The Risk of Hemorrhagic Complications After Anticoagulation Therapy in Trauma Patients: A Multicenter Evaluation.

BACKGROUND: The use of anticoagulation therapy (ACT) in trauma patients during the post-injury period presents a challenge given the increased risk of hemorrhage. Guidelines regarding whether and when to initiate ACT are lacking, and as a result, practice patterns vary widely. The purpose of this study is to describe the incidence of hemorrhagic complications in patients who received ACT during their hospitalization, identify risk factors, and characterize the required interventions. METHODS: In this retrospective cohort study, all trauma admissions at two Level 1 trauma centers between January 2015 and December 2020 were reviewed. Patients with pre-existing ACT use or those who developed a new indication for ACT were included for analysis. Demographic and outcome data were collected for those who received ACT during their admission. Comparisons were then made between the complications and no complications groups. A subgroup analysis was performed for all patients started on ACT within 14 days of injury. RESULTS: A total of 812 patients were identified as having an indication for ACT, and 442 patients received ACT during the post-injury period. The overall incidence of hemorrhagic complications was 12.7%. Of those who sustained hemorrhagic complications, 18 required procedural intervention. On regression analysis, male sex, severe injuries, and the need for hemorrhage control surgery on arrival were all found to be associated with hemorrhagic complications after the initiation of ACT. Waiting 7-14 days from the time of injury to initiate ACT reduced the odds of complications by 46% and 71%, respectively. CONCLUSIONS: The use of ACT in trauma during the post-injury period is not without risk. Waiting 7-14 days post-injury might greatly reduce the risk of hemorrhagic complications. STUDY TYPE/LEVEL OF EVIDENCE: Therapeutic/care management study: Level IV.

Direct Dispensation of Prenatal Supplements With Iron and Anemia Among Pregnant People.

Importance: Postpartum transfusion is the most common indicator of severe maternal morbidity in the US. Higher rates of anemia are associated with a higher blood transfusion rate. Objective: To determine if providing, rather than recommending, supplements with iron at prenatal visits in a medically underserved community is associated with improved hematologic indices and reduced blood transfusion. Design, Setting, and Participants: In this quality improvement study, patients who delivered between May 13 and December 13, 2020, and thus were provided a prenatal supplement with iron throughout pregnancy were compared with those who delivered between January 1 and August 1, 2019, before supplements were dispensed. The study was conducted at Parkland Health, a safety net hospital in Dallas, Texas, with a 95% Medicaid-funded or self-pay population and included all patients who delivered at our institution during the study period with available hematologic data. Exposures: In the earlier cohort, all patients were recommended to obtain and take iron supplements. In the later cohort, prenatal supplements with iron were dispensed via clinic pharmacy to all patients during prenatal visits. Main Outcomes and Measures: Maternal hematocrit levels (28-32 weeks, delivery admission, and discharge), rates of anemia (hematocrit <30%), and postpartum transfusion for acute blood loss anemia were compared using χ2 and analysis of variance methods with P < .05 considered significant. The analysis took place in July of 2022. Results: Overall, 13 910 patients (98%) met inclusion criteria (mean age [SD], 27.9 [6.5] and 27.6 [6.5] years, mean [SD] body mass index at first visit, 29.2 [6.6] and 29.3 [6.6]). Mosty of the patients in both cohorts were of Hispanic ethnicity (76%). Providing iron-containing prenatal supplements was associated with higher average hematocrit levels at all time points including a mean difference of 1.27% (95% CI, 1.13%-1.42%) on admission for delivery, when compared with those who were not directly dispensed iron. Among patients prior to providing supplements, 18% had anemia on admission compared with 11% with iron-containing supplements dispensed (risk ratio [RR], 0.61; 95% CI, 0.56-0.66). Postpartum transfusion for acute blood loss anemia was reduced by one-third in patients after program implementation from 10 per 1000 to 6.6 per 1000 (RR, 0.62; 95% CI, 0.43-0.91). Conclusions and Relevance: In this quality improvement study, providing supplements with iron to patients at prenatal visits was associated with improved hematocrit levels, rates of anemia, and reduced transfusions unrelated to obstetric catastrophes among a predominantly Medicaid population.

Inclusion of Pregnant and Lactating People in Clinical Research: Lessons Learned and Opportunities.

Pregnant and lactating individuals historically have been excluded from research studies because of the ethical concerns surrounding potential harm to the fetus. Several National Institutes of Health and Food and Drug Administration initiatives have attempted to improve inclusion; however, clinical trials continue to exclude pregnant and lactating people. Drug labeling for safety and efficacy in pregnancy has thus been forced to rely on data from animal studies or limited case reports. Recent changes have sought to improve prescriber understanding of risks, benefits, and limitations of safety information on medications; however, confusion persists.

