Study of the impact of the vascular systemic risk factors on peripapillary vascular density by optical coherence tomography angiography.

BACKGROUND: The focus of therapeutic tools in glaucoma has been mainly to control of intraocular pressure. Recently there has been a growing interest in investigating the relationship of vascular risk factors in the development of glaucoma. The aim of this study was to assess the association between systemic arterial hypertension, diabetes mellitus and hypercholesterolemia, and peripapillary vascularization measured by Optical Coherence Tomography Angiography (OCTA) in glaucoma and healthy subjects. METHODS: In this unicenter, observational, cross-sectional study, 212 subjects, 118 glaucoma patients and 94 controls were consecutively recruited. Of these, 86 participants were excluded due to poor OCTA image quality. Therefore, 146 subjects were included in the final analysis, 74 glaucoma patients and 72 controls. Using a linear regression model, with 95% confidence and 80% statistical power, the effect of vascular risk factors on OCTA parameters in the 146 subjects included in the final analysis was studied. RESULTS: No significant impact of vascular risk factors on OCTA measurements was found. Diabetic patients tended to show a lower peripapillary perfusion vascular density than subjects without diabetes (ß 0.016, 95%CI 0.003;0.030, p 0.016). Similarly, hypercholesterolemia patients appeared to show less peripapillary flow index than non-hypercholesterolaemic patients (ß 0.029, 95%CI 0.013;0.046, p 0.001). Glaucoma patients had 0.02% lower peripapillary perfusion vascular density (ß 0.020, 95% CI 0.011;0.029, p < 0.001), 0.04% lower peripapillary flow index (ß 0.036, 95%CI 0.022;0.051, p < 0.001) and 9.62% thinner retinal nerve fibre layer (ß 9.619, 95%CI 5.495;13.744, p < 0.001). CONCLUSIONS: In conclusion glaucoma has greater effect on peripapillary vascular density parameters than any of the vascular risk factors analyzed. KEY MESSAGES: What is known: • Vascular disfunction plays an important role in the development of glaucoma. • Optical coherence tomography angiography makes it possible to assess the retinal microvasculature and the role that its alterations could have in the development of glaucoma. WHAT IS NEW: • Decrease of the peripapillary microcirculation seems to be more related to the increase in intraocular pressure and the glaucoma itself than to the presence of cardiovascular risk factors. • The effect of having diabetes, systemic arterial hypertension or hypercholesterolaemia on vascular parameters or nerve fibre layer thickness was low. • There was also no relevant impact of the systemic medication used for these diseases on the peripapillary vascular parameters studied or on nerve fibre layer thickness.

Corrigendum to "Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) trial: Study protocol and statistical analysis plan" [Crit Care Resuscit 25 (2023) 118-125].

[This corrects the article DOI: 10.1016/j.ccrj.2023.06.001.].

Experiences and impact of a rural Australian high-risk foot service: A multiple-methods study.

OBJECTIVE: Most