Fibrinogen Early In Severe paediatric Trauma studY (FEISTY junior): protocol for a randomised controlled trial.

INTRODUCTION: Trauma causes 40% of child deaths in high-income countries, with haemorrhage being a leading contributor to death in this population. There is a growing recognition that fibrinogen and platelets play a major role in trauma-induced coagulopathy (TIC) but the exact physiological mechanisms are poorly understood. METHODS AND ANALYSIS: This is a prospective multicentre, open-label, randomised, two-arm parallel feasibility study conducted in the emergency departments, intensive care units and operating theatres of participating hospitals. Severely injured children, aged between 3 months and 18 years, presenting with traumatic haemorrhage requiring transfusion of blood products will be screened for inclusion.Sixty-eight patients will be recruited and will be allocated to fibrinogen replacement using fibrinogen concentrate (FC) or cryoprecipitate in a 1:1 ratio. Fibrinogen replacement will be administered to patients with a FIBTEM A5 of ≤10. All other aspects of the currently used rotational thromboelastometry-guided treatment algorithm and damage-control approach to trauma remain the same in both groups.The primary outcome is time to administration of fibrinogen replacement from time of identification of hypofibrinogenaemia. Clinical secondary outcomes and feasibility outcomes will also be analysed. ETHICS AND DISSEMINATION: This study has received ethical clearance from the Children's Health Queensland Human Research Ethics Committee (HREC/17/QRCH/78). Equipment and consumables for sample testing have been provided to the study by Haemoview Diagnostics, Werfen Australia and Haemonetics Australia. FC has been provided by CSL Behring, Australia. The funding bodies and industry partners have had no input into the design of the study, and will not be involved in the preparation or submission of the manuscript for publication.The use of viscoelastic haemostatic assays and early fibrinogen replacement has the potential to improve outcomes in paediatric trauma through earlier recognition of TIC. This in turn may reduce transfusion volumes and downstream complications and reduce the reliance on donor blood products such as cryoprecipitate.The use of FC has implications for regional and remote centres who would not routinely have access to cryoprecipitate but could store FC easily. Access to early fibrinogen replacement in these centres could make a significant impact and assist in closing the gap in trauma care available to residents of these communities.Outcomes of this study will be submitted for publication in peer-reviewed journals and submitted for presentation at national and international scientific fora. TRIAL REGISTRATION NUMBER: NCT03508141.

Functional interaction between compound heterozygous TERT mutations causes severe telomere biology disorder.

Telomere biology disorders (TBDs) are a spectrum of multisystem inherited disorders characterized by bone marrow failure, resulting from mutations in the genes encoding telomerase or other proteins involved in maintaining telomere length and integrity. Pathogenicity of variants in these genes can be hard to evaluate, because TBD mutations show highly variable penetrance and genetic anticipation related to inheritance of shorter telomeres with each generation. Thus, detailed functional analysis of newly identified variants is often essential. Herein, we describe a patient with compound heterozygous variants in the TERT gene, which encodes the catalytic subunit of telomerase, hTERT. This patient had the extremely severe Hoyeraal-Hreidarsson form of TBD, although his heterozygous parents were clinically unaffected. Molecular dynamic modeling and detailed biochemical analyses demonstrate that one allele (L557P) affects association of hTERT with its cognate RNA component hTR, whereas the other (K1050E) affects the binding of telomerase to its DNA substrate and enzyme processivity. Unexpectedly, the data demonstrate a functional interaction between the proteins encoded by the two alleles, with wild-type hTERT rescuing the effect of K1050E on processivity, whereas L557P hTERT does not. These data contribute to the mechanistic understanding of telomerase, indicating that RNA binding in one hTERT molecule affects the processivity of telomere addition by the other molecule. This work emphasizes the importance of functional characterization of TERT variants to reach a definitive molecular diagnosis for patients with TBD, and, in particular, it illustrates the importance of analyzing the effects of compound heterozygous variants in combination, to reveal interallelic effects.

Routine Catheter Lock Solutions in Pediatric Cancer Care: A Pilot Randomized Controlled Trial of Heparin vs Saline.

