Specialist healthcare services for concussion/mild traumatic brain injury in England: a consensus statement using modified Delphi methodology.

OBJECTIVE: To establish a consensus on the structure and process of healthcare services for patients with concussion in England to facilitate better healthcare quality and patient outcome. DESIGN: This consensus study followed the modified Delphi methodology with five phases: participant identification, item development, two rounds of voting and a meeting to finalise the consensus statements. The predefined threshold for agreement was set at ≥70%. SETTING: Specialist outpatient services. PARTICIPANTS: Members of the UK Head Injury Network were invited to participate. The network consists of clinical specialists in head injury practising in emergency medicine, neurology, neuropsychology, neurosurgery, paediatric medicine, rehabilitation medicine and sports and exercise medicine in England. PRIMARY OUTCOME MEASURE: A consensus statement on the structure and process of specialist outpatient care for patients with concussion in England. RESULTS: 55 items were voted on in the first round. 29 items were removed following the first voting round and 3 items were removed following the second voting round. Items were modified where appropriate. A final 18 statements reached consensus covering 3 main topics in specialist healthcare services for concussion; care pathway to structured follow-up, prognosis and measures of recovery, and provision of outpatient clinics. CONCLUSIONS: This work presents statements on how the healthcare services for patients with concussion in England could be redesigned to meet their health needs. Future work will seek to implement these into the clinical pathway.

A Machine Learning Enhanced Mechanistic Simulation Framework for Functional Deficit Prediction in TBI.

Resting state functional magnetic resonance imaging (rsfMRI), and the underlying brain networks identified with it, have recently appeared as a promising avenue for the evaluation of functional deficits without the need for active patient participation. We hypothesize here that such alteration can be inferred from tissue damage within the network. From an engineering perspective, the numerical prediction of tissue mechanical damage following an impact remains computationally expensive. To this end, we propose a numerical framework aimed at predicting resting state network disruption for an arbitrary head impact, as described by the head velocity, location and angle of impact, and impactor shape. The proposed method uses a library of precalculated cases leveraged by a machine learning layer for efficient and quick prediction. The accuracy of the machine learning layer is illustrated with a dummy fall case, where the machine learning prediction is shown to closely match the full simulation results. The resulting framework is finally tested against the rsfMRI data of nine TBI patients scanned within 24 h of injury, for which paramedical information was used to reconstruct in silico the accident. While more clinical data are required for full validation, this approach opens the door to (i) on-the-fly prediction of rsfMRI alterations, readily measurable on clinical premises from paramedical data, and (ii) reverse-engineered accident reconstruction through rsfMRI measurements.

Central Retinal Artery Occlusion Following Prone Transcranial Surgery for Craniosynostosis and Discussion of Risk Factors.

Vision loss is a known rare complication of prone positioning during surgery. Vision loss following prone surgery is most commonly attributed to direct pressure on the eye but can also be caused by central retinal artery occlusion (CRAO) in the absence of pressure on the eye. Central retinal artery occlusion has not been previously described following prone transcranial surgery for craniosynostosis. We present two cases of monocular CRAO following prone calvarial expansion. A multidisciplinary root cause analysis suggested that raised intracranial pressure and intraoperative tranexamic acid may have been risk factors for the development of CRAO in these cases as no conventional risk factors for CRAO following prone surgery were present. Because of this, we retrospectively reviewed all prone transcranial procedures performed at the Oxford Craniofacial Unit for the presence of raised intracranial pressure and intraoperative tranexamic acid use. A total of 662 prone procedures have been performed between 1994 and March, 2019. Tranexamic acid has been used routinely in all transcranial procedures since 2012 and in the last 311 consecutive prone cases. Fifty-one (7.7%) prone procedures were performed for raised intracranial pressure, and tranexamic acid was used in the 33 most recent of these. Since the implementation of standard intraoperative administration of tranexamic acid there have been 2 cases of CRAO following prone surgery. The overall incidence of CRAO was 0.3% but was 6% in the context of raised intracranial pressure and tranexamic acid use. Prone positioning raised intracranial pressure and tranexamic acid use together may represent a potent combination of risk factors for CRAO.

