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Bronwyn L Pearse, 1–3 Samantha Keogh, 4, 5 Claire M Rickard, 1, 5 Daniel J Faulke, 2 Ian Smith, 2 Douglas Wall, 3 Charles McDonald, 2 Yoke L Fung 6 1School of Nursing and Midwifery, Griffith University, Brisbane, QLD, Australia; 2Department of Anaesthesia and Perfusion, The Prince Charles Hospital, Chermside, QLD, Australia; 3Department of Cardiac Surgery, The Prince Charles Hospital, Chermside, QLD, Australia; 4School of Nursing and Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia; 5Alliance for Vascular Access Teaching and Research, Menzies Health Institute Queensland, Griffith University, Brisbane, QLD, Australia; 6School of Health and Sports Sciences, University of Sunshine Coast, Sunshine Coast, QLD, AustraliaCorrespondence: Bronwyn L PearseDepartment of Anaesthesia and Perfusion, The Prince Charles Hospital, Chermside, QLD, AustraliaTel +61 73 139 5413Fax +61 73 139 4011Email bronwyn.pearse@bigpond.comPurpose: Excessive bleeding is an acknowledged consequence of cardiac surgery, occurring in up to 10% of adult patients. This clinically important complication leads to poorer patient outcomes. Clinical practice guidelines are available to support best practice however variability in bleeding management practice and related adverse outcomes still exist. This study had two objectives: 1) to gain insight into current bleeding management practice for adult cardiac surgery in Australia and how that compared to guidelines and literature; and 2) to understand perceived difficulties clinicians face implementing improvements in bleeding management.Methods: A national cross-sectional questionnaire survey was utilized. Perspectives were sought from cardiac surgeons, cardiac anesthesiologists and perfusionists. Thirty-nine closed-ended questions focused on routine bleeding management practices to address pre and intra-operative care. One open-ended question was asked; “What would assist you to improve bleeding management with cardiac surgery patients?” Quantitative data were analysed with SPSS. Qualitative data were categorized into the domains of the Theoretical Domains Framework; the domains were then mapped to the COM-B model.Results: Survey responses from 159 Anesthesiologists, 39 cardiac surgeons and 86 perfusionists were included (response rate 37%). Four of the recommendations queried in this survey were reported as routinely adhered to < 50% of the time, 9 queried recommendations were adhered to 51– 75% of the time and 4 recommendations were routinely followed > 76% of the time.Conclusion: There is a wide variation in peri-operative bleeding management practice among cardiac anaesthesiologists, surgeons and perfusionists in Australian cardiac surgery units. Conceptualizing factors believed necessary to improve practice with the TDF and COM-B model found that bleeding management could be improved with a standardized approach including; point of care diagnostic assays, a bleeding management algorithm, access to concentrated coagulation factors, cardiac surgery specific bleeding management education, multidisciplinary team agreement and support, and an overarching national approach.Keywords: bleeding, cardiac surgery, clinical practice guidelines, multidisciplinary, theoretical domains framework, implementation

Background: Preoperative anaemia and red blood cell (RBC) transfusions are associated with poorer clinical outcomes. It is unknown whether perioperative RBC transfusions mediate the relationship between preoperative haemoglobin levels and postoperative outcomes., Methods: This was a prospective observational study among patients aged ≥50 yr undergoing elective major noncardiac surgery from four Swedish hospitals. The co-primary outcomes were 1-yr major adverse cardiovascular and cerebrovascular events (MACCEs) and all-cause mortality. The secondary outcome was a composite of 30-day mortality, MACCEs, acute kidney injury (AKI), pulmonary embolism, anastomotic leak, and postoperative infection. Mediation analyses were conducted with preoperative haemoglobin as the exposure and RBC transfusion as a mediator., Results: Among 1060 patients (mean age 70 [SD 9] yr; 472 [45%] women), 171 patients (16.1%) developed 1-yr MACCEs, and 105 patients (9.9%) died within 1 yr. Preoperative haemoglobin levels were significantly associated with both 1-yr MACCEs (b=-0.015, P=0.041) and all-cause mortality (b=-0.028, P<0.001). Volume of RBC transfusion was not directly associated with the outcomes and did not mediate the relationship between preoperative haemoglobin levels and 1-yr MACCEs (b=-0.001, P=0.451) or all-cause mortality (b=-0.002, P=0.293). For the secondary outcome, RBC transfusions had a significant mediating effect between preoperative haemoglobin and the composite 30-day outcome; however, no direct association was observed (b=0.006, P=0.554)., Conclusions: Preoperative haemoglobin levels were significantly associated with 1-yr MACCEs and all-cause mortality. This effect was not mediated by perioperative RBC transfusions. Further research is needed to confirm these findings., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: This study presents contemporary epidemiological data regarding the prevalence and severity of asthma and wheezing among children in Hong Kong, which provides an update to the results of the International Study of Asthma and Allergies in Childhood (ISAAC) conducted in 1994-1995 and 2001-2003., Methods: This cross-sectional investigation was based on the ISAAC study protocol. Responses from 1100 children aged 6 to 7 years (Primary 1-2) and 1048 children aged 13 to 14 years (Secondary 2-3) in Hong Kong between September 2020 and August 2021 were analysed. Sex differences within each age-group were assessed using Chi squared and independent t tests. Demographic information was entered into hierarchical logistic regression models to identify potential predictive factors associated with asthma severity. Annual change in prevalence was calculated via division of the prevalence by the number of years between surveys. Logistic regression modelling was conducted to identify risk factors associated with asthma severity., Results: The prevalences of current wheezing were 6.19% and 4.97% in the primary and secondary school groups, respectively. The prevalences of asthma ever were 5.55% and 6.12%, whereas those of wheezing ever were 20.38% and 12.05%, in the primary and secondary school groups, respectively., Conclusion: Asthma severity and prevalence have decreased in Hong Kong since 1994-1995. A followup study will explore the protective and risk factors contributing to these trends., Competing Interests: All authors have disclosed no conflicts of interest.

