Publications

OBJECTIVE: The objective of this study was to examine patient experiences with virtual (telephone and video) encounters in primary care and make recommendations to inform the broader adoption of virtual care.

DESIGN: A descriptive qualitative study using semi-structured interviews for data collection.

SETTING: Ontario, Canada.

PARTICIPANTS: Fifty-five primary care patients across Ontario, Canada, who had experienced at least one virtual (telephone or video) encounter with a healthcare provider in primary care, participated in semi-structured individual interviews conducted between 15 January 2021 and 22 March 2021.

RESULTS: With respect to patients' experiences with virtual care appointments, we identified the following seven themes: (1) Enhancing access, (2) Importance of patient-provider relationship, (3) Active communication and attunement, (4) Assuring privacy and confidentiality, (5) Shorter appointments, (6) Asynchronous technologies being underutilised and (7) Strengthening the future of virtual care. Despite the rapid adoption of synchronous virtual care, participants generally reported positive experiences. Virtual care enhanced access to care and was overwhelmingly supported for continued use. While new patient-provider relationships faced challenges, pre-existing, positive relationships thrived. Concerns about the shortness of virtual care appointments were reported.

CONCLUSIONS: Virtual care offers a promising modality for patients to experience care. Moving forward, primary care practices should consider expanding options for asynchronous virtual care, consider the length of virtual care appointments and offer patients greater choice in the modality of their care appointments.

BACKGROUND: Traumatic intracranial hemorrhage (tICH) is a major driver responsible for traumatic brain injury (TBI)-related deaths. Studies have demonstrated an associated survival benefit with plasma administration among patients with tICH. The administration of whole blood (WB), from which plasma is derived, may provide similar or greater benefits. We hypothesize that WB, compared to plasma-based resuscitation, is associated with reduced 30-day mortality among patients presenting with tICH.

DESIGN: This cohort study using the American College of Surgeons Trauma Quality Improvement Program databank from January 1, 2020, and December 31, 2021, included adult trauma patients with tICH presenting to level I and level II US and Canadian civilian trauma centers. We compared WB resuscitation to plasma-based resuscitation within 4 hours of emergency department (ED) arrival. Primary outcome was mortality at 30 days.

RESULTS: Among 9175 patients analyzed, 1238 (14%) received whole blood and 7937 (86%) received plasma-based resuscitation. The overall 30-day mortality was 43%. WB was associated with reduced mortality at 30 days, demonstrating an unadjusted 30% lower risk of mortality (hazard ratio, 0.70; 95%CI, 0.63-0.77; P = <.001) and a 24% lower risk of 30-day mortality after adjusting for confounders (hazard ratio, 0.76; 95% CI, 0.58-0.98; P =.04).

CONCLUSION: In this cohort study, resuscitation with whole blood was associated with lower 30-day mortality compared to plasma-based resuscitation among patients presenting with tICH. These findings highlight WB as a promising therapeutic strategy for tICH, underscoring the need for future prospective studies to validate its clinical effectiveness.

UNLABELLED: Human platelets change over their 7-10 day lifespan, yet the molecular mechanisms underlying platelet aging remain poorly defined. Using two independent RNA sequencing datasets of fluorescence-activated cell sorted young and old human platelets, we developed a unified transcriptomic model to characterize RNA metabolism across the platelet lifespan, which we termed platelet molecular maturation. This was applied to RNA sequencing data from room-temperature stored platelets (up to 7 days) and cold-stored platelets (7, 14, or 21 days). We identified highly concordant aging signatures, including 6,015 shared expressed genes and 2,008 shared differentially expressed genes (DEGs) with strongly correlated fold changes, demonstrating a conserved platelet aging program. Nucleotide-level analyses revealed preferential 3'-directed degradation among downregulated transcripts during endogenous platelet aging and room-temperature storage, supporting an organized RNA decay process that was correlated with platelet function changes. Room-temperature storage recapitulated platelet molecular maturation, showing concordance with aging-related gene expression changes and enrichment of downregulated gene sets. In contrast, cold-storage significantly attenuated platelet molecular maturation and 3'-directed degradation. A total of 669 genes were consistently differentially expressed between room-temperature and cold-stored platelets, while no DEGs were detected during cold-storage, indicating transcriptional stability. Platelet transcript stability in cold-storage correlated with preserved platelet hemostatic function. These findings establish platelet molecular maturation as a conserved, functionally relevant model linking endogenous platelet aging to platelet storage lesions and providing mechanistic insight into preserved platelet hemostatic function in cold-storage. This atlas of platelet RNA metabolism supports biomarker discovery and strategies to improve storage.