Neuroimaging in the Diagnosis of Chronic Traumatic Encephalopathy: A Systematic Review.

OBJECTIVE: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repeated subconcussive and concussive head injury. Clinical features include cognitive, behavioral, mood, and motor impairments. Definitive diagnosis is only possible at postmortem. Here, the utility of neuroimaging in the diagnosis of CTE is evaluated by systematically reviewing recent evidence for changes in neuroimaging biomarkers in suspected cases of CTE compared with controls. DATA SOURCES: Providing an update on a previous systematic review of articles published until December 2014, we searched for articles published between December 2014 and July 2016. We searched PubMed for studies assessing neuroimaging changes in symptomatic suspected cases of CTE with a history of repeated subconcussive or concussive head injury or participation in contact sports involving direct impact to the head. Exclusion criteria were case studies, review articles, and articles focusing on repetitive head trauma from military service, head banging, epilepsy, physical abuse, or animal models. MAIN RESULTS: Seven articles met the review criteria, almost all of which studied professional athletes. The range of modalities were categorized into structural magnetic resonance imaging (MRI), diffusion MRI, and radionuclide studies. Biomarkers which differed significantly between suspected CTE and controls were Evans index (P = 0.05), cavum septum pellucidum (CSP) rate (P < 0.0006), length (P < 0.03) and ratio of CSP length to septum length (P < 0.03), regional differences in axial diffusivity (P < 0.05) and free/intracellular water fractions (P < 0.005), single-photon emission computed tomography perfusion abnormalities (P < 0.01), positron emission tomography (PET) signals from tau-binding, glucose-binding, and GABA receptor-binding radionuclides (P < 0.0001, P < 0.005, and P < 0.005, respectively). Important limitations include low specificity in identification of suspected cases of CTE across studies, the need for postmortem validation, and a lack of generalizability to nonprofessional athletes. CONCLUSIONS: The most promising biomarker is tau-binding radionuclide PET signal because it is most specific to the underlying neuropathology and differentiated CTE from both controls and patients with Alzheimer disease (P < 0.0001). Multimodal imaging will improve specificity further. Future research should minimize variability in identification of suspected cases of CTE using published clinical criteria.

Clinical decision support and improved blood use in patient blood management.

Despite many years of published medical society guidelines for red blood cell (RBC) transfusion therapy, along with clinical trials that provide Level 1 evidence that restrictive transfusion practices can be used safely and are equivalent to transfusions given more liberally, annualized blood transfusion activity did not begin to decline in the United States until 2010. Adoption of electronic medical records has subsequently allowed implementation of clinical decision support (CDS): best practice alerts that can be initiated to improve the use of blood components. We describe our own institutional experience using a targeted CDS to promote restrictive blood transfusion practice and to improve RBC use. A 42% reduction in RBC transfusions was demonstrated at our institution from a baseline in 2008 through 2015, and the rate remained stable through 2018. Although the data cannot be used to infer causality, this decreased RBC use was accompanied by improved clinical outcomes.

MRS and DTI evidence of progressive posterior cingulate cortex and corpus callosum injury in the hyper-acute phase after Traumatic Brain Injury.

The posterior cingulate cortex (PCC) and corpus callosum (CC) are susceptible to trauma, but injury often evades detection. PCC Metabolic disruption may predict CC white matter tract injury and the secondary cascade responsible for progression. While the time frame for the secondary cascade remains unclear in humans, the first 24 h (hyper-acute phase) are crucial for life-saving interventions. Objectives: To test whether Magnetic Resonance Imaging (MRI) markers are detectable in the hyper-acute phase and progress after traumatic brain injury (TBI) and whether alterations in these parameters reflect injury severity. Methods: Spectroscopic and diffusion-weighted MRI data were collected in 18 patients with TBI (within 24 h and repeated 7-15 days following injury) and 18 healthy controls (scanned once). Results: Within 24 h of TBI N-acetylaspartate was reduced (F = 11.43, p = 0.002) and choline increased (F = 10.67, p = 0.003), the latter driven by moderate-severe injury (F = 5.54, p = 0.03). Alterations in fractional anisotropy (FA) and axial diffusivity (AD) progressed between the two time-points in the splenium of the CC (p = 0.029 and p = 0.013). Gradual reductions in FA correlated with progressive increases in choline (p = 0.029). Conclusions: Metabolic disruption and structural injury can be detected within hours of trauma. Metabolic and diffusion parameters allow identification of severity and provide evidence of injury progression.