Introduction: The current study examined the contributions of comprehensive neuropsychological assessment and volumetric assessment of selected mesial temporal subregions on structural magnetic resonance imaging (MRI) to identify patients with amnestic mild cognitive impairment (aMCI) and mild probable Alzheimer's disease (AD) dementia in a memory clinic cohort., Methods: Comprehensive neuropsychological assessment and automated entorhinal, transentorhinal, and hippocampal volume measurements were conducted in 40 healthy controls, 38 patients with subjective memory symptoms, 16 patients with aMCI, 16 patients with mild probable AD dementia. Multinomial logistic regression was used to compare the neuropsychological and MRI measures., Results: Combining the neuropsychological and MRI measures improved group membership prediction over the MRI measures alone but did not improve group membership prediction over the neuropsychological measures alone., Conclusion: Comprehensive neuropsychological assessment was an important tool to evaluate cognitive impairment. The mesial temporal volumetric MRI measures contributed no diagnostic value over and above the determinations made through neuropsychological assessment., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Perioperative red blood cell transfusion is a double-edged sword for surgical patients. While transfusion of red cells can increase oxygen delivery by increasing haemoglobin levels, its impact on short- and long-term postoperative outcomes, particularly in patients undergoing elective major abdominal surgery, is unclear., Methods: We conducted a systematic review and meta-analysis on the effect of perioperative blood transfusions on postoperative outcomes in elective major abdominal surgery. PubMed, Cochrane, and Scopus databases were searched for studies with data collected between January 1, 2000 and June 6, 2020. The primary outcome was short-term mortality, including all-cause 30-day or in-hospital mortality. Secondary outcomes included long-term all-cause mortality, any morbidity, infectious complications, overall survival, and recurrence-free survival. No randomised controlled trials were found. Thirty-nine observational studies were identified, of which 37 were included in the meta-analysis., Results: Perioperative blood transfusion was associated with short-term all-cause mortality (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.89-3.91, P<0.001), long-term all-cause mortality (hazard ratio 1.35, 95% CI 1.09-1.67, P=0.007), any morbidity (OR 2.18, 95% CI 1.81-2.64, P<0.001), and infectious complications (OR 1.90, 95% CI 1.60-2.26, P<0.001). Perioperative blood transfusion remained associated with short-term mortality in the sensitivity analysis after excluding studies that did not control for preoperative anaemia (OR 2.27, 95% CI 1.59-3.24, P<0.001)., Conclusions: Perioperative blood transfusion in patients undergoing elective major abdominal surgery is associated with poorer short- and long-term postoperative outcomes. This highlights the need to implement patient blood management strategies to manage and preserve the patient's own blood and reduce the need for red blood cell transfusion., Trial Registration: PROSPERO (CRD42021254360)., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Securing an adequate blood supply relies on accurate knowledge of blood donors and donation practices. As published evidence on Asian populations is sparse, this study aims to gather up-to-date information on blood donors and donation practices in Asia to assist planning and strategy development., Materials and Methods: Ten blood collection agencies (BCAs) provided 12 months' data on donors who met eligibility criteria or were deferred, as well as details of their donation practices. Body mass index and blood volumes were calculated and analysed., Results: Data on 9,599,613 donations and 154,834 deferrals from six national and four regional BCAs revealed varied donation eligibility and collection practices. Seven used haemoglobin (Hb) criteria below the World Health Organization anaemia threshold. Seven accepted donors weighing <50 kg. Data collection on the weight and height of donors and on deferrals was inconsistent, often not routine. Deferred donors appear to weigh less, with corresponding lower estimated blood volume., Conclusion: The diversity in eligibility criteria and donation practices reflects each BCA's strategy for balancing donor health with securing an adequate blood supply. Use of lower Hb criteria substantiate their appropriateness in Asia and indicate the need to define Hb reference intervals relevant to each population. We encourage routine gathering of donor weight and height data to enable blood volume estimation and local optimization of donation volumes. Blood volume estimation formulae specific for the Asian phenotype is needed. Information from this study would be useful for tailoring donation criteria of Asian donors around the world., (© 2023 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

The current study compared the reliability of manual collateral sulcus depth and entorhinal and transentorhinal cortical volume measurements between native oriented MRI scans versus MRI scans realigned to the hippocampal long axis. Data included 10 participants with two serial 3.0T MRI scans from the Alzheimer's Disease Neuroimaging Initiative. Both collateral sulcus depth and entorhinal and transentorhinal cortical volume measurement reliability improved from the native to the hippocampal oriented scans. Standardizing scan orientation is important to optimize reliability of MRI-derived manual measurements of the entorhinal and transentorhinal cortices. In quantitative MRI studies, aligning scans to a common, normalized orientation is recommended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The current study aimed to validate entorhinal and transentorhinal cortical volumes measured by the automated segmentation tool Automatic Segmentation of Hippocampal Subfields (ASHS-T1). The study sample comprised 34 healthy controls (HCs), 37 individuals with amnestic mild cognitive impairment (aMCI), and 29 individuals with Alzheimer's disease (AD) dementia from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Entorhinal and transentorhinal cortical volumes were assessed using ASHS-T1, manual segmentation, as well as a widely used automated segmentation tool, FreeSurfer v6.0.1. Mean differences, intraclass correlation coefficients, and Bland-Altman plots were computed. ASHS-T1 tended to underestimate entorhinal and transentorhinal cortical volumes relative to manual segmentation and FreeSurfer. There was variable consistency and low agreement between ASHS-T1 and manual segmentation volumes. There was low-to-moderate consistency and low agreement between ASHS-T1 and FreeSurfer volumes. There was a trend toward higher consistency and agreement for the entorhinal cortex in the aMCI and AD groups compared to the HC group. Despite the differences in volume measurements, ASHS-T1 was sensitive to entorhinal and transentorhinal cortical atrophy in both early and late disease stages. Based on the current study, ASHS-T1 appears to be a promising tool for automated entorhinal and transentorhinal cortical volume measurement in individuals with likely underlying AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Anaemic cardiac surgery patients are at greater risk of intraoperative red blood cell transfusion. This study questions the application of the World Health Organization population-based anaemia thresholds (haemoglobin <120 g L -1 in non-pregnant females and <130 g L -1 in males) as appropriate preoperative optimisation targets for cardiac surgery., Methods: A retrospective cohort study was conducted on adults ≥18 yr old undergoing cardiopulmonary bypass surgery. Logistic regression was applied to define sex-specific preoperative haemoglobin concentrations with reduced probability of intraoperative red blood cell transfusion for cardiac surgery patients., Results: Data on 4384 male and 1676 female patients were analysed. Binarily stratified multivariable logistic regression odds of receiving intraoperative red blood cell transfusion increased in cardiac surgery patients >45 yr old (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.33-2.55), surgery urgency <30 days (OR 2.03; 95% CI 1.66-2.48), combined coronary artery bypass grafting and valve surgery, or other surgery types (OR 2.24; 95% CI 1.87-2.67), and female sex (OR 1.92; 95% CI 1.62-2.28). The odds decreased by 8.4% with each 1 g L -1 increase in preoperative haemoglobin (OR 0.92; 95% CI 0.91-0.92). Logistic regression predicted females required a preoperative haemoglobin concentration of 133 g L -1 and males 127 g L -1 to have a 15% probability of intraoperative transfusion., Conclusions: The World Health Organization female anaemia threshold of haemoglobin <120 g L -1 disproportionately disadvantages female cardiac surgery patients. A preoperative haemoglobin concentration ≥130 g L -1 in adult cardiac surgery patients would minimise their overall probability of intraoperative red blood cell transfusion to <15%., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Human neutrophil antigens (HNAs) are categorized into five systems: HNA-1 to HNA-5. Given the importance of neutrophils in immunity, we sought to create awareness of the role of HNA diagnostic services in managing immune neutropenia and transfusion-related acute lung injury. To provide health communities all around the world with access to these services, we conducted a survey to create a directory of these HNA diagnostic services., Materials and Methods: An Excel table-based survey was created to capture information on the laboratory's location and was emailed to 55 individuals with known or possible HNA investigation activity. The collected data were then summarized and analysed., Results: Of contacted laboratories, the surveys were returned from 23 (38.2%) laboratories; 17 have already established HNA diagnostic (of them 12 were regular participants of the International Granulocyte Immunobiology Workshop [ISBT-IGIW]), 4 laboratories were in the process of establishing their HNA investigation and the remaining 2 responder laboratories, did not conduct HNA investigations. In established laboratories, investigation for autoimmune neutropenia (infancies and adults) was the most frequently requested, and antibodies against HNA-1a and HNA-1b were the most commonly detected., Conclusion: The directory of survey respondents provides a resource for health professionals wanting to access HNA diagnostic services. The present study offers a comprehensive picture of HNA diagnostics (typing and serology), identifying weak points and areas for improvement for the first time. Identifying more laboratories involved in HNA diagnostics with limited access to international societies in the field will globally improve HNA diagnostics., (© 2023 Institute of Clinical Immunology and Transfusion Medicine and The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background: Studies on the relationship between childhood allergic disease and health-related quality of life (HRQOL) have mostly been confined to a single allergic condition. Therefore, a composite allergic score (CAS) was derived to assess the accumulated effect of eczema, asthma, and allergic rhinitis on HRQOL in Hong Kong schoolchildren., Methods: Parents of grade one/two or grade eight/nine schoolchildren completed a questionnaire assessing the prevalence and severity of eczema (POEM), asthma (C-ACT/ACT), and allergic rhinitis (VAS) and schoolchildren's HRQOL (PedsQL). Three rounds of recruitment were conducted. A total of 19 primary and 25 secondary schools agreed to participate., Results: Data from 1140 caregivers of grade one/two schoolchildren and 1048 grade eight/nine schoolchildren were imputed and analyzed. The proportion of female respondents were lower in grade one/two (37.7%) but higher in grade eight/nine (57.3%). 63.8% of grade one/two and 58.1% of grade eight/nine schoolchildren reported having at least one allergic disease. In general, greater disease severity was significantly associated with lower HRQOL. After controlling for age, gender, and allergic comorbidity in hierarchical regressions, CAS significantly predicted all HRQOL outcomes in both grade one/two and grade eight/nine schoolchildren. Female grade eight/nine schoolchildren reported lower HRQOL outcomes., Conclusion: Composite allergic score may be a practical tool to evaluate allergic comorbidity and the effectiveness of treatments targeting common pathological mechanisms of allergic diseases. Non-pharmaceutical approaches should be considered, especially for patients with more than one allergic disease and greater severity., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Beige adipocytes are thermogenic with high expression of uncoupling protein 1 in the white adipose tissue (WAT), accompanied by angiogenesis. Previous studies showed that Smad4 is important for angiogenesis. Here we studied whether endothelial Smad4 -mediated angiogenesis is involved in WAT beiging. Inducible knockout of endothelial cell (EC) selective Smad4 ( Smad4 iEC-KO ) was achieved by using the Smad4 Floxp/floxp and Tie2 CreERT2 mice. Beige fat induction achieved by cold or adrenergic agonist, and angiogenesis were attenuated in WAT of Smad4 iEC-KO mice, with the less proliferation of ECs and adipogenic precursors. RNA sequencing of human ECs showed that Smad4 is involved in angiogenesis-related pathways. Knockdown of SMAD4 attenuated the upregulation of VEGFA, PDGFA, and angiogenesis in vitro . Treatment of human ECs with palmitic acid-induced Smad1/5 phosphorylation and the upregulation of core endothelial genes. Our study shows that endothelial Smad4 is involved in WAT beiging through angiogenesis and the expansion of adipose precursors into beige adipocytes., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