BACKGROUND: Central venous access devices (CVADs) are integral to cancer care provision. Despite the high prevalence of CVAD complications in children with cancer, preventative strategies are understudied. OBJECTIVE: The aim of this study was to assess study feasibility, occlusive events, thrombolytic use, adverse events, and direct costs of catheter lock solutions. METHODS: A single-center, parallel-group, pilot randomized controlled trial was undertaken at a tertiary-referral pediatric hospital in Australia. Children 18 years or younger with an oncological or malignant hematological condition and a CVAD were eligible. Participants were 1:1 randomized to (1) normal or (2) heparinized (10-100 U/mL; CVAD-type dependent) saline lock solutions. RESULTS: Of 217 children assessed for eligibility, 61 were recruited and randomized to normal (n = 30; 3850 CVAD days) or heparinized (n = 31; 4036 CVAD days) saline. Eligibility (52%) and recruitment (54%) feasibility targets were not met. Protocol adherence was high (95% assessments), with no attrition. Parent/clinician satisfaction of interventions was high (median, 10/10 clinicians/parents). Complete CVAD occlusion occurred in heparin only (n = 2, 6.7% CVADs; incidence rate [IR], 0.49/1000 CVAD days [0.06-1.78]). Central venous access device partial occlusion was detected in 23.3% of CVADs in heparin (n = 7; IR, 2.73/1000 CVAD days [1.36-4.87]) and 13.8% of CVADs in normal saline (n = 4; IR, 2.59/1000 CVAD days [1.24-4.77]). Thrombolytic agents were used in 16.7% heparin (5 CVADs) and 3.5% normal saline (1 CVAD). Adverse events did not differ between groups. CONCLUSION: Multisite randomized controlled trials examining CVAD locks are safe, but strategies and resources to increase recruitment and eligibility are required. IMPLICATIONS FOR PRACTICE: Both routine CVAD lock solutions seem safe but may not prevent all forms of CVAD-associated harm.

Management of Submassive Bilateral Pulmonary Embolism in an Adolescent Female.

Pulmonary embolism (PE) is a rare presentation in the pediatric population. We report a case of submassive PE in an adolescent female following commencement of a combined oral contraceptive pill (COCP). In the setting of cardiac dysfunction, she received systemic thrombolysis with significant reduction of clot burden and clinical improvement objectively demonstrated shortly thereafter. This case highlights challenges in clinical decision-making regarding surgical or catheter-based interventions versus medical management approaches when addressing life-threatening PE in children. Our case demonstrates that submassive PE in pediatrics can be managed successfully with systemic thrombolysis and therapeutic anticoagulation.

Pediatric Thromboelastograph 6s and Laboratory Coagulation Reference Values.

CONTEXT.­: Specific reference intervals (RIs) facilitate accurate interpretation of results. Coagulation assay results may vary by demographics and also between reagents and analyzers used. Current Thromboelastograph 6s (TEG 6s) Hemostasis Analyzer RIs were generated from adult samples. OBJECTIVE.­: To generate reagent analyzer-specific pediatric RIs for TEG 6s and coagulation parameters. DESIGN.­: A prospective, observational, single-center study of healthy children undergoing general anesthesia (January 3, 2017 to January 3, 2019). Venous blood samples were obtained for TEG 6s (Kaolin, Kaolin-Heparinase, Rapid and Functional Fibrinogen assays) and coagulation parameters (activated partial thromboplastin time, prothrombin time, thrombin clotting time, Echis time, antithrombin activity, and fibrinogen concentration using Instrumentation Laboratory ACL-TOP analyzers). Differences between activated partial thromboplastin time and prothrombin time reagents were investigated using mixed-effects regression, comparing maximum coefficients-of-variation with assay-specific allowable variation. RIs (lower/upper limits 2.5th of 97.5th percentiles) were generated using the following 2 methods: within discrete age-groups (neonates [<1 month], infants [1 month-1 year], young children [1-5 years], older children [6-10 years], and adolescents [11-16 years]), and modeled as functions of age and/or sex using quantile regression, including significant fractional polynomial and interaction terms. RESULTS.­: Variation between prothrombin time and activated partial thromboplastin time assays using different reagents was clinically significant. Reagent-analyzer specific pediatric RIs were generated using data from 254 children. Discrete and model-based RIs varied by age for all coagulation parameters and TEG 6s variables in all assays. CONCLUSIONS.­: We report reagent-analyzer specific pediatric RIs for TEG 6s and coagulation parameters. Observed variation reinforces recommendations for laboratory-specific RIs. These findings improve accuracy of interpretation of clinical results, provide a foundation for comparison and validation of tests in pathology, and illustrate feasibility and advantages of model-based RI approaches.