Oral vs intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review of randomized trials comparing oral vs intravenous (IV) iron therapy to treat postpartum anemia. DATA SOURCES: Data sources were as follows: PubMed (1972-2017); Cochrane Central Register of Controlled Trials, CENTRAL (1972-2017); CINAHL (1972-2017); Web of Science; Excerpta Medica Database, and EMBASE (1972-2017). STUDY ELIGIBILITY CRITERIA: We included randomized trials comparing oral vs IV iron monotherapy to treat postpartum anemia (classified as a hemoglobin <12 g/dL). STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed with the Cochrane risk of bias assessment tool. The primary outcome was hemoglobin concentration at 6 weeks postpartum. Secondary outcomes included hemoglobin concentration at 1-5 weeks postpartum, ferritin concentration at 1-6 weeks postpartum, and maternal adverse outcomes. For meta-analysis, mean differences and odds ratios using a random effects model were calculated. Risk of heterogeneity was reported as I2. RESULTS: A total of 15 randomized trials met our inclusion criteria (n = 1001 and 1 181 women receiving oral iron and IV iron, respectively); 4 studies reported data for our primary outcome. We observed higher postpartum week 6 hemoglobin concentrations in the IV iron group compared to the oral iron group (mean difference, 0.9 g/dL; 95% confidence interval (CI), 0.4-1.3; P = .0003). Compared to oral iron, women receiving IV iron had higher hemoglobin concentrations at postpartum weeks 1, 2, and 3; higher ferritin concentrations at postpartum weeks 1, 2, 4, and 6; an increased likelihood of skin flushing (odds ratio [OR], 6.95; 95% CI, 1.56-31.03; P = .01; I2 = 0%); and a decreased likelihood of constipation (OR, 0.08; 95% CI, 0.03-0.21; P < .00001, I2 = 27%) and dyspepsia (OR, 0.07; 95% confidence interval, 0.01-0.42; P = .004; I2 = 0%). The reported event rate for anaphylaxis among women receiving IV iron was 0.6%. CONCLUSION: In this systematic review, among women with postpartum anemia, hemoglobin concentrations at 6 weeks postpartum were almost 1 g/dL higher in women who received IV iron compared to oral iron. The safety profile of IV iron was also reassuring. Given the weaker hemoglobin response and higher risk of gastrointestinal side effects with oral iron use, our findings suggest that IV iron be considered as a viable treatment option for postpartum iron deficiency anemia.

Management of anemia in patients who decline blood transfusion.

Declining a treatment modality should not be considered the same as refusal of medical care as illustrated by the management of Jehovah's Witness patients who do not accept transfusions. Over the years, a comprehensive set of strategies have been developed to meet the specific needs of these patients and these strategies are collectively called "Bloodless Medicine and Surgery" (BMS). The focus in BMS is to optimize the patients' hematopoietic capacity to increase hemoglobin (Hgb) level, minimize blood loss, improve hemostasis, and provide supportive strategies to minimize oxygen consumption and maximize oxygen utilization. We present 3 case reports that illustrate some of the challenges faced and measures available to effectively treat these patients. Under BMS programs, patients with extremely low hemoglobin levels, not conducive to survival under ordinary conditions, have survived and recovered without receiving allogeneic transfusions. Additionally, the valuable experience gained from caring for these patients has paved the way to develop the concept of Patient Blood Management as a standard care to benefit all patients, and not only those for whom blood is not an option.

