. Main Outcomes and Measures: Mortality (inpatient, 30-day, and 30-day postdischarge), nonelective rehospitalization, and discharge disposition (home, home with home health assistance, regular skilled nursing facility, or custodial skilled nursing facility). Results: In total, 1 384 025 hospitalizations were identified, of which 1 155 034 (83.5%) were inpatient and 228 991 (16.5%) were for observation only. These hospitalizations involved 679 831 patients (mean [SD] age, 61.4 [18.1] years; 362 582 female [53.3%]). The number of for-observation-only hospitalizations increased from 16 497 (9.4%) in the first year of the study to 120 215 (20.5%) in the last period of the study, whereas inpatient hospitalizations with length of stay less than 24 hours decreased by 33% (from 12 008 [6.9%] to 27 108 [4.6%]). Illness burden measured using administrative data or acute physiology score increased significantly. The proportion of patients with a Comorbidity Point Score of 65 or higher increased from 20.5% (range across hospitals, 18.4%-26.4%) to 28.8% (range, 22.3%-33.0%), as did the proportion with a Charlson Comorbidity Index score of 4 or higher, which increased from 28.8% (range, 24.6%-35.0%) to 38.4% (range, 31.9%-43.4%). The proportion of patients at or near critical illness (Laboratory-based Acute Physiology Score [LAPS2] ≥110) increased by 21.4% (10.3% [range across hospitals, 7.4%-14.7%] to 12.5% [range across hospitals, 8.3%-16.6%]; P < .001), reflecting a steady increase of 0.07 (95% CI, 0.04-0.10) LAPS2 points per month. Unadjusted inpatient mortality in the first year of the study was 2.78% and in the last year was 2.71%; the corresponding numbers for 30-day mortality were 5.88% and 6.15%, for 30-day postdischarge mortality were 3.94% and 4.22%, and for nonelective rehospitalization were 12.00% and 12.81%, respectively. All outcomes improved after risk adjustment. Compared with the first month, the final observed to expected ratio was 0.79 (95% CI, 0.73-0.84) for inpatient mortality, 0.86 (95% CI, 0.82-0.89) for 30-day mortality, 0.90 (95% CI, 0.85-0.95) for 30-day nonelective rehospitalization, and 0.87 (95% CI, 0.83-0.92) for 30-day postdischarge mortality. The proportion of nonelective rehospitalizations meeting public reporting criteria decreased substantially over the study period (from 58.0% in 2010-2011 to 45.2% in 2017); most of this decrease was associated with the exclusion of observation stays. Conclusions and Relevance: This study found that in this integrated system, the hospitalization rate decreased and risk-adjusted hospital outcomes improved steadily over the 7.5-year study period despite worsening case mix. The comprehensive results suggest that future assessments of care quality should consider the implications of numerator and denominator definitions, display multiple metrics concurrently, and include all hospitalization types and detailed data.

Trends in Outpatient Visits and Hospital and Intensive Care Unit Admissions of Adults With COVID-19 in an Integrated US Health Care System, March 2020 to January 2022.

This cohort study of patients at a single integrated health system examines trends in COVID-19­related treatment location and mortality.