Utility of clinical comprehensive genomic characterization for diagnostic categorization in patients presenting with hypocellular bone marrow failure syndromes.

Bone marrow failure (BMF) related to hypoplasia of hematopoietic elements in the bone marrow is a heterogeneous clinical entity with a broad differential diagnosis including both inherited and acquired causes. Accurate diagnostic categorization is critical to optimal patient care and detection of genomic variants in these patients may provide this important diagnostic and prognostic information. We performed real-time, accredited (ISO15189) comprehensive genomic characterization including targeted sequencing and whole exome sequencing in 115 patients with BMF syndrome (median age 24 years, range 3 months - 81 years). In patients with clinical diagnoses of inherited BMF syndromes, acquired BMF syndromes or clinically unclassifiable BMF we detected variants in 52% (12/23), 53% (25/47) and 56% (25/45) respectively. Genomic characterization resulted in a change of diagnosis in 30/115 (26%) including the identification of germline causes for 3/47 and 16/45 cases with pre-test diagnoses of acquired and clinically unclassifiable BMF respectively. The observed clinical impact of accurate diagnostic categorization included choice to perform allogeneic stem cell transplantation, disease-specific targeted treatments, identification of at-risk family members and influence of sibling allogeneic stem cell donor choice. Multiple novel pathogenic variants and copy number changes were identified in our cohort including in TERT, FANCA, RPS7 and SAMD9. Whole exome sequence analysis facilitated the identification of variants in two genes not typically associated with a primary clinical manifestation of BMF but also demonstrated reduced sensitivity for detecting low level acquired variants. In conclusion, genomic characterization can improve diagnostic categorization of patients presenting with hypoplastic BMF syndromes and should be routinely performed in this group of patients.

Testicular Workup for Ischemia and Suspected Torsion in Pediatric Patients and Resource Utilization.

BACKGROUND: Testicular torsion (TT) is a pediatric emergency requiring prompt diagnosis and management. The Testicular Workup for Ischemia and Suspected Torsion (TWIST) scores patients on clinical symptoms and can predict TT. This study aimed to determine if the application of TWIST to children with acute scrotal pain could decrease the use of Doppler ultrasonography (DUS) and emergency department (ED) length of stay and ischemic time. MATERIALS AND METHODS: A retrospective cohort study applying TWIST to patients who presented to a pediatric ED with acute testicular pain from December 2017 to June 2019 was performed. Demographics, TWIST score, diagnosis, DUS, consults, and time to the operation were recorded. Patients were stratified into low (LR), intermediate (IR), and high (HR) risk groups for TT based on TWIST score. Descriptive and comparative analyses were performed. RESULTS: Seventy-seven patients were included in the study and had a mean age of 9.24 y ±5.24. All 9 HR patients (TWIST = 5-7) had TT, and none of the 57 LR patients (TWIST = 0-2) had TT. Use of TWIST could have reduced the number of DUS needed to diagnose TT from 69 to 11 (75.3% reduction in DUS). CONCLUSIONS: TWIST accurately predicts torsion in HR groups and excludes torsion in LR groups. Application of TWIST to HR patients may eliminate the need for DUS and decrease ischemic time and cost of care. Application of TWIST in LR patients may likewise eliminate the need for DUS and decrease ED length of stay and cost of care.

Romiplostim treatment for children with immune thrombocytopenia: Results of an integrated database of five clinical trials.

