Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort.

BACKGROUND: Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments. METHODS: We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994-1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences. RESULTS: Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06-1.33), depression PRS (OR = 1.20, 95% CI = 1.08-1.34), family history (OR = 1.25, 95% CI = 1.11-1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07-1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk. CONCLUSION: Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.

Risky business in Georgia's wild birds: contact rates between wild birds and backyard chickens is influenced by supplemental feed.

Backyard chickens are increasingly popular, and their husbandry varies widely. How backyard chickens are housed may influence the accessibility of chicken feed and water to wild birds, and thus, the contact rates between both groups. Increased contacts have implications for pathogen transmission; for instance, Newcastle disease virus or avian influenza virus may be transmitted to and from backyard chickens from contaminated water or feed. Given this potentially increased pathogen risk to wild birds and backyard chickens, we examined which wild bird species are likely to encounter backyard chickens and their resources. We performed a supplemental feeding experiment followed by observations at three sites associated with backyard chickens in North Georgia, USA. At each site, we identified the species of wild birds that: (a) shared habitat with the chickens, (b) had a higher frequency of detection relative to other species and (c) encountered the coops. We identified 14 wild bird species that entered the coops to consume supplemental feed and were considered high-risk for pathogen transmission. Our results provide evidence that contact between wild birds and backyard chickens is frequent and more common than previously believed, which has crucial epidemiological implications for wildlife managers and backyard chicken owners.

Inactivation of MS2 bacteriophage on copper film deployed in high touch areas of a public transport system.

Although SARS-CoV-2 is primarily an airborne risk, the COVID-19 pandemic also highlighted the need for self-disinfection surfaces that could withstand the demand of high occupant densities characteristic of public transportation systems. The aim of this study was to evaluate the durability and antiviral activity of a copper film deployed for 90 days in two high touch locations within an active metropolitan bus and railcar. The antiviral efficacy of this copper film after being deployed in transit vehicles for 90 days (deployed copper film) was then compared to new (unused) copper film to determine if frequent touches and cleaning protocols could decrease the efficacy of the copper films. Deployed copper film, new copper film, and aluminium foil (positive control) coupons were inoculated with ~1 × 106 MS2 virus particles, allowed a contact time of either 5- or 10-min, and analysed for residual viral infectiousness. On both new and deployed copper films, MS2 was completely inactivated (≥5 log reduction) at both time points. These results suggest that the copper film may provide the durability demanded by high touch public spaces while maintaining the antiviral activity necessary to reduce exposure risk and viral transmission via surfaces in public transportation settings.

Enhancing clinician participation in quality improvement training: implementation and impact of an evidence-based initiative to maximise antenatal clinician participation in training regarding women's alcohol consumption during pregnancy.

BACKGROUND: There are significant challenges in ensuring sufficient clinician participation in quality improvement training. Clinician capability has been identified as a barrier to the delivery of evidence-based care. Clinician training is an effective strategy to address this barrier, however, there are significant challenges in ensuring adequate clinician participation in training. This study aimed to assess the extent of participation by antenatal clinicians in evidence-based training to address alcohol consumption during pregnancy, and to assess differences in participation by profession. METHODS: A 7-month training initiative based on six evidence-based principles was implemented in a maternity service in New South Wales, Australia. Descriptive statistics described participation in training (% attending: any training; six evidence-based principles of training; all principles). Regression analyses examined differences by profession. RESULTS: Almost all antenatal clinicians participated in some training (182/186; 98%); 69% participated in ≥1 h of training (µ = 88.2mins, SD:56.56). The proportion of clinicians participating in training that satisfied each of the six principles ranged from 35% (training from peers and experts) to 82% (training was educational and instructional). Only 7% participated in training that satisfied all principles. A significantly higher proportion of midwifery compared to medical clinicians participated in training satisfying five of the six training principles. CONCLUSIONS: A training initiative based on evidence-based principles resulted in almost all clinicians receiving some training and 69% participating in at least 1 h of training. Variability between professions suggests training needs to be tailored to such groups. Further research is required to determine possible associations with care delivery outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, No. ACTRN12617000882325 (date registered: 16/06/2017).