Early detection of cerebral microbleeds following traumatic brain injury using MRI in the hyper-acute phase.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in people under 45. Advanced imaging techniques to identify injury and classify severity in the first few hours and days following trauma could improve patient stratification and aid clinical decision making. Traumatic cerebral microbleeds (TCMBs), detectable on magnetic resonance susceptibility weighted imaging (SWI), can be used as markers of long-term clinical outcome. However, the relationship between TCMBs and injury severity in the first few hours after injury, and their natural evolution, is unknown. METHODS: We obtained SWI scans in 10 healthy controls, and 13 patients scanned 3-24h following TBI and again at 7-15days. TCMBs were identified and total volume quantified for every lesion in each scan. RESULTS: TCMBs were present in 6 patients, all with more severe injury classified by GCS. No lesions were identified in patients with an initial GCS of 15. Improvement in GCS in the first 15days following injury was significantly associated with a reduction in microbleed volume over the same time-period. CONCLUSION: MRI is feasible in severely injured patients in the first 24h after trauma. Detection of TCMBs using SWI provides an objective early marker of injury severity following trauma. TCMBs revealed in this time frame, offer the potential to help determine the degree of injury, improving stratification, in order to identify patients who require admission to hospital, transfer to a specialist center, or an extended period of intubation on intensive care.

A Standardized Approach for Transfusion Medicine Support in Patients With Morbidly Adherent Placenta.

BACKGROUND: The incidence of placenta accreta (PA) has increased from 0.8 to 3.0 in 1000 pregnancies, driven by increased rates of cesarean deliveries (32.2% in 2014) of births in the United States. The average blood loss for a delivery complicated by PA ranges from 2000 to 5000 mL, frequently requiring substantial transfusion medicine support. We report our own institutional multidisciplinary approach for managing such patients, along with transfusion medicine outcomes, in this setting over a 5-year period. METHODS: We reviewed records for patients referred to our program in placental disorders from July 1, 2009, to July 1, 2014. A placental disorders preoperative checklist was implemented to ensure optimal management of patients with peripartum hemorrhage. RESULTS: Of 136 patients whose placentas were reviewed postpartum, 21 had PA, 39 had microscopic PA, 17 had increta, 17 had percreta, and 42 had no accreta (of which 11 had placenta previa). For each subtype, the percentage of patients receiving blood products were 71% (PA), 28% (microscopic PA), 82% (increta), 82% (percreta), and 19% (no accreta). Among patients with PA or variants, 89% of patients with PA or variants underwent postpartum hysterectomy, compared to only 5% of patients with no or microscopic PA. CONCLUSIONS: Based on our experience and on the findings of our retrospective analysis, patients presenting with either antepartum radiological evidence or clinical suspicion of morbidly adherent placenta will benefit from a standardized protocol for clinical management, including transfusion medicine support. We found that massive hemorrhage is predictable when abnormal placentation is identified predelivery and that blood product support is substantial regardless of the degree of placental invasiveness. The protocol at our institution provides immediate access to sufficient volumes and types of blood products at delivery for patients at highest risk for life-threatening obstetric hemorrhage. Therefore, for patients with a diagnosis of morbidly adherent placenta scheduled for planned cesarean delivery with possible hysterectomy, a programmatic checklist that mobilizes a multidisciplinary team, including proactive transfusion medicine support, represents best practices.

Blood Transfusion Therapy.

Transfusion of red blood cells (RBCs) is a balance between providing benefit for patients while avoiding risks of transfusion. Randomized, controlled trials of restrictive RBC transfusion practices have shown equivalent patient outcomes compared with liberal transfusion practices, and meta-analyses have shown improved in-hospital mortality, reduced cardiac events, and reduced bacterial infections. This body of level 1 evidence has led to substantial, improved blood utilization and reduction of inappropriate blood transfusions with implementation of clinical decision support via electronic medical records, along with accompanying educational initiatives.

Patient Blood Management Bundles to Facilitate Implementation.

More than 30% of the world's population are anemic with serious economic consequences including reduced work capacity and other obstacles to national welfare and development. Red blood cell transfusion is the mainstay to correct anemia, but it is also 1 of the top 5 overused procedures. Patient blood management (PBM) is a proactive, patient-centered, and multidisciplinary approach to manage anemia, optimize hemostasis, minimize iatrogenic blood loss, and harness tolerance to anemia. Although the World Health Organization has endorsed PBM in 2010, many hospitals still seek guidance with the implementation of PBM in clinical routine. Given the use of proven change management principles, we propose simple, cost-effective measures enabling any hospital to reduce both anemia and red blood cell transfusions in surgical and medical patients. This article provides comprehensive bundles of PBM components encompassing 107 different PBM measures, divided into 6 bundle blocks acting as a working template to develop institutions' individual PBM practices for hospitals beginning a program or trying to improve an already existing program. A stepwise selection of the most feasible measures will facilitate the implementation of PBM. In this manner, PBM represents a new quality and safety standard.