The World Health Organization estimates that the world's population over 60 years of age will nearly double in the next 30 years. This change imposes increasing demands on health and social services with increased disease burden in older people, hereafter defined as people aged 60 years or more. An older population will have a greater incidence of cardiovascular disease partly due to higher levels of blood fibrinogen, increased levels of some coagulation factors, and increased platelet activity. These factors lead to a hypercoagulable state which can alter haemostasis, causing an imbalance in appropriate coagulation, which plays a crucial role in the development of cardiovascular diseases. These changes in haemostasis are not only affected by age but also by gender and the effects of hormones, or lack thereof in menopause for older females, ethnicity, other comorbidities, medication interactions, and overall health as we age. Another confounding factor is how we measure fibrinogen and coagulation through laboratory and point-of-care testing and how our decision-making on disease and treatment (including anticoagulation) is managed. It is known throughout life that in normal healthy individuals the levels of fibrinogen and coagulation factors change, however, reference intervals to guide diagnosis and management are based on only two life stages, paediatric, and adult ranges. There are no specific diagnostic guidelines based on reference intervals for an older population. How ageing relates to alterations in haemostasis and the impact of the disease will be discussed in this chapter. Along with the effect of anticoagulation, laboratory testing of fibrinogen and coagulation, future directions, and implications will be presented., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Automated magnetic resonance imaging (MRI) volumetry is a promising tool to evaluate regional brain volumes in dementia and especially Alzheimer's disease (AD)., Purpose: To compare automated methods and the gold standard manual segmentation in measuring regional brain volumes on MRI across healthy controls, patients with mild cognitive impairment, and patients with dementia due to AD., Study Type: Systematic review and meta-analysis., Data Sources: MEDLINE, Embase, and PsycINFO were searched through October 2021., Field Strength: 1.0 T, 1.5 T, or 3.0 T., Assessment: Two review authors independently identified studies for inclusion and extracted data. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2)., Statistical Tests: Standardized mean differences (SMD; Hedges' g) were pooled using random-effects meta-analysis with robust variance estimation. Subgroup analyses were undertaken to explore potential sources of heterogeneity. Sensitivity analyses were conducted to examine the impact of the within-study correlation between effect estimates on the meta-analysis results., Results: Seventeen studies provided sufficient data to evaluate the hippocampus, lateral ventricles, and parahippocampal gyrus. The pooled SMD for the hippocampus, lateral ventricles, and parahippocampal gyrus were 0.22 (95% CI -0.50 to 0.93), 0.12 (95% CI -0.13 to 0.37), and -0.48 (95% CI -1.37 to 0.41), respectively. For the hippocampal data, subgroup analyses suggested that the pooled SMD was invariant across clinical diagnosis and field strength. Subgroup analyses could not be conducted on the lateral ventricles data and the parahippocampal gyrus data due to insufficient data. The results were robust to the selected within-study correlation value., Data Conclusion: While automated methods are generally comparable to manual segmentation for measuring hippocampal, lateral ventricle, and parahippocampal gyrus volumes, wide 95% CIs and large heterogeneity suggest that there is substantial uncontrolled variance. Thus, automated methods may be used to measure these regions in patients with AD but should be used with caution., Evidence Level: 3 TECHNICAL EFFICACY: Stage 3., (© 2021 International Society for Magnetic Resonance in Medicine.)