CNS Antigen-Specific Neuroinflammation Attenuates Ischemic Stroke With Involvement of Polarized Myeloid Cells.

BACKGROUND AND OBJECTIVES: Experimental studies indicate shared molecular pathomechanisms in cerebral hypoxia-ischemia and autoimmune neuroinflammation. This has led to clinical studies investigating the effects of immunomodulatory therapies approved in multiple sclerosis on inflammatory damage in stroke. So far, mutual and combined interactions of autoimmune, CNS antigen-specific inflammatory reactions and cerebral ischemia have not been investigated so far. METHODS: Active MOG35-55 experimental autoimmune encephalomyelitis (EAE) was induced in male C57Bl/6J mice. During different phases of EAE, transient middle cerebral artery occlusion (tMCAO, 60 minutes) was induced. Brain tissue was analyzed for infarct size and immune cell infiltration. Multiplex gene expression analysis was performed for 186 genes associated with neuroinflammation and hypoxic-ischemic damage. RESULTS: Mice with severe EAE disease showed a substantial reduction in infarct size after tMCAO. Histopathologic analysis showed less infiltration of CD45+ hematopoietic cells in the infarct core of severely diseased acute EAE mice; this was accompanied by an accumulation of Arginase1-positive/Iba1-positive cells. Gene expression analysis indicated an involvement of myeloid cell-driven anti-inflammatory mechanisms in the attenuation of ischemic injury in severely diseased mice exposed to tMCAO in the acute EAE phase. DISCUSSION: CNS autoantigen-specific autoimmunity has a protective influence on primary tissue damage after experimental stroke, indicating a very early involvement of CNS antigen-specific, myeloid cell-associated anti-inflammatory immune mechanisms that mitigate ischemic injury in the acute EAE phase.

Acute clinical deterioration and consumer escalation: The understanding and perceptions of hospital staff.

INTRODUCTION: Consumer escalation systems allow patients and families to escalate concerns about acute clinical deterioration. Hospital staff can impact upon the success of this process. As part of evaluation processes within a Local Health Network, where a consumer escalation system was introduced in accordance with National requirements, we sought to explore clinicians' understanding and perceptions of consumer escalation. METHODS: Voluntary and anonymous staff surveys pre, and post, system introduction. Quantitative data was analysed using descriptive statistics, chi-square independence, and non-parametric independent samples median tests. Qualitative data was evaluated using content analysis and cross-referenced with quantitative responses. RESULTS: Respondent's (pre: 215; post: 89) area of work varied significantly between survey periods. Most agreed that patients/families have a sound knowledge of a patient's typical health status (pre: 192/215 (89.3%); post 82/88 (93.2%)) and that patients/families should be encouraged to escalate concerns of deterioration to ward staff (pre: 209/212 (98.6%); post: 85/89 (95.5%)). Respondent perceptions of patient/family ability to recognise clinical deterioration varied. Staff agreement towards local response expectations decreased as the degree of clinical requirement increased. Staff concerns of increased workloads (pre: 90/214 (42.1%); post 12/72 (16.7%), p<0.001) and conflict generation (pre: 71/213 (33.3%); post: 7/71 (9.9%), p = 0.001) decreased significantly following system introduction. However, clinician perceptions of positive system effects also decreased (patient-staff rapport pre: 163/213 (76.5%); post: 38/72 (52.8%), p = 0.001; patient centred care pre: 188/214 (87.9%); post: 53/72 (73.6%), p = 0.012; patient safety pre: 173/214 (80.8%); post: 49/72 (68.1%), p = 0.077). Only 53% of respondents (pre: 112/213 (52.6%); post: 48/88 (54.5%)) perceived that patient/family have sufficient confidence to escalate concerns. CONCLUSION: Consumer escalation systems require staff support. Staff perceptions may indicate, and act as, barriers to the operation of consumer escalation processes. Further exploration in identifying and managing staff barriers is crucial to the success of consumer escalation.

Natural history of postpartum hematocrit recovery in an urban, safety-net population.