Syncope in a 14yo female with ventricular tachycardia; an atypical etiology.

Wide complex tachycardias are rare in the pediatric population and may be due to ventricular tachycardia, aberrant conduction or antidromic tachycardia each with multiple underlying etiologies. We present a 14 yo female in extremis with syncope at rest witnessed by her mother, found in ventricular tachycardia by EMS who challenged with IVF hydration and amiodarone. Consecutive adequate fluid challenges and antiarrhythmics in the emergency department failed requiring synchronized cardioversion for stabilization. Subsequent viral panels, imaging, genetic testing and cardiac biopsy confirmed a diagnosis of arrhythmogenic right (and left) ventricular dysplasia.

[Discharge management in pediatric and adolescent psychiatry : Expectations and realities from the parental perspective]. / Entlassmanagement in der Kinder- und Jugendpsychiatrie : Erwartungen und Realitäten aus Sicht der Eltern.

BACKGROUND: Interface management after inpatient care for mentally ill children and adolescents has been proven to be a breaking point in good transition of care between child and adolescent psychiatry, social welfare services, schools, job centre and the judicial system. Criteria for successful discharge management do not exist in child and adolescent psychiatry. Aim of the study ASpeKT was to survey parents on their perception of interface management and to derive recommendations for discharge management. METHODS: Data regarding interface management were retrieved from parents (T3, n = 124, T4, n = 81) 6 months (T3) and 12 months (T4) after discharge. RESULTS: The parents stated that accessible help after discharge from inpatient treatment is essential for stability and requires a good coordination. Parents named that they perceived helpful for successful interface management: a case manager, early round table meetings, support in returning to school, seamless access to outpatient follow-up appointments as well as information on further treatment options and contact data. CONCLUSION: From the perspective of affected families a proactive early individual and reliable care coordination by a constant contact person is essential for a good discharge management.

The kappa-opioid receptor agonist, nalfurafine, blocks acquisition of oxycodone self-administration and oxycodone's conditioned rewarding effects in male rats.

Mu-opioid receptor (MOR) agonists are highly efficacious for the treatment of pain but have significant abuse liability. Recently, we reported that nalfurafine, when combined with oxycodone at a certain ratio, reduced the reinforcing effects of oxycodone in rats while producing additive antinociceptive effects. Questions remain, however, including if the combination will function as a reinforcer in drug-naïve rats, and if the combination produces aversive effects that could explain nalfurafine's ability to reduce oxycodone self-administration? In the present study, we investigated nalfurafine's ability to reduce acquisition of oxycodone self-administration when the two were self-administered as a mixture in drug-naïve rats and nalfurafine's ability to attenuate a conditioned place preference (CPP) induced by oxycodone. In the self-administration study, male Sprague-Dawley rats self-administered intravenous injections of oxycodone (0.056 mg/kg/injection), an oxycodone/nalfurafine combination (0.056/0.0032 mg/kg/injection), or saline under fixed-ratio schedules of reinforcement for 20 days to compare rates of acquisition of drug taking. In the CPP assay, male Sprague-Dawley rats received subcutaneous injections of either saline, oxycodone (3.2 mg/kg), nalfurafine (0.18 mg/kg), or an oxycodone/nalfurafine combination at the same ratio used in the self-administration study (3.2 mg/kg/0.18 mg/kg). All subjects self-administering oxycodone alone met acquisition criteria. However, only 13% of subjects self-administering oxycodone/nalfurafine met criteria, and no subjects acquired self-administration of saline. Oxycodone, but not nalfurafine alone or the oxycodone/nalfurafine combination, produced rewarding effects in rats in the CPP test. These findings suggest that the combination of oxycodone and nalfurafine will be less habit forming in opioid-naïve patients than oxycodone alone.

Assessing the Effects of Parthenolide on Inflammation, Bone Loss, and Glial Cells within a Collagen Antibody-Induced Arthritis Mouse Model.