Diabetic vasculopathy is a major health problem worldwide. Peripheral arterial disease (PAD), and in its severe form, critical limb ischemia is a major form of diabetic vasculopathy with limited treatment options. Existing literature suggested an important role of PPARδ in vascular homeostasis. It remains elusive for using PPARδ as a potential therapeutic target due to mostly the side effects of PPARδ agonists. To explore the roles of PPARδ in endothelial homeostasis, endothelial cell (EC) selective Ppard knockout and controlled mice were subjected to hindlimb ischemia (HLI) injury. The muscle ECs were sorted for single-cell RNA sequencing (scRNA-seq) analysis. HLI was also performed in high fat diet (HFD)-induced obese mice to examine the function of PPARδ in obese mice with delayed vascular repair. Adeno-associated virus type 1 (AAV1) carrying ICAM2 promoter to target endothelium for overexpressing PPARδ was injected into the injured muscles of normal chow- and HFD-fed obese mice before HLI surgery was performed. scRNA-seq analysis of ECs in ischemic muscles revealed a pivotal role of PPARδ in endothelial homeostasis. PPARδ expression was diminished both after HLI injury, and also in obese mice, which showed further delayed vascular repair. Endothelium-targeted delivery of PPARδ by AAV1 improved perfusion recovery, increased capillary density, restored endothelial integrity, suppressed vascular inflammation, and promoted muscle regeneration in ischemic hindlimbs of both lean and obese mice. Our study indicated the effectiveness of endothelium-targeted PPARδ overexpression for restoring functional vasculature after ischemic injury, which might be a promising option of gene therapy to treat PAD and CLI., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Transfusion-related acute lung injury (TRALI) can occur during or after a transfusion, and remains a leading cause of transfusion-associated morbidity and mortality. TRALI is caused by the transfusion of either anti-leukocyte antibodies or biological response modifiers (BRMs). Experimental evidence suggests at least six different pathways that antibody-mediated TRALI might follow: (i) two hit neutrophil activation; (ii) monocyte and neutrophil dependent; (iii) endothelial cell, neutrophil Fc receptor, platelet and neutrophil extracellular trap dependent; (iv) direct monocyte activation; (v) direct endothelial cell activation; and (vi) endothelial cell, complement and monocyte dependent. Two of these pathways (i and v) also apply to BRM-mediated TRALI. Different antibodies or BRMs might initiate different pathways. Even though six pathways are described, these might not be distinct, and might instead be interlinked or proceed concurrently. The different pathways converge upon reactive oxygen species release which damages pulmonary endothelium, precipitating fluid leakage and the clinical symptoms of TRALI. Additional pathways to the six described are likely to also contribute to TRALI pathogenesis, and this requires further investigation. This review also discusses evidence of protective mechanisms and their implications for clinical TRALI treatment. Finally, it suggests directions for future research to support the translation of these findings into strategies to prevent and treat clinical TRALI., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: This research aims to elucidate drivers of blood use in an older population, with a focus on unplanned transfusions following ED presentation., Methods: In a retrospective cohort study we examined 2015 data for ED presentations and blood use in two hospitals serving a population containing a high proportion (21%) of adults aged ≥65 years. Unplanned blood use was defined as any transfusion ≤24 h of presentation. Data were analysed by age, sex, Major Diagnostic Category, triage category and time to transfusion., Results: A total of 5294 blood components were transfused, comprising red cells (n = 3784), fresh frozen plasma (n = 657), platelets (n = 563) and cryoprecipitate (n = 290). Men aged ≥65 years were the highest users (40%, 2107 components). Unplanned transfusions accounted for 28% (n = 1057) of annual red cell use. Of 85 014 ED presentations, 494 (0.6%) were associated with unplanned red cell transfusion. Four Major Diagnostic Categories accounted for 81% (n = 853) of unplanned red cell use: gastrointestinal (n = 375), haematology (n = 267), trauma (n = 144) and cardiovascular (n = 67). Over one-fifth of unplanned transfusions (21%, n = 222 of 1057) were associated with ICD-10 codes for anaemia as a reason for presentation within the Haematology Major Diagnostic Category. Adults aged ≥65 years accounted for 62% of overall red cell use and 61% of transfusions ≤24 h of presentation. Odds of unplanned red cell transfusion increased with age, peaking at odds ratio 28.5 (95% confidence interval 14.2-57.4) in those aged 85 years and above., Conclusions: Unplanned blood use accounted for 28% of annual hospital blood consumption. Blood component use increased with age and was greatest in older men. A significant burden of anaemia treatment was identified by the ED., (© 2021 Australasian College for Emergency Medicine.)

Population dynamics are functions of several demographic processes including survival, reproduction, somatic growth, and maturation. The rates or probabilities for these processes can vary by time, by location, and by individual. These processes can co-vary and interact to varying degrees, e.g., an animal can only reproduce when it is in a particular maturation state. Population dynamics models that treat the processes as independent may yield somewhat biased or imprecise parameter estimates, as well as predictions of population abundances or densities. However, commonly used integral projection models (IPMs) typically assume independence across these demographic processes. We examine several approaches for modelling between process dependence in IPMs and include cases where the processes co-vary as a function of time (temporal variation), co-vary within each individual (individual heterogeneity), and combinations of these (temporal variation and individual heterogeneity). We compare our methods to conventional IPMs, which treat vital rates independent, using simulations and a case study of Soay sheep ( Ovis aries ). In particular, our results indicate that correlation between vital rates can moderately affect variability of some population-level statistics. Therefore, including such dependent structures is generally advisable when fitting IPMs to ascertain whether or not such between vital rate dependencies exist, which in turn can have subsequent impact on population management or life-history evolution., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: Atopic dermatitis (AD) is the most common childhood inflammatory skin problem affecting 15%-30% of children. Although AD adversely impacts the psychosocial well-being of children and their parent caregivers, parents' psychosocial well-being is seldom mentioned in most non-pharmacological education programmes. A family-based psychosocial intervention, Integrative Body-Mind-Spirit (I-BMS) intervention, is examined. This study compares the efficacy of two versions of the I-BMS intervention (one delivered to both parents and children; one delivered to parents only) with a health education active control (delivered to parents only) in promoting adaptive emotional regulation and quality of life of children with AD and their parent caregivers., Methods and Analysis: This is a three-arm, with equal randomisation, parallel randomised controlled trial. 192 parent-child dyads will be recruited through hospitals and non-governmental organisations in Hong Kong. Each dyad will complete an individual pre-group screening interview. Eligible dyads will be randomised in a ratio of 1:1:1 into one of the three arms. Each arm consists of six weekly sessions. A computer-generated list of random numbers will be used to perform randomisation. The primary outcomes are quality of life and emotional regulation. Assessments are administered at baseline, post-intervention and 6-week follow-up. Mixed factorial Analysis of Covariance (ANCOVAs) based on intention-to-treat principle will be conducted to examine the efficacy of the two I-BMS interventions. Structural equation modelling will be conducted to examine the parent-child interdependent effects of intervention., Ethics and Dissemination: Ethics approval was obtained from the Human Research Ethics Committee of the University of Hong Kong (EA2001001) and the Institutional Review Board of the Hospital Authority of Hong Kong (UW 21-400, KC/KE-20-0360/FR-2, NTEC-2021-0408). Consent will be sought from participating parents and children. Parental consent for child participants will also be obtained. Findings will be presented in peer-reviewed journals and at conferences in medical dermatology, paediatrics and social work., Trial Registration Number: ClinicalTrials.gov Registry (NCT04617977)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the blood supply contribution of older donors in five Asia Pacific regions., Background: Older people are often the largest blood user group. Thus, as the population ages blood supply needs increase. Minimum and maximum donation age criteria potentially constrain the size of the donor pool., Materials and Methods: Haemoglobin values and demographic frequency analytics (sex, age and blood type) were analysed on blood donors aged 60 years or more, from Hong Kong, Indonesia, Japan, Singapore and South Korea over 12 months., Results: Data on  434357 donations was analysed. ABO Rh(D) frequencies of older donors matched that of national frequencies. Older donors were a disproportionately smaller proportion of the total donor pool for each country. Indonesia was the only region with no maximum age limit. Median haemoglobin for older males ranged from 14.2 to 14.8 g/dl and for females 13.1 to 13.9 g/dl. The frequency of female donors was between 15% and 33% of older donors. Older donors had higher donation frequency and lower deferral rates., Conclusion: Older donors are loyal and regular donors but under-represented in all regions studied. They could help meet future blood supply needs, especially post-menopausal female donors. Studies including ferritin levels are needed to determine if upper age limits can be safely modified., (© 2021 British Blood Transfusion Society.)