BACKGROUND: Treatment for chronic immune thrombocytopenia (cITP) in children is largely limited to immunosuppressive agents. Thrombopoietin receptor agonists (TRAs) have been used to treat cITP in adults for over a decade. The objective of this integrated analysis was to examine the safety and efficacy of the TRA romiplostim in children with ITP. METHODS: We examined efficacy and safety in children with ITP across five romiplostim trials: final data from two double-blind placebo-controlled trials and two open-label extensions, and interim data from an ongoing single-arm trial. RESULTS: Patients (n = 24 initially placebo; n = 262 initially romiplostim) had a median age of 10.0 years (Q1: 6.0, Q3: 13.0), ITP duration of 1.9 years (Q1: 1.0, Q3: 4.0), and baseline platelet count of 14.3 × 109 /L (Q1: 7.5, Q3: 23.0). Among 282 patients receiving romiplostim, median treatment duration was 65 weeks (range 8-471 weeks) and median weekly dose was 6.6 µg/kg (range 0.1-9.7 µg/kg). Overall, 89% of romiplostim-treated patients had platelet responses. Nineteen patients (7%) maintained treatment-free responses for ≥6 months while withholding all ITP therapy. Grade 3 and 4 adverse events of bleeding occurred in 10% and <1% of romiplostim-treated patients, respectively. Twenty-five percent of patients had a serious adverse event, most commonly epistaxis (6%). Seven patients (2%) had neutralizing antibodies against romiplostim postbaseline and none had neutralizing antibodies against endogenous thrombopoietin. Efficacy and safety results appeared similar between children with ITP for ≤12 months and >12 months at baseline. CONCLUSIONS: Across five pediatric clinical trials, romiplostim was well tolerated. Most patients had a platelet response; some maintained responses for at least 6 months while withholding all ITP therapy.

Viscoelastic haemostatic assays and fibrinogen in paediatric acute traumatic coagulopathy: A comprehensive review.

OBJECTIVE: Haemorrhage in paediatric trauma remains a significant cause of morbidity and mortality. Over recent years there has been increasing attention to the role of fibrinogen in traumatic haemorrhage and the association of low fibrinogen levels with poor patient outcomes. In addition, there has been a move towards using viscoelastic haemostatic assays (VHAs) to rapidly assess coagulation status and guide clinicians in the replacement of coagulation factors, including fibrinogen. In the paediatric population, there has been limited uptake of these principles and a paucity of data to support a change in practice. This paper summarises the available evidence in the published literature through a systematic review, presented in narrative format. RESULTS: There is limited high-quality prospective data on the use of VHA in the management of acute traumatic coagulopathy in the paediatric population. While the use of fibrinogen early in major haemorrhage is becoming standard practice, there are currently no randomised prospective studies comparing fibrinogen concentrate to cryoprecipitate. CONCLUSIONS: The early identification of hypo-fibrinogenemia and acute traumatic coagulopathy in paediatric trauma using VHA testing and subsequent early fibrinogen replacement with a concentrated off the shelf product is an attractive treatment option. However, there is currently insufficient high-level evidence to support the use of fibrinogen concentrate over cryoprecipitate in the paediatric trauma population. Pilot studies currently under way will go some way to addressing this important knowledge gap, and facilitate the design of larger definitive multi-centre randomised trials.

Long-term treatment with romiplostim and treatment-free platelet responses in children with chronic immune thrombocytopenia.

Children with immune thrombocytopenia for ≥6 months completing a romiplostim study received weekly subcutaneous romiplostim (1-10 µg/kg targeting platelet counts of 50-200×109/L) in this extension to examine romiplostim's long-term safety and efficacy. Sixty-five children received romiplostim for a median of 2.6 years (range: 0.1-7.0 years). Median baseline age was 11 years (range: 3-18 years) and platelet count was 28×109/L (range: 2-458×109/L). No patient discontinued treatment for an adverse event. Median average weekly dose was 4.8 mg/kg (range: 0.1-10 mg/kg); median platelet counts remained >50×109/L, starting at week 2. Nearly all patients (94%) had ≥1 platelet response (≥50×109/L, no rescue medication in the previous 4 weeks), 72% had responded at ≥75% of visits, and 58% had responded at ≥90% of visits. Treatment-free response (platelets ≥50×109/L ≥24 weeks without immune thrombocytopenia treatment) was seen in 15 of 65 patients while withholding romiplostim doses. At onset of treatment-free response, the nine girls and six boys had a median immune thrombocytopenia duration of four years (range: 1-12 years) and had received romiplostim for two years (range: 1-6 years). At last observation, treatment-free responses lasted for a median of one year (range: 0.4-2.1 years), with 14 of 15 patients still in treatment-free response. Younger age at first dose and platelet count >200×109/L in the first four weeks were associated with treatment-free responses. In this 7-year open-label extension, three-quarters of the patients responded ≥75% of the time, and romiplostim was well tolerated, with no substantial treatment-related adverse events. Importantly, 23% of children maintained treatment-free platelet responses while withholding romiplostim and all other immune thrombocytopenia medications for ≥6 months. (Registered at clinicaltrials.gov identifier: 01071954).