Rheumatoid arthritis is characterised by a chronic inflammatory response resulting in destruction of the joint and significant pain. Although a range of treatments are available to control disease activity in RA, bone destruction and joint pain exist despite suppression of inflammation. This study is aimed at assessing the effects of parthenolide (PAR) on paw inflammation, bone destruction, and pain-like behaviour in a mild collagen antibody-induced arthritis (CAIA) mouse model. CAIA was induced in BALB/c mice and treated daily with 1 mg/kg or 4 mg/kg PAR. Clinical paw inflammation was scored daily, and mechanical hypersensitivity was assessed on alternate days. At end point, bone volume and swelling in the paws were assessed using micro-CT. Paw tissue sections were assessed for inflammation and pre-/osteoclast-like cells. The lumbar spinal cord and the periaqueductal grey (PAG) and rostral ventromedulla (RVM) regions of the brain were stained for glial fibrillary acidic protein (GFAP) and ionised calcium-binding adaptor molecule 1 (IBA1) to assess for glial reactivity. Paw scores increased in CAIA mice from days 5-10 and were reduced with 1 mg/kg and 4 mg/kg PAR on days 8-10. Osteoclast-like cells on the bone surface of the radiocarpal joint and within the soft tissue of the hind paw were significantly lower following PAR treatment (p < 0.005). GFAP- and IBA1-positive cells in the PAG and RVM were significantly lower following treatment with 1 mg/kg (p < 0.0001 and p = 0.0004, respectively) and 4 mg/kg PAR (p < 0.0001 and p = 0.001, respectively). In the lumbar spinal cord, IBA1-positive cells were significantly lower in CAIA mice treated with 4 mg/kg PAR (p = 0.001). The findings indicate a suppressive effect of both low- and moderate-dose PAR on paw inflammation, osteoclast presence, and glial cell reactivity in a mild CAIA mouse model.

'Oxygen Level in a Tissue' - What Do Available Measurements Really Report?

The aim of the paper is to discuss what currently is feasible clinically to measure the level of oxygen and how that measurement can be clinically useful. Because oxygen in tissues is quite heterogeneous and all methods of measurement can only provide an average across heterogeneities at some spatial and temporal resolution, the values that are obtained may have limitations on their clinical utility. However, even if such limitations are significant, if one utilizes repeated measurements and focuses on changes in the measured levels, rather than 'absolute levels', it may be possible to obtain very useful clinical information. While these considerations are especially pertinent in cancer, they also pertain to most other types of pathology.

Clinical and Statistical Considerations when Assessing Oxygen Levels in Tumors: Illustrative Results from Clinical EPR Oximetry Studies.

The success of treatment for malignancies, especially those undergoing radiation therapy or chemotherapy, has long been recognized to depend on the degree of hypoxia in the tumor. In addition to the prognostic value of knowing the tumor's initial level of hypoxia, assessing the tumor oxygenation during standard therapy or oxygen-related treatments (such as breathing oxygen-enriched gas mixtures or taking drugs that can increase oxygen supply to tissues) can provide valuable data to improve the efficacy of treatments. A series of early clinical studies of tumors in humans are ongoing at Dartmouth and Emory using electron paramagnetic resonance (EPR) oximetry to assess tumor oxygenation, initially and over time during either natural disease progression or treatment. This approach has the potential for reaching the long-sought goal of enhancing the effectiveness of cancer therapy. In order to effectively reach this goal, we consider the validity of the practical and statistical assumptions when interpreting the measurements made in vivo for patients undergoing treatment for cancer.

Unconventional Field-Induced Spin Gap in an S=1/2 Chiral Staggered Chain.

We investigate the low-temperature magnetic properties of the molecule-based chiral spin chain [Cu(pym)(H_{2}O)_{4}]SiF_{6}·H_{2}O (pym=pyrimidine). Electron-spin resonance, magnetometry and heat capacity measurements reveal the presence of staggered g tensors, a rich low-temperature excitation spectrum, a staggered susceptibility, and a spin gap that opens on the application of a magnetic field. These phenomena are reminiscent of those previously observed in nonchiral staggered chains, which are explicable within the sine-Gordon quantum-field theory. In the present case, however, although the sine-Gordon model accounts well for the form of the temperature dependence of the heat capacity, the size of the gap and its measured linear field dependence do not fit with the sine-Gordon theory as it stands. We propose that the differences arise due to additional terms in the Hamiltonian resulting from the chiral structure of [Cu(pym)(H_{2}O)_{4}]SiF_{6}·H_{2}O, particularly a uniform Dzyaloshinskii-Moriya coupling and a fourfold periodic staggered field.