Aim: To present findings from a longitudinal study on infection risk, mortality, and patient perspective of intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) treatment for patients with hypogammaglobulinemia secondary to hematological malignancy or its treatment (abbreviated as SID)., Methods: Observational study period included final year of IVIg (13 patients) and of the first 3 years of SCIg (17 patients) with SID. Data were collected on clinical outcomes from medical records and patient perception via study specific questionnaire., Results: The median age was 63 years (53-76 years), and for 82.4% of patients their hematological malignancy was in complete remission. The annual mean serum IgG trough levels remained stable over the 4 years and were 7.0 g/L (±2.77 g/L) with IVIg, and 8.0 g/L (±1.75 g/L), 8.7 g/L (±2.75 g/L), and 7.6 g/L (±2.89 g/L) (year 1, 2, and 3, respectively) with SCIg. While the annual infection rate was similar, the rate of hospitalization due to infection fluctuated, with 37%, 9%, 15%, and 32% in year 1, 2, 3, and 4 respectively. There were no systemic adverse events with IVIg or SCIg. Patients reported a strong preference for SCIg. One patient died due to progression of underlying disease and infection within the study period., Conclusion: SCIg was the preferred treatment mode over IVIg in our cohort, but both were well tolerated without any systemic adverse events in 4-year follow up. The dosage and serum IgG levels were stable throughout. However, the number of infections requiring hospitalization fluctuated. It is anticipated that these findings encourage more hospitals to offer SCIg for SID patients., (© 2021 John Wiley & Sons Australia, Ltd.)

Women with polycystic ovary syndrome (PCOS) suffer significant psychological distress, which may activate the hypothalamus-pituitary-ovary axis and further affect their physiological state. They often experience elevated levels of testosterone and triglycerides. Considering reports of psychological distress among women with PCOS, this study aimed to develop a psychosocial intervention to improve their emotional and physical health, particularly in Chinese society. This pilot study employed the Integrative Body-Mind-Spirit (I-BMS) intervention model for women with PCOS in China. After a 2 h health information session, 18 participants were randomly assigned to the I-BMS group (9) or the control group (9). The intervention group received 6 weekly, 3 h I-BMS sessions. Pre- and post-blood tests and psychosocial questionnaires were collected from all participants. Retention to treatment was high with 79.6% treatment adherence gained and an overall average of five sessions completed. Compared with the control group, depression and anxiety symptoms reduced significantly for those in the intervention group ( d = -1.24, p < 0.05 and d = -1.33, p < 0.01), their health-related quality of life improved significantly ( d = 1.02, p < 0.01) both at post-intervention and 3 month follow-up, and their testosterone and triglycerides levels reduced significantly ( d = -0.97, p < 0.001 and d = -0.41, p < 0.05) after joining the intervention. The I-BMS model is feasible and appears promising in improving psychological health, and reducing testosterone and triglyceride levels, in women with PCOS in China. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1900027606., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yin, Du, Zou, Fung, Sun, Chan and Chan.)

Background: Bleeding during cardiac surgery is a common complication that often requires the transfusion of blood products. The combination of bleeding and blood product transfusion incrementally increases adverse outcomes including infection and mortality. Following bleeding management guideline recommendations could assist with minimising risk but adherence is not high, and the cause for lack of adherence is not well understood. This study aimed to identify barriers and facilitators to practicing and implementing evidenced-based intra-operative, bleeding management in Australian cardiac surgery units., Methods: We used a qualitative descriptive design to conduct semi-structured interviews with Australian cardiac surgeons, anaesthetists and perfusionists. The Theoretical Domains Framework (TDF) was utilised to guide interviews and thematically analyse the data. Categorised data were then linked with the three key domains of the COM-B model (capability, opportunity, motivation - behaviour) to explore and understand behaviour., Results: Seventeen interviews were completed. Nine of the 14 TDF domains emerged as significant. Analysis revealed key themes to improving capability included, standardisation, monitoring, auditing and feedback of data and cross discipline training. Opportunity for change was improved with interpersonal and interdepartmental collaboration through shared goals, and more efficient and supportive processes allowing clinicians to navigate unfamiliar business and financial models of health care. Results suggest as individuals, clinicians had the motivation to make change and healthcare organisations have an obligation and a responsibility to partner with clinicians to support change and improve goal directed best practice., Conclusion: Using a theory-based approach it was possible to identify factors which may be positively or negatively influence clinicians ability to implement best practice bleeding management in Australian cardiac surgical units.

Background and Objectives: Sheep are increasingly being used as a large in vivo animal model of blood transfusion because they provide several advantages over small animals. Understanding the effects of storage duration on ovine (ov) red cell concentrates (RCCs) and how these changes compare with stored human (hu) RCCs is necessary to facilitate clinical translation of research findings., Materials and Methods: OvRCCs (n = 5) collected and processed in standard human blood collection packs, and equivalent huRCCs provided by Australian Red Cross Lifeblood (n = 5), were stored at 2-6°C for 42 days, with samples collected weekly. Haemolysis index was determined by measuring supernatant haemoglobin concentration. Biochemical parameters were evaluated using a blood gas analyser. Energy metabolites and biologically active lipids were measured using commercial assays. Osmotic fragility was determined by lysis in various saline concentrations. Extracellular vesicles were characterized by nanoparticle tracking analysis., Results: Ovine red blood cells (RBCs) are double in number, smaller in size and more fragile than human RBCs. Haematological values were unchanged throughout storage. In contrast, biochemical and metabolic values, and haemolysis index in three of the five ovRCCs exceeded huRCCs licensing criteria by day 42. Accumulation of extracellular vesicles and biologically active lipids was comparable between huRCCs and ovRCCs., Conclusion: This study documents similarities and differences in the storage lesion of ovRCCs and huRCCs. This new information will guide the design of ovine transfusion models to enhance translation of findings to human transfusion settings., (© 2020 International Society of Blood Transfusion.)