Coagulation monitoring correlation with heparin dose in pediatric extracorporeal life support.

OBJECTIVES: Extracorporeal Life Support (ECLS) risks thrombotic and hemorrhagic complications. Optimal anti-coagulation monitoring is controversial. We compared coagulation tests evaluating the heparin effect in pediatric ECLS. METHODS: A retrospective study of children (<18yrs) undergoing ECLS over 12 months in a tertiary pediatric intensive care unit (PICU). Variables included anti-Factor Xa activity (anti-Xa), activated partial thromboplastin time (aPTT), activated clotting time (ACT) and thromboelastogram (TEG®6s) parameters: ratio and delta reaction (R) times (the ratio and difference, respectively, between R times in kaolin assays with and without heparinase). Test results were correlated with unfractionated heparin infusion rate (IU/kg/hr) at the time of sampling. Mean test results of each ECLS run were evaluated according to the presence/absence of complications. RESULTS: Thirty-two ECLS runs (31 patients) generated 695 data-points for correlation. PICU mortality was 22% and the thrombotic complication rate was 66%. The proportion of variation in coagulation test results explained by heparin dose was 13.3% for anti-Xa, 11.9% for ratio R time, and 9.9% for delta R time, compared with <1% for ACT and aPTT. Incorporating individual variation, age and antithrombin activity in a model with heparin dose explained less than 50% of the variation in test results. Correlation varied according to age, day of ECLS run and between individuals, with parallel dose-response lines noted between patients. Significantly lower mean anti-Xa was observed in PICU non-survivors and runs with thrombosis. CONCLUSION: Lower anti-Xa was observed in ECLS runs with complications. Although absolute results from anti-Xa and TEG6®s showed the best correlation with heparin dose, a large proportion of variation in results was unexplained by heparin, while dose response was similar between individuals. Population pharmacokinetic/pharmacodynamic modelling is required, as well as prospective trials to delineate the superior means of adjusting heparin therapy to prevent adverse clinical outcomes.

Getting stuck in the blues: persistence of mental health problems in Australia.

Do episodes of mental health (MH) problems cause future MH problems, and if yes, how strong are these dynamics? We quantify the degree of persistence in MH problems using nationally representative, longitudinal data from Australia and system generalized method of moments (GMM), and correlated random effects approaches are applied to separate true from spurious state dependence. Our results suggest only a moderate degree of persistence in MH problems when assuming that persistence is constant across the MH distribution once individual-specific heterogeneity is accounted for. However, individuals who fell once below a threshold that indicates an episode of depression are up to five times more likely to experience such a low score again a year later, indicating a strong element of state dependence in depression. Low income is a strong risk factor in state dependence for both men and women, which has important policy implications.

Childhood abuse and EEG source localization in crack cocaine dependence.