Elevated fibrinogen, von Willebrand factor, and Factor VIII confer resistance to dilutional coagulopathy and activated protein C in normal pregnant women.

BACKGROUND: Gestational changes in coagulation factor concentrations include elevations in fibrinogen, Factor VIII, and von Willebrand factor (vWF). We hypothesised that blood samples from term pregnant (TP) subjects are less prone to coagulation disturbances from haemodilution compared with those from non-pregnant (NP) females. METHODS: Blood samples were collected from 15 NP and 15 TP subjects. In vitro haemodilution with normal saline was assessed by modified Clauss fibrinogen assay, factor activity, flow-chamber assay, and thromboelastometry. The impact of human fibrinogen concentrate (hFC), cryoprecipitate, and vWF/Factor VIII (FVIII) concentrate replacement in diluted TP and NP blood was compared. Thrombin generation and activated protein C sensitivity were assessed. RESULTS: TP blood contained twice the concentrations of fibrinogen, FVIII, and vWF relative to NP blood (P<0.0001). Platelet thrombus formation (PTF) under flow was reduced by 99.2% and 69.2% in diluted NP and TP blood, respectively. Platelet thrombus formation was partially restored by adding vWF/FVIII, but not hFC or cryoprecipitate. Fibrin clot firmness approached the threshold of 10 mm in diluted NP blood, and clot firmness was effectively restored by hFC, but not by vWF/FVIII. In the presence of thrombomodulin, peak thrombin generation was decreased by 86.7% in NP plasma, but by 31.8% in TP plasma (P<0.0001 vs NP plasma), indicating reduced activated protein C sensitivity in TP plasma. Both elevated FVIII and haemodilution contributed to activated protein C insensitivity. CONCLUSIONS: Our in vitro model showed relative resistance of TP blood to dilutional coagulation changes with respect to platelet adhesion, fibrin polymerisation, and thrombin generation. Careful therapeutic monitoring for different pro-haemostatic agents in pregnant women is warranted.

Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster.

BACKGROUND: FK506-binding proteins (FKBPs) have become the subject of considerable interest in several fields, leading to the identification of several cellular and molecular pathways in which FKBPs impact prenatal development and pathogenesis of many human diseases. MAIN BODY: This analysis revealed differences between how mammalian and Drosophila FKBPs mechanisms function in relation to the immunosuppressant drugs, FK506 and rapamycin. Differences that could be used to design insect-specific pesticides. (1) Molecular phylogenetic analysis of FKBP family proteins revealed that the eight known Drosophila FKBPs share homology with the human FKBP12. This indicates a close evolutionary relationship, and possible origination from a common ancestor. (2) The known FKBPs contain FK domains, that is, a prolyl cis/trans isomerase (PPIase) domain that mediates immune suppression through inhibition of calcineurin. The dFKBP59, CG4735/Shutdown, CG1847, and CG5482 have a Tetratricopeptide receptor domain at the C-terminus, which regulates transcription and protein transportation. (3) FKBP51 and FKBP52 (dFKBP59), along with Cyclophilin 40 and protein phosphatase 5, function as Hsp90 immunophilin co-chaperones within steroid receptor-Hsp90 heterocomplexes. These immunophilins are potential drug targets in pathways associated with normal physiology and may be used to treat a variety of steroid-based diseases by targeting exocytic/endocytic cycling and vesicular trafficking. (4) By associating with presinilin, a critical component of the Notch signaling pathway, FKBP14 is a downstream effector of Notch activation at the membrane. Meanwhile, Shutdown associates with transposons in the PIWI-interacting RNA pathway, playing a crucial role in both germ cells and ovarian somas. Mutations in or silencing of dFKBPs lead to early embryonic lethality in Drosophila. Therefore, further understanding the mechanisms of FK506 and rapamycin binding to immunophilin FKBPs in endocrine, cardiovascular, and neurological function in both mammals and Drosophila would provide prospects in generating unique, insect specific therapeutics targeting the above cellular signaling pathways. CONCLUSION: This review will evaluate the functional roles of FKBP family proteins, and systematically summarize the similarities and differences between FKBP proteins in Drosophila and Mammals. Specific therapeutics targeting cellular signaling pathways will also be discussed.