Purposes/objectives: This paper reports the comparative efficacies of integrative body-mind-spirit intervention (I-BMS) and cognitive behavioral therapy (CBT) in patient-caregiver parallel groups for Chinese patients with lung cancer. Design: Randomized controlled trial (RCT). Methods: One hundred and fifty-seven patient-caregiver dyads with no marked functional impairment were randomized into one of the two interventions with eight weekly patient-caregiver parallel groups. Assessments were conducted at baseline, within one, eight- and sixteen-weeks post-intervention. Effects of treatment group across time were analyzed by multilevel modeling. Findings: CBT led to greater reduction in emotional vulnerability than I-BMS. I-BMS resulted in greater increase in overall QoL and spiritual self-care, and more reduction in depression than CBT. Patients in both interventions experienced improvement in physical, emotional and spiritual, except social, domains of QoL. Conclusion: I-BMS was more efficacious for diverse domains of QoL, and CBT was more effective for emotional well-being, despite the relatively small between-group effect sizes. Implications for psychosocial providers/policy: (1) With the expanding repertoire of psychosocial interventions for families facing lung cancer, it has become imperative to investigate the comparative efficacies of empirically supported and culturally adapted interventions. (2) Our findings show that I-BMS was more effective for diverse domains of QoL, while CBT was more efficacious with emotional well-being, although both interventions led to significant improvements in physical, emotional and spiritual domains of patient QoL. (3) Patient-caregiver parallel groups have been shown to be effective for enhancing QoL of Chinese lung cancer patients. (4) Care professionals are encouraged to dispense interventions based on the idiosyncratic needs and preferences of the patients to maximize the treatment effects.

Reference intervals are vital for interpreting coagulation results. Current interval ranges have no upper age limit, although there is evidence that coagulation function changes with age. This study compared coagulation results from healthy people aged >60 years against adult reference intervals for routine clotting assays and thromboelastography (TEG) to determine if reference intervals are relevant to older adults.Samples from healthy blood donors aged >60 years (n=30 male, n=30 female) were tested by TEG® 6s, prothrombin time (PT), activated partial thromboplastin time (aPTT), and derived fibrinogen.All older donor-derived fibrinogen results were within the adult reference intervals, however levels were significantly higher in females. A proportion of TEG® 6s and aPTT results were not within the reference intervals. As populations around the world live longer, these findings question whether older adults require age specific coagulation reference intervals., (© 2020 by the Association of Clinical Scientists, Inc.)

Purpose: The study adopted a randomized controlled trial to compare the effect of culturally compatible psychosocial interventions on multiple aspects of quality of life (QoL) for family caregivers of lung cancer patients., Methods: 157 Chinese informal caregivers of lung cancer patients were recruited together with the family members for whom they were providing care, and randomly assigned to either integrative body-mind-spirit intervention (I-BMS) or cognitive behavioral therapy (CBT). Patient-caregiver dyads attended the same arm of intervention in separate groups for 8 weeks. Assessments of generic QoL, anxiety, depression, perceived stress, insomnia, and caregiving burden were measured before intervention (T 0 ), within 1-week (T 1 ), 8-week (T 2 ), and 16-week (T 3 ) post-intervention., Results: Adopting the intention-to-treat analysis, family caregivers in receipt of both I-BMS and CBT exhibited a statistically significant improvement in generic QoL immediately following intervention and at follow-up assessments, with moderate effect size. Improvement of insomnia was found at T 1 for both modes, which deteriorated at follow-up; both modes reduced anxiety and perceived stress at follow-up. No intervention effect was observed in depression and domains of caregiving burden. There was no significant interaction effect between intervention type and time. No main or interaction effect between sample background variables and intervention type was found to predict symptomatic changes at T 1 and T 3 ., Conclusions: Culturally attuned I-BMS and CBT exhibited equivalent effectiveness in improving psychological distress and generic QoL for family caregivers of lung cancer patients. To improve the evaluation of outcomes, future study could benefit from incorporating a usual care control.

Background: Hospital-based intravenous immunoglobulin (IVIg) treatment has been the standard treatment mode for patients with primary immunodeficiency disease (PID). With the newer home-based subcutaneous immunoglobulin (SCIg) becoming approved for use in most countries, the question arises as to whether SCIg is a cost-effective treatment mode compared to IVIg in Australia., Materials and Methods: We developed a Markov cohort simulation model with six health states: PID without infection, PID with infection treated at home or hospital, bronchiectasis without infection, bronchiectasis with infection treated at home or hospital, bronchiectasis with chronic Pseudomonas aeruginosa infection, and death, from an Australian healthcare system perspective. A 10-year time horizon with weekly cycles was chosen, and the expected costs and quality-adjusted life-years (QALYs) of the two treatment options estimated., Results: The cumulative 10-year cost per patient was 297,547 Australian dollars (A$) with IVIg and A$ 251,713 for SCIg. IVIg resulted in 5.55 QALYs and SCIg 5.57 QALYs. Thus, SCIg appears to be a cost-saving option and possibly improves QALY from the Australian healthcare system perspective (i.e., the dominant treatment option). A probabilistic sensitivity analysis showed that the SCIg option is preferred in 93.2% of simulations given willingness to pay of A$ 50,000 per QALY gained., Discussion: The results suggest that home-based SCIg is a cost-effective treatment option for patients with PID in Queensland, Australia.

Evidence-based patient blood management guidelines commonly recommend restrictive hemoglobin thresholds of 70 to 80 g/L for asymptomatic adults. However, most transfusion trials have enrolled adults across a broad age span, with few exclusive to older adults. Our recent meta-analysis of transfusion trials that focused on older adults paradoxically found lower mortality and fewer cardiac complications when these patients were managed using higher hemoglobin thresholds. We postulate that declining cardiac output with age contributes to deteriorating oxygen delivery capacity which impacts anemia-associated outcomes in older adults and propose a model to explain this age-related difference. We reviewed evidence concerning the pathophysiology of aging to explore the disparity in transfusion trial outcomes related to hemoglobin thresholds in different age groups. The literature was searched for normative cardiac output values at different ages in healthy adults. Using normative peak cardiac output data, we modeled oxygen delivery capacity in young, middle-aged, and older adults at a range of hemoglobin levels. Cardiovascular and pulmonary systems are impacted by age-related pathophysiological changes. Diminishing peak cardiac output associated with aging reduces the maximal oxygen delivery achievable under metabolic stress. Hence, at low hemoglobin levels, older adults are more susceptible to tissue hypoxia than younger adults. Our model predicts that an older adult with a hemoglobin of 100 g/L has a similar peak oxygen delivery capacity to a young adult with a hemoglobin of 70 g/L. Age-related pathophysiological changes provide some explanation as to why older adults have a lower tolerance for anemia than younger adults. This indicates the need for patient blood management hemoglobin thresholds specific to older as distinct from younger adults. The primary application of this model is in the consideration of patients rehabilitating to life outside hospital. It is important to note that pathophysiological changes associated with critical illness and major surgery are more complex than can be described in a simple model based on cardiac output and hemoglobin concentration. However, our review of oxygen transport and delivery in health and disease states allows the model to be considered in the context of treatment decisions for anemic adults in a range of hospital and community settings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Objective: Immunoglobulin replacement therapy (IRT) is often used to support patients with primary immunodeficiency disease (PID) and secondary immunodeficiency disease (SID). Home-based subcutaneous immunoglobulin (SCIg) is reported to be a cheaper and more efficient option compared to hospital-based intravenous immunoglobulin (IVIg) for PID. In contrast, there is little information on the cost-effectiveness of IRT in SID. However, patients who develop hypogammaglobulinaemia secondary to other conditions (SID) have different clinical aetiology compared to PID. This study assesses whether SCIg provides a good value-for-money treatment option in patients with secondary immunodeficiency disease (SID)., Methods: A Markov cohort simulation model with six health states was used to compare cost-effectiveness of IVIg with SCIg from a healthcare system perspective. The costs of treatment, infection and quality-adjusted life years (QALYs) for IVIg and SCIg treatment options were modelled with a time horizon of 10 years and weekly cycles. Deterministic and probabilistic sensitivity analyses were performed around key parameters., Results: The cumulative cost for IVIg was A$151 511 and for SCIg A$144 296. The QALYs with IVIg were 3·07 and with SCIg 3·51. Based on the means, SCIg is the dominant strategy with better outcomes and at lower cost. The probabilistic sensitivity analysis shows that 88·3% of the 50 000 iterations fall below the nominated willingness to pay threshold of A$50 000 per QALY. Therefore, SCIg is a cost-effective treatment option., Conclusion: For SID patients in Queensland (Australia), the home-based SCIg treatment option provides better health outcomes and cost savings., (© 2019 International Society of Blood Transfusion.)

Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock., Materials and Methods: Twenty-one adult female sheep were randomly divided into no endotoxemia (n = 5) or endotoxemia groups (n = 16) with an escalating dose of lipopolysaccharide (LPS) up to 4 μg/kg/h administered to achieve a mean arterial pressure below 60 mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n = 8) or a 0.9% saline bolus (40 mL/kg over 60 min) (n = 8). No endotoxemia, saline only animals (n = 5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65 mm Hg in all the groups., Results: Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001)., Conclusions: Endotoxemia impairs secondary haemostasis and induces changes in the intrinsic, extrinsic and anti-coagulant pathways. These changes to haemostasis are exacerbated following resuscitation with 0.9% saline, a commonly used crystalloid in clinical settings., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Anaemia in hip fracture patients has been associated with increased risk of allogenic blood transfusion (ABT), poorer functional outcomes and increased mortality. Few studies have reported the prevalence of anaemia on admission or its progression prior to surgery in this cohort. We aimed to measure the prevalence of anaemia on admission in older persons who sustain a hip fracture, identify if anaemia develops or progresses prior to surgery, and to report associations with outcome., Methods: A retrospective, observational study was undertaken in a regional hospital. All patients aged 60 and over, admitted with a primary hip fracture resulting from a simple fall, in the 12 months of 2014 were included. The World Health Organization (WHO) definition of anaemia was used. Pathology databases and clinical records were reviewed to collect data. Repeated measures ANOVA's were used to quantify the progression of anaemia prior to surgery, and Chi square test were used to report associations with outcome variables., Results: Two hundred sixty-one patients were identified, median age was 81 years. There were twice as many females as males and just over half the sample had extracapsular fractures. Anaemia was present on admission in 45% (n = 117), highest incidence of anaemia occurred in males 52.0% (n = 39), extracapsular fractures 41.9% (n = 78) and those aged over 80 years 49.7% (n = 91). Progression of anaemia prior to surgery was significant in all groups (p < 0.05), with the greatest reduction seen in extracapsular fractures. Pre-surgery reduction in Hb was recorded in 82.3% of patients between admission and day 1, and in 71.4% between admission and day 2. There was significant association between anaemia on admission and PRBC transfusion (p < 0.05), in hospital mortality (p < 0.05) however no association with the use of antiplatelet or anticoagulant medication, nor LOS., Conclusions: The findings demonstrate that pre-surgical anaemia in older hip fracture patients is associated with a PRBC transfusion and increased hospital mortality. Importantly, it also identified that patients continue to bleed after admission, leading to the development of or worsening anaemia. Thus, identification anaemia in the pre-surgical period provides an opportunity for treatment to avoid transfusions and improve patient outcomes.

Structural neuroimaging is a useful non-invasive biomarker commonly employed to evaluate the integrity of mesial temporal lobe structures that are typically compromised in Alzheimer's disease. Advances in quantitative neuroimaging have permitted the development of automated segmentation protocols (e.g., FreeSurfer) with significantly increased efficiency compared to earlier manual techniques. While these protocols have been found to be suitable for large-scale, multi-site research studies, we were interested in assessing the practical utility and reliability of automated FreeSurfer protocols compared to manual volumetry on routinely acquired clinical scans. Independent validation studies with newer automated segmentation protocols are scarce. Two FreeSurfer protocols for each of two regions of interest-the hippocampus and entorhinal cortex-were compared against manual volumetry. High reliability and agreement was found between FreeSurfer and manual hippocampal protocols, however, there was lower reliability and agreement between FreeSurfer and manual entorhinal protocols. Although based on a the relatively small sample of subjects drawn from a memory clinic (n = 27), our study findings suggest further refinements to improve measurement error and most accurately depict true regional brain volumes using automated segmentation protocols are required, especially for non-hippocampal mesial temporal structures, to achieve maximal utility for routine clinical evaluations.

Background: Based on the cognitive theory, anxiety arising from the awareness of death and dying may activate dysfunctional attitudes, which may then reduce quality of life. This study examined the interdependence and the mediating role of dysfunctional attitudes on the relationship between death anxiety and quality of life among patients with lung cancer and their caregivers., Methods: From March 2016 to April 2017, 173 pairs of patients and their caregivers enrolled in a randomized controlled trial of psychosocial support. Using the baseline data, actor-partner interdependence modeling was used to analyze the relationships among death anxiety, dysfunctional attitudes, and quality of life., Results: In patients, death anxiety was related to dependency (β = .51) and self-control (β = -.37); achievement (β = -.21) and self-control (β = .34) were related to quality of life. Among caregivers, death anxiety was related to all 3 dysfunctional attitudes of their own (βs = .23 to.32); dependency (β = -.22) was associated with quality of life. Caregiver quality of life was also associated with patient self-control (β = .22) and achievement (β = -.18). Patient self-control mediated the links between patient death anxiety with both patient and caregiver quality of life. The relationship between death anxiety and quality of life was mediated by dependency in caregivers., Discussion: Death anxiety influences dysfunctional attitudes and quality of life of both patients and caregivers. Our results support the relevance of dysfunctional attitudes in understanding the impact of death anxiety and underscore the need for parallel psychosocial interventions., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Guidelines for patient blood management recommend restrictive transfusion practice for most adult patients. These guidelines are supported by evidence from randomised controlled trials (RCTs); however, one of the patient groups not explicitly examined in these studies is the geriatric population. We examined RCTs relevant to transfusion outcomes in older patients. Our aim was to determine whether special guidelines are warranted for geriatric patients, recognising the different pathophysiological characteristics of this group., Methods: For this systematic review and meta-analysis, we searched PubMed, Scopus, and the Cochrane Library databases from their inception to May 5, 2017, for evidence relating to transfusion outcomes in adults aged 65 years and older. This criterion was widened to include RCTs where a substantial proportion of the study population was older than 65 years. We also included study populations of all clinical settings, and did not limit the search by date, language, or study type. For articles not in English, only available translations of the abstracts were reviewed. Studies were excluded if they did not specify age. Observational studies and duplicate patient and outcome data from studies that generated multiple publications were also excluded. We screened bibliographies of retrieved articles for additional publications. We analysed data extracted from published RCTs comparing restrictive and liberal transfusion strategies in older adults. We generated fixed effects risk ratios (RR) for pooled study data using the Mantel-Haenszel method. Primary outcomes were 30-day and 90-day mortality events for patients enrolled in restrictive and liberal transfusion study groups. We included intention-to-treat outcome data in the meta-analysis when available, otherwise we used per-protocol outcome data., Findings: 686 articles were identified by the search, and a further 37 by the snowball approach. Of these articles, 13 eligible papers described findings from nine RCTs (five trials investigating orthopaedic surgery, three cardiac surgery, and one oncology surgery; including 5780 patients). The risk of 30-day mortality was higher in older patients who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (risk ratio [RR] 1·36, 95% CI 1·05-1·74; p=0·017). The risk of 90-day mortality was also higher in those who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (RR 1·45, 95% CI 1·05-1·98; p=0·022)., Interpretation: Liberal transfusion strategies might produce better outcomes in geriatric patients than restrictive transfusion strategies. This outcome contradicts current restrictive transfusion approaches. Population ageing will challenge resources globally, and this finding has implications for blood supply and demand, and optimal care of older adults. Further research is needed to formulate evidence-based transfusion practice across clinical specialties specific to the geriatric population, and to examine resource effects., Funding: Australia's National Blood Authority., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO., Objective: To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient., Design, Participants and Intervention: An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours. An in vivo ovine model of ECMO was used to describe the population pharmacokinetic properties of ciprofloxacin in three different groups of sheep, and to investigate sources of pharmacokinetic variability. In the final phase, data from a 39-year-old critically ill man was used to validate the findings from the ovine pharmacokinetic model., Results: In the ex vivo model of ECMO circuits, the median concentrations of ciprofloxacin at baseline and at 24 hours after ciprofloxacin infusion were similar. The time course of ciprofloxacin in the in vivo ovine on ECMO model was adequately described by a two-compartment model. The final population primary parameter mean estimates were: clearance (CL), 0.21 L/kg/h (SD, 0.09 L/kg/h) and volume of distribution (V d ), 0.84 L/kg (SD, 0.12 L/kg). In the critically ill ECMO patient, the primary pharmacokinetic parameter estimates were: CL, 0.15 L/kg/h and V d , 0.99 L/kg., Conclusions: We provide preliminary evidence that ciprofloxacin dosing in ECMO patients should remain in line with the recommended dosing strategies for critically ill patients not receiving ECMO.