BACKGROUND: Postpartum anemia is common after delivery, and postpartum blood transfusion is the leading indicator of severe maternal morbidity in the United States. Although hematologic changes during the antepartum period are well understood, little is known about postpartum hematologic changes. Therefore, we investigated the hematologic changes in the postpartum period in a large, contemporary cohort. OBJECTIVE: This study aimed to characterize hematologic recovery in the postpartum period and evaluate the effect of demographics, medical conditions, and pregnancy characteristics on the recovery. STUDY DESIGN: In a contemporary cohort of deliveries in 2019 at a single institution, the hematocrit of postpartum women before hospital discharge was compared with the hematocrit of women at the postpartum follow-up. Our population was composed of a predominantly Hispanic population at an urban, safety-net hospital. All women received a complete blood count on postpartum day 1 and a spun hematocrit at their postpartum follow-up visit in our hospital system. All women were scheduled for a routine postpartum visit 2 to 3 weeks after delivery. All deliveries of a live-born infant with available postpartum hematocrit before hospital discharge and at postpartum follow-up were included. Demographics and pregnancy characteristics, along with medical conditions, were evaluated. To evaluate an uncomplicated cohort, those with multiple gestation, preeclampsia with severe features, chronic hypertension, and diabetes mellitus were excluded in the secondary analysis. Statistical analysis included chi-square, paired Student t test, Student t test for independent groups, and analysis of variance. RESULTS: Of 12,456 deliveries, 9003 met the inclusion criteria. The average number of days from discharge to follow-up was 21.73±10.39 days. The average hematocrit levels were 30.77±3.61 before discharge and 38.70±3.61 at postpartum follow-up. From discharge to postpartum follow-up, the hematocrit levels increased by an average of 7.93±3.24. In the cohort without complications, the average increase in hematocrit levels was 8.19±3.09. The rise in hematocrit levels was significantly lower for those with chronic hypertension (6.9±3.6), diabetes mellitus (7.3±3.3), and preeclampsia with severe features (6.9±3.7). The severity of anemia influenced the rise in hematocrit levels in the postpartum period. In women with postpartum anemia (hematocrit<30%), the rise in hematocrit levels was 9.49±2.97 in the uncomplicated cohort. Postpartum hemorrhage did not influence the rise in postpartum hematocrit levels; women receiving blood transfusion had a greater rise in hematocrit levels (9.01±3.29). CONCLUSION: Our study establishes the natural course of hematologic recovery in the postpartum period, and we found that women with asymptomatic postpartum anemia may have a hematocrit level of 37% to 39% at their postpartum follow-up approximately 3 weeks after hospital discharge. Women with preexisting and obstetrical complications experienced less hematologic recovery and adapted more slowly to postpartum physiological changes.

Acute clinical deterioration and consumer escalation in the hospital setting: A literature review.

BACKGROUND: Consumer escalation systems that allow patients and/or their family/carers to escalate concerns about clinical deterioration have been proposed as a way of enhancing patient safety. However, evidence to guide implementation or to support system effectiveness remains unclear. AIM: To critically evaluate the current evidence surrounding consumer escalation within the context of clinical deterioration to identify the strengths, weaknesses and gaps in existing knowledge, essential themes, and directions for further investigation. METHOD: Database searches were conducted within Cumulative Index of Nursing and Allied Health Literature, PubMed, and the Cochrane Library for articles directly relating to consumer escalation systems published, in English, within the previous 10 year-period. Titles and abstracts were screened and relevant full-text articles included. Content was examined to identify breadth of knowledge, essential themes, and the effectiveness of current systems. RESULTS: 27 articles, containing a mixture of both quantitative and qualitative findings, were identified. Within the context of limitations in the overall depth and quality of current evidence, four key areas (relating to consumer understanding and awareness of clinical deterioration, confidence and ability to escalate concerns, education, and staff attitudes) were identified as potentially critical to the foundation, functioning, and success of consumer escalation systems. Consumer escalation processes may contribute positive effects beyond mortality rates; however, an agreed method of assessing effectiveness remains undetermined. CONCLUSIONS: The ability of consumer escalation processes to achieve their underlying goals is still to be adequately assessed. Further research is required to inform how to best implement, support and optimise consumer escalation systems.

A systematic approach to identify recycling endocytic cargo depending on the GARP complex.

Proteins and lipids of the plasma membrane underlie constant remodeling via a combination of the secretory- and the endocytic pathway. In the yeast endocytic pathway, cargo is sorted for recycling to the plasma membrane or degradation in vacuoles. Previously we have shown a role for the GARP complex in sphingolipid sorting and homeostasis (Fröhlich et al. 2015). However, the majority of cargo sorted in a GARP dependent process remain largely unknown. Here we use auxin induced degradation of GARP combined with mass spectrometry based vacuolar proteomics and lipidomics to show that recycling of two specific groups of proteins, the amino-phospholipid flippases and cell wall synthesis proteins depends on a functional GARP complex. Our results suggest that mis-sorting of flippases and remodeling of the lipid composition are the first occurring defects in GARP mutants. Our assay can be adapted to systematically map cargo of the entire endocytic pathway.