Complex taxonomy of the 'brush tail' peregrine earthworm Pontoscolex corethrurus.

Pontoscolex corethrurus is the most widespread earthworm species in tropical and sub-tropical zones and one of the most studied in soil science. Although, ecological interactions of P. corethrurus with its environment are well documented, the taxonomic status of the species remains unclear. In this study, we investigated phylogenetic relationships within the genus Pontoscolex, in particular focusing on morphologically indistinguishable (i.e., cryptic) lineages. A total of 792 specimens collected from 25 different countries and islands all over the world were analyzed using two mitochondrial (COI and 16S rDNA) and two nuclear (internal transcribed spacers 2 and 28S rDNA) markers, and a total of 11 morphological characters both internal and external were investigated in all genetically characterized lineages. A large-scale multilocus sequence data matrix was also obtained for Pontoscolex spp. specimens using the Anchored Hybrid Enrichment (AHE) method. Multilocus phylogenetic and phylogenomic analyses, combined with species delimitation methods; including single locus (mPTP, ABGD) and multilocus (BPP) approaches, revealed congruent results. Four cryptic species were supported within the P. corethrurus species complex, and four potentially new species within the genus Pontoscolex. One widespread lineage (L1), within P. corethrurus complex was observed in the current population of Fritz Müller's garden where P. corethrurus was first described in 1856. Cryptic lineages were observed in sympatry at several localities. This, in combination with observed heteroplasmy in COI gene in one population raises an important question of reproductive isolation between these species.

Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior.

Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.

Factor IX from prothrombin complex concentrate augments low dose tissue factor-triggered thrombin generation in vitro.

BACKGROUND: Prothrombin complex concentrate (PCC) is increasingly used to correct acquired coagulopathy in trauma and surgery. Dosing of PCC is guided by the prothrombin time, which only reflects the onset of thrombin generation, but does not account for variations in intrinsic pathway coagulation factors, including factor IX (FIX). We hypothesised that FIX contained in PCC could strongly influence thrombin generation patterns. METHODS: Pooled normal, FIX-deficient, and warfarinised plasma were used to analyse the effects of FIX contained in PCC. PCC was evaluated at final concentrations of 0.2 and 0.4 IU ml-1 in FIX-deficient and normal plasma, and at 0.6 IU ml-1 in warfarinised plasma with elevated FVIII (1.5 IU ml-1), 40% dilution with saline, or both. The effects on thrombin generation were assessed by measuring both procoagulant and inhibitory segments. RESULTS: FIX-deficient plasma had lower peak thrombin generation [30.6 (20.5-35.8) nM vs 130.2 (107-168) nM] and endogenous thrombin potential [472 (391-532) nM vs 1096 (958-1190) nM] than normal plasma. PCC addition resulted in significant increases of peak thrombin generation [81.8 (37.3-98.3) nM] and endogenous thrombin potential [808 (472-842) nM] in FIX-deficient plasma. The combination of FVIII and PCC resulted in greater increases relative to each agent alone, restoring normal thrombin generation. After 40% dilution, adding PCC, FVIII, or both, to FIX-deficient plasma increased peak thrombin generation, and prolonged the inhibitory phase of the endogenous thrombin potential. CONCLUSIONS: FIX derived from PCC strongly enhances tissue factor-triggered thrombin generation in the presence of elevated FVIII activity. Haemodilution further enhances procoagulant effects of FIX and FVIII by slowing down inhibition of procoagulant enzymes. Dosing of PCC per prothrombin time may underestimate PCC's procoagulant potential because it does not account for intrinsic tenase or antithrombin activity.

Who's challenging who training for staff empathy towards adults with challenging behaviour: cluster randomised controlled trial.