Background: Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of cardiopulmonary failure that is refractory to conventional medical and surgical therapies. The major problems clinicians face are bleeding and clotting, which can occur simultaneously. To discern the impact of pulmonary injury and ECMO on the host's haemostatic response, we developed an ovine model of smoke-induced acute lung injury (S-ALI) and ECMO. The aims of this study were to determine if the ECMO circuit itself altered haemostasis and if this was augmented in a host with pulmonary injury., Methods: Twenty-seven South African meat merino/Border Leicester Cross ewes underwent instrumentation. Animals received either sham injury (n = 12) or S-ALI (n = 15). Control animal groups consisted of healthy controls (ventilation only for 24 h) (n = 4), ECMO controls (ECMO only for 24 h) (n = 8) and S-ALI controls (S-ALI but no ECMO for 24 h) (n = 7). The test group comprised S-ALI sheep placed on ECMO (S-ALI + ECMO for 24 h) (n = 8). Serial blood samples were taken for rotational thromboelastometry, platelet aggregometry and routine coagulation laboratory tests. Animals were continuously monitored for haemodynamic, fluid and electrolyte balances and temperature. Pressure-controlled intermittent mandatory ventilation was used, and mean arterial pressure was augmented by protocolised use of pressors, inotropes and balanced fluid resuscitation to maintain mean arterial pressure >65 mmHg., Results: Rotational thromboelastometry, platelet aggregometry and routine coagulation laboratory tests demonstrated that S-ALI and ECMO independently induced changes to platelet function, delayed clot formation and reduced clot firmness. This effect was augmented with the combination of S-ALI and ECMO, with evidence of increased collagen-induced platelet aggregation as well as changes in factor VIII (FVIII), factor XII and fibrinogen levels., Conclusions: The introduction of an ECMO circuit itself increases collagen-induced platelet aggregation, decreases FVIII and von Willebrand factor, and induces a transient decrease in fibrinogen levels and function in the first 24 h. These changes to haemostasis are amplified when a host with a pre-existing pulmonary injury is placed on ECMO. Because patients are often on ECMO for extended periods, longer-duration studies are required to characterise ECMO-induced haemostatic changes over the long term. The utility of point-of-care tests for guiding haemostatic management during ECMO also warrants further exploration.

Immunoglobulin replacement therapy (IRT) has an important role in minimizing infections and improving the health-related quality of life (HRQoL) in patients with immunodeficiency, who would otherwise experience recurrent infections. These plasma-derived products are available as intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg). The global demand for these products is growing rapidly and has placed pressure on supply. Some malignancies and their treatment (as well as other medical therapies) can lead to secondary hypogammaglobulinemia or secondary immunodeficiency (SID) requiring IRT. Although IVIg use in this cohort has well-established therapeutic benefits, little is known about SCIg use. A literature search in July 2015 found only 7 published articles on SCIg use. These articles found that both IRT modes had equivalent efficacy in regard to reduction of bacterial infections. In addition, SCIg was reported to produce higher serum IgG trough levels compared with IVIg on equivalent dosage with the added benefit of fewer adverse effects. Patient HRQoL reports demonstrate preference for SCIg because of reduced adverse effects and hospital visits. There are no health economic models published on SCIg use in SID, but models on primary immunodeficiency disease and IRT conclude that SCIg provided greater economic benefits than IVIg. The findings of this small number of reports suggest that SCIg therapy for patients with SID is likely to be beneficial for both the patient and health care providers. To substantiate wider use of SCIg in SID, larger and more detailed studies are needed to accurately quantify the effectiveness of SCIg., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for patients with severe refractory cardiorespiratory failure. Exposure to the ECMO circuit is thought to trigger/exacerbate inflammation. Determining whether inflammation is the result of the patients' underlying pathologies or the ECMO circuit is difficult. To discern how different insults contribute to the inflammatory response, we developed an ovine model of lung injury and ECMO to investigate the impact of smoke-induced lung injury and ECMO in isolation and cumulatively on pulmonary and circulating inflammatory cells, cytokines, and tissue remodeling. Sheep receiving either smoke-induced acute lung injury (S-ALI) or sham injury were placed on veno-venous (VV) ECMO lasting either 2 or 24 h, with controls receiving conventional ventilation only. Lung tissue, bronchoalveolar fluid, and plasma were analyzed by RT-PCR, immunohistochemical staining, and zymography to assess inflammatory cells, cytokines, and matrix metalloproteinases. Pulmonary compliance decreased in sheep with S-ALI placed on ECMO with increased numbers of infiltrating neutrophils, monocytes, and alveolar macrophages compared with controls. Infiltration of neutrophils was also observed with S-ALI alone. RT-PCR studies showed higher expression of matrix metalloproteinases 2 and 9 in S-ALI plus ECMO, whereas IL-6 was elevated at 2 h. Zymography revealed higher levels of matrix metalloproteinase 2. Circulating plasma levels of IL-6 were elevated 1-2 h after commencement of ECMO alone. These data show that the inflammatory response is enhanced when a host with preexisting pulmonary injury is placed on ECMO, with increased infiltration of neutrophils and macrophages, the release of inflammatory cytokines, and upregulation of matrix metalloproteinases., (Copyright © 2016 the American Physiological Society.)