KEY POINTS: By integrating multiple high-quality RNA sequencing datasets with novel analytic approaches tailored to the biology of anucleate platelets, we show that platelet aging is not a passive process of transcript decay, but follows a structured and reproducible molecular trajectory both endogenously and in storage, which we term platelet molecular maturation.Storage temperature emerged as a dominant modifier of this trajectory, with cold-storage markedly slowing RNA metabolic kinetics and preserving transcripts associated with younger, more hemostatically competent platelets.Together, these findings provide mechanistic insight into the platelet storage lesion and identify transcriptomic features that may serve as biomarkers or therapeutic targets to extend platelet shelf life.

Electrical stimulation at cellular resolution to restore the function of neural circuits is limited by the density of available electrode arrays. Although current steering with multi-electrode stimulation can be used to target cells between electrodes, it has not been proven for systematically targeting individual cells. We develop a framework for cellular-resolution current steering, leveraging the biophysics of electrically evoked spike generation, and test its efficacy in isolated macaque and human retina. Currents were passed through three electrodes simultaneously using large-scale high-density microelectrode arrays, directly evoking single spikes in retinal ganglion cells. The currents combined either linearly or nonlinearly to drive spiking, depending on the geometry of the electrodes relative to the cell. These findings were captured by a biophysical model and by a simpler parametric model in which spikes can initiate at several sites on the cell membrane and were leveraged to efficiently identify multi-electrode stimulation patterns that optimized cellular selectivity.

BACKGROUND: Traumatic brain injury (TBI) patients on antiplatelet medications lack definitive treatment for reversal of platelet inhibition and restoration of injury-induced platelet dysfunction. The use of platelet transfusions in this patient population remains controversial. Cold-stored platelets (CSPs) may be hemostatically superior to their room temperature platelet (RTP) counterparts for hemostatic resuscitation, but their impact on post-transfusion platelet function has yet to be assessed clinically. We aimed to evaluate the effect of CSP or RTP on post-transfusion platelet function in TBI patients on antiplatelet medications. We hypothesized that CSP would better restore platelet function based on the extensive in vitro data suggesting hemostatic superiority.

METHODS: We performed a post hoc analysis of a randomized controlled trial comparing CSP and RTP in TBI patients on antiplatelet medications. Platelet hemostatic function was determined pretransfusion and posttransfusion using VerifyNow or thromboelastography with platelet mapping (TEG-PM). Clinical outcomes included 30-day mortality, need for neurosurgical intervention, and follow-up Rotterdam scores.

RESULTS: Of the 94 patients with available data, 49 received CSP and 45 received RTP. Baseline characteristics and pre-transfusion assay measurements were similar between groups. Cold-stored platelet recipients had fewer neurosurgical procedures compared with RTP recipients (4.1% vs. 20.0%, p = 0.016). Room temperature platelet recipients showed a greater increase in TEG-PM kaolin maximum amplitude after transfusion compared with CSP recipients (2.4 mm vs. 0.6 mm, p = 0.004). No other differences were observed between RTP and CSP transfusions.

CONCLUSION: Despite a reduction in neurosurgical events, CSP did not significantly improve observed platelet function in TBI patients on antiplatelet medications. Our findings highlight the disconnect between platelet function assays and clinical results and suggest transfusion of CSP versus RTP has minimal effect on platelet hemostatic function. A definitive trial is needed to assess the efficacy of differentially stored products in the bleeding patient, with consideration placed on how platelet hemostatic function is assessed.