Fourteen subjects with histories of sexual and/or physical abuse in childhood and 13 matched control subjects were selected from a consecutive series of clients in residential treatment for crack cocaine dependence. Standardized low-resolution electromagnetic brain tomography (sLORETA) was used to estimate the source generators of the EEG in a cortical mask with voxel z-scores referenced to normative data at frequency intervals of 039 Hz, with nonparametric permutation to correct by randomization for the number of comparisons and the intercorrelations and variance of distribution of voxel values. Subjects with histories of abuse in childhood had significantly greater EEG power than controls in the theta frequency range (3.51-7.41 Hz), with greatest differences in the 3.90-Hz band distributed mainly in the parahippocampal, fusiform, lingual, posterior cingulate, and insular gyri. The groups did not differ significantly with regard to delta (1.56-3.12 Hz), alpha (7.81-12.48 Hz), beta (12.87-19.89 Hz), and gamma (20.28-35.10 Hz) frequency power. In excess, theta EEG power, a bandwidth of transactions among hippocampus and amygdala and paralimbic and visual association cortex, may be a correlate of childhood exposure to abuse.

Hospitalisations for sickle-cell disease in an Australian paediatric population.

AIM: Sickle-cell disease (SCD) is more prevalent in Australia due to increased migration; however, the Australian paediatric SCD population has not been previously described. This study aimed to identify the demographic features of and quantify the hospital resource utilisation in the SCD population at The Royal Children's Hospital in Victoria. METHODS: This was a retrospective chart review of SCD patients who presented to the Royal Children's Hospital over a 10.5-year period. Descriptive analyses were conducted. RESULTS: Thirty-seven SCD patients aged from 0.2 to 18.0 years (mean: 8.5 ± 4.8 years) had 535 admissions over the 10.5-year period. The population was made up of 28 homozygous sickle-cell disease, 1 sickle C disease and 8 sickle-cell beta patients from a variety of ethnic backgrounds. Admissions included 264 unplanned admissions, that is 258 admissions via the emergency department and 6 admissions via outpatients, and 271 planned admissions. Mean length of stay for unplanned admissions was 3.2 ± 2.6 days. Common diagnoses for unplanned admissions were 187 vaso-occlusive crisis (70.8%), 32 infections (12.1%) and 26 anaemic episodes (9.8%). Transfusion therapy (91.9%) accounted for the majority of planned admissions. CONCLUSIONS: Children with sickle-cell disease in an Australian setting require hospitalisation for various reasons related to disease, either unexpected complications or elective procedures. Factors affecting the provision of optimal healthcare to be explored include the multicultural demographics of the SCD population, the timely management of vaso-occlusive crises and the availability of SCD-related protocols.

A pilot study of a 12-week model of group-based exposure therapy for veterans with PTSD.

Group-based exposure therapy (GBET) is an intensive group treatment that targets posttraumatic stress disorder (PTSD) symptoms through repeated imaginal and in vivo exposure. The purpose of the present study was to assess the feasibility and acceptability of a modified 12-week course of GBET (modified from the standard 16 weeks) and to examine its effectiveness in reducing veterans' PTSD symptoms. Participants were 10 male Operation Iraqi Freedom and Vietnam-era veterans recruited from a PTSD specialty clinic at a large Veterans Affairs Medical Center. All participants were retained and demonstrated clinically significant reductions in PTSD symptoms (η(2) = .84-.87) comparable to the standard protocol. The findings from this small sample indicate that the abbreviated 12-week GBET protocol is a potentially effective treatment for PTSD.

Guidance of pharmacotherapy in a complex psychiatric case by CYP450 DNA typing.

PURPOSE: To illustrate the utility of CYP450 genotyping to guide clinical psychopharmacological treatment decisions and minimize or avoid harmful and costly adverse drug reactions (ADRs). DATA SOURCES: DNA was extracted from a whole blood sample from the case study subject and tested for CYP450 gene polymorphisms in the CLIA certified Laboratory of Personalized Health at Genomas, Inc. Clinical data were obtained from patient records and clinician observations. CONCLUSIONS: We present a case in which the ascertainment of multiple CYP450 isoenzyme deficiencies resulted in a dramatic change in psychotropic treatment approach. Shortly after making these adjustments, the patient saw a significant improvement in most of her debilitating psychiatric symptoms. IMPLICATIONS FOR PRACTICE: In complex cases, CYP450 DNA testing can guide pharmacotherapy by exposing innate hepatic metabolic deficiencies as a result of DNA polymorphism. In such cases, clinicians can favor treatments that target functional isoenzyme pathways rather than deficient or null pathways thus leading to decreased risk of ADRs and improved patient response.