BACKGROUND: One in five adults with intellectual disabilities (ID) known to services display challenging behaviours (CBs), and these individuals are at risk for restrictive practices and poor care. Staff attitudes may contribute to the development and/or maintenance of CBs. We investigated the effectiveness of co-produced Who's Challenging Who? training delivered by people with ID to staff. METHOD: This study involved a cluster randomised controlled trial (RCT) of Who's Challenging Who? training with follow-up at six and 20 weeks post-randomisation. PARTICIPANTS: two staff from each of 118 residential care settings for adults with ID at least one of whom displayed aggressive CB. PRIMARY OUTCOME: Self-reported Staff Empathy for people with Challenging Behaviour Questionnaire. ANALYSIS: intention to treat of all randomised settings. ISCRTN registration: ISRCTN53763600. RESULTS: 118 residential settings (including 236 staff) were randomised to either receive training (59 settings) or to receive training after a delay (59 settings). The primary analysis included data from 121 staff in 76 settings (51% of staff, 64% of settings). The adjusted mean difference on the transformed (cubed) Staff Empathy for people with Challenging Behaviour Questionnaire score at the primary end point was 1073.2 (95% CI: -938.1 to 3084.5, P = 0.296) in favour of the intervention group (effect size Cohen's d = .19). CONCLUSIONS: This is the first large-scale RCT of a co-produced training course delivered by people with ID. Findings indicated a small positive (but statistically non-significant) effect on increased staff empathy at 20 weeks, and small to moderate effects for staff reported secondary outcomes in favour of the intervention group.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Perioperative management of rare coagulation factor deficiency states in cardiac surgery.

Rare bleeding disorders (RBDs) include the hereditary deficiency of fibrinogen, factor (F)II, FV, FV + FVIII, FVII, FX, FXI or FXIII. RBDs do not confer a protective effect against atheromatous plaque formation, and thus the need for cardiovascular (CV) surgery in RBD patients is expected to increase with improved healthcare access (diagnosis and management) and longevity of the population. Clinical data regarding the management of RBDs in this setting are sparse, but the perioperative care team is obliged to gain a better understanding on available biological and pharmacological hemostatic agents. Perioperative management of RBDs in CV surgery is further complicated by heparin anticoagulation, haemodilution, and consumption of procoagulant and anticoagulant proteins associated with cardiopulmonary bypass (CPB). The aims of this review are to summarize pathophysiology of RBDs and laboratory monitoring pertinent to CV surgery, available factor replacement agents, and to provide the framework for perioperative coagulation management of RBD patients.

Assessment and validation of a defined fluid restriction protocol in the use of subcutaneous desmopressin for children with inherited bleeding disorders.

INTRODUCTION: Despite the availability of subcutaneous desmopressin (1-deamino-8-d-arginine vasopressin, SC-DDAVP) as a haemostatic agent for children with mild bleeding disorders, few publications specifically address the safety or efficacy of this mode of administration. AIM: Our aim was to assess whether a defined fluid restriction protocol was effective in preventing hyponatremia in children receiving perioperative SC-DDAVP, and to document adequate biological and clinical response in this setting. METHODS: We retrospectively analysed a cohort of children with mild bleeding disorders prescribed SC-DDAVP over a 5-year period following institution of a 'two-thirds maintenance' fluid restriction protocol. RESULTS: Sixty-nine patients received SC-DDAVP following this protocol, including 15 with mild haemophilia A, 49 with von Willebrand disease (VWD) and five with platelet storage pool disorder. In patients who underwent formal preoperative assessment a complete or partial response was observed in 28/29 with type 1 VWD and 14/15 with mild haemophilia A. Perioperative SC-DDAVP provided excellent haemostasis in all patients, with no requirement for factor concentrate or blood products. Mild asymptomatic hyponatremia was detected in seven children who received multiple doses of DDAVP (lowest sodium 129 mmol L(-1) ); however, adherence to the prescribed fluid restriction protocol was questionable in six of these cases. Symptomatic hyponatremia was not observed. CONCLUSION: Subcutaneous desmopressin was well-tolerated, with no serious side-effects observed, and good biological responses in preoperative trials. A two-thirds maintenance fluid regimen was effective at preventing symptomatic hyponatremia in our cohort, and is now the standard protocol for fluid restriction post-DDAVP administration in our centre.