LEVEL OF EVIDENCE: Prognostic/epidemiologic; Level III.

BACKGROUND: Use of low titer group O whole blood (LTOWB) continues to increase in the United States (US). This survey sampled the quality control (QC) practices among the largest blood collectors in the US.

METHODS: A survey on LTOWB collection, QC testing, and distribution was developed and electronically distributed to the chief medical officers of 16 large blood collectors in the US. Only complete survey responses were included.

RESULTS: The response rate was 10/16 (63%) representing approximately 80% of the US blood supply as estimated by the respondents. All of the respondents collected LTOWB from males and 7/10 (70%) also collected from never pregnant females. Eight out of nine (89%) centers that repeat donor anti-A and -B titer testing do so on every donation, with 1/9 (11%) respondent testing previously low titer donors annually. The most common antibody titer threshold that defined low titer was <200 (6/10, 60%). The most common LTOWB collection method was with a platelet-sparing filter in CPD 5/10 (50%). 7/10 (70%) respondents performed QC testing on LTOWB units; all of these respondents collected leukoreduced LTOWB and performed residual leukocyte count testing following leukoreduction. 6/7 (86%) performed residual red blood cell (RBC) recovery counts in the laboratory, 4/7 (57%) measured the unit's weight/volume, while 1/7 (14%) center measured the time taken for leukoreduction. The most often frequency of QC testing was monthly.

CONCLUSION: Current practice at US blood suppliers for QC testing on LTOWB units was limited primarily to testing associated with leukoreduction and RBC counting.

OBJECTIVES: Trauma-induced coagulopathy biomarkers may be influenced by injury mechanism. We sought to identify differences in patterns of coagulopathy with and without severe traumatic brain injury (TBI).

DESIGN: Retrospective cohort study.

SETTING: Harmonized database composed of six major hemorrhagic shock trials: Control of Major Bleeding After Trauma (COMBAT), Cold-stored Platelet Early Intervention in Hemorrhagic Shock (CriSP-HS), Prehospital Air Medical Plasma (PAMPer), Prehospital Whole Blood in Emergency Resuscitation (PPOWER), Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR), and Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport (STAAMP).

PATIENTS: All subjects randomized to placebo or standard-of-care groups with complete data for international normalized ratio (INR), thromboelastography values (alpha angle [AA], K time, maximum amplitude [MA], and lysis in 30 min), and Abbreviated Injury Scores (AISs). Subjects from COMBAT and CriSP-HS were screened and ultimately excluded from the final analysis as they did not meet eligibility criteria.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Stratified principal component (PC) analysis was performed for INR and thromboelastography values. Strata were defined based on AIS scores as: 1) isolated severe TBI (iTBI); 2) severe polytrauma (POLY), those with both major head injury and torso/extremity trauma; and 3) isolated severe torso/extremity trauma (iTRUNK). We identified 506 subjects with complete data: 51 iTBI, 115 POLY, and 340 iTRUNK. For each stratum, two PCs were identified that accounted for more than 65% of the variance. Associations between PC scores and outcomes, including need for blood product transfusion within 24 hours as a surrogate marker for early coagulopathy and bleeding, were examined with logistic regression. For both iTBI and POLY, PC1 included INR, AA, K time, and MA, and was associated with greater odds of early transfusion (odds ratio [OR], 3.57; 95% CI, 1.50-8.45; p = 0.004 for iTBI and OR, 2.29; 95% CI, 1.11-4.75; p = 0.026 for POLY). For iTRUNK, PC1 included INR, AA, and MA and was protective with reduced odds of early transfusion (OR, 0.51; 95% CI, 0.37-0.70; p < 0.001).

CONCLUSIONS: PC analysis demonstrated a unique pattern of coagulation biomarkers common to patients with severe TBI, irrespective of other injuries.