Heart rate variability (HRV) and posttraumatic stress disorder (PTSD): a pilot study.

Exposure to combat experiences is associated with increased risk of developing Post Traumatic Stress Disorder. Prolonged exposure therapy and cognitive processing therapy have garnered a significant amount of empirical support for PTSD treatment; however, they are not universally effective with some patients continuing to struggle with residual PTSD symptoms. Heart rate variability (HRV) is a measure of the autonomic nervous system functioning and reflects an individual's ability to adaptively cope with stress. A pilot study was undertaken to determine if veterans with PTSD (as measured by the Clinician-Administered PTSD Scale and the PTSD Checklist) would show significantly different HRV prior to an intervention at baseline compared to controls; specifically, to determine whether the HRV among veterans with PTSD is more depressed than that among veterans without PTSD. The study also aimed at assessing the feasibility, acceptability, and potential efficacy of providing HRV biofeedback as a treatment for PTSD. The findings suggest that implementing an HRV biofeedback as a treatment for PTSD is effective, feasible, and acceptable for veterans. Veterans with combat-related PTSD displayed significantly depressed HRV as compared to subjects without PTSD. When the veterans with PTSD were randomly assigned to receive either HRV biofeedback plus treatment as usual (TAU) or just TAU, the results indicated that HRV biofeedback significantly increased the HRV while reducing symptoms of PTSD. However, the TAU had no significant effect on either HRV or symptom reduction. A larger randomized control trial to validate these findings appears warranted.

Quality of sleep in patients with posttraumatic stress disorder.

Objective. To assess the characteristics and correlates of sleep problems in patients with lifetime posttraumatic stress disorder and ongoing sleep disturbance not due to obstructive sleep apnea or other diagnosed sleep disorders.Sample. Twenty-six veterans receiving psychiatric care at the Minneapolis Veterans Affairs Medical Center in Minneapolis, Minnesota.Data collection instruments. The Pittsburgh Sleep Quality Index, sleep logs, and actigraph along with three symptom ratings scales-posttraumatic checklist, clinician-administered posttraumatic stress disorder scale, and Beck Depression Inventory-were used.Results. Univariate analysis associated three symptom complexes with poorer sleep quality: posttraumatic avoidance, posttraumatic hypervigilance, and depressive symptoms. Borderline trends also existed between worse sleep quality and more severe clinician-rated posttraumatic stress, more self-reported awakenings from sleep, and greater actigraphy-determined sleep duration. Using linear regression, only posttraumatic hypervigilance symptoms were associated with sleep quality.Conclusion. Sleep quality among posttraumatic stress disorder patients in active treatment is worse in direct relation to more severe posttraumatic hypervigilance symptoms.

Effects of arterial blood pressure on rebleeding using Celox and TraumaDEX in a porcine model of lethal femoral injury.

This study was designed to identify the systolic blood pressure (SBP) and mean arterial pressure (MAP) at which rebleeding occurs when a clot is formed by a hemostatic agent, Celox or TraumaDEX, compared with a standard dressing. Fifteen pigs (5 each) were assigned randomly to 1 of 3 groups: Celox, TraumaDEX, or standard pressure dressing as a control. In all animals, the femoral artery and vein were transected to simulate traumatic injury. Subjects were allowed to hemorrhage 1 minute before treatment. Direct pressure was held 5 minutes followed by application of elastic dressings for 30 minutes. Dressings were removed after 30 minutes, and the wound was observed for rebleeding. Animals demonstrating hemostasis received phenylephrine infusion to increase SBP in 10-mm Hg increments until SBP reached 210 mm Hg or hemorrhage recurred. There were statistically significant differences between Celox (mean SBP, 166.4 mm Hg; mean MAP, 1376 mm Hg) and the control (mean SBP, 88.25 mm Hg; mean MAP, 59.7 mm Hg), and between TraumaDEX (mean SBP, 152.2 mm Hg; mean MAP, 113.2 mm Hg) and the control (P < .05). However, no statistically significant difference existed between Celox and TraumaDEX. Celox and TraumaDEX effectively prevent rebleeding compared with standard dressing.