How I train specialists in transfusion medicine.

BACKGROUND: The changing focus of transfusion medicine (TM) toward the hospital rather than the blood center and the involvement of TM specialists in a wide range of patient blood management and other specialist activities in the hospital, rather than just blood bank activities, means that the training of the transfusion specialists of the future should be under constant review. STUDY DESIGN AND METHODS: We provide overviews of the current training programs of the Accreditation Council for Graduate Medical Education in the United States and the Joint Royal Colleges of Physicians Training Board in the United Kingdom, along with specific descriptions of our own training programs at Stanford and Oxford. RESULTS: The numbers of TM fellows in training annually in the United States and of those who attempt to attain board certification have increased substantially over the last 20 years, despite the profound reduction in blood utilization since 2009. These trends reflect increasing job and career opportunities in new activities, such as patient blood management at hospital-based transfusion services. This trend has been seen to a lesser extent in the United Kingdom, although the focus of TM is similarly switching to hospital-based transfusion services. CONCLUSION: Based on current trends, transfusion medicine is a growing and robust specialty in the United States but perhaps less so in the United Kingdom, increasingly with hospital-centered job opportunities for improving blood utilization and clinical outcomes. Establishing pediatric TM training programs and improving research training are further opportunities for training TM specialists.

Knowledge of blood loss at delivery among postpartum patients.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of obstetric morbidity. There is limited understanding of patients' knowledge about blood loss at delivery, PPH, and PPH-related morbidities, including transfusion and anemia. METHODS: We surveyed 100 healthy postpartum patients who underwent vaginal or cesarean delivery about blood loss, and whether they received information about transfusion and peripartum hemoglobin (Hb) testing. Responses were compared between women undergoing vaginal delivery vs. cesarean delivery; P < 0.05 considered as statistically significant. RESULTS: In our cohort, 49 women underwent vaginal delivery and 51 women underwent cesarean delivery. Only 29 (29%) of women provided blood loss estimates for their delivery. Women who underwent cesarean delivery were more likely to receive clear information about transfusion therapy than those undergoing vaginal delivery (43.1% vs. 20.4% respectively; P = 0.04). Women who underwent vaginal delivery were more likely to receive results of postpartum Hb tests compared to those undergoing cesarean delivery (49% vs. 29.4%; P = 0.02). CONCLUSION: Our findings suggest that women are poorly informed about the magnitude of blood loss at delivery. Hematologic information given to patients varies according to mode of delivery. Further research is needed to better understand the clinical implications of patients' knowledge gaps about PPH, transfusion and postpartum anemia.

Transportation Cooler Interventions Reduce Plasma and RBC Product Wastage.

OBJECTIVES: The rate of plasma product wastage for the United States in 2011 was approximately 1.8%. The plasma wastage rate at our institution was higher, mainly due to products returned out of temperature range from procedural areas. A process review and intervention to reduce plasma wastage was undertaken, which included modifications to our transport cooler. METHODS: A new cooler system was designed, and this device was implemented alongside an updated protocol for delivering plasma while also enhancing the previous RBC cooler validation time. We audited plasma and RBC product wastage prior to these interventions, from January 2013 to February 2014, vs after the intervention from April 2014 to March 2015. RESULTS: After the intervention, the monthly plasma wastage rate declined 60% (12.6 units/100 units transfused preintervention vs 5.0 units/100 units transfused postintervention; P < .0001). The monthly RBC wastage rate also decreased 28% (3.2 units/100 units transfused preintervention vs 2.3 units/100 units transfused postintervention; P < .01). CONCLUSIONS: Our intervention resulted in significantly decreased plasma and RBC wastage and is broadly applicable, since out-of-temperature product wastage in procedural areas is likely a significant problem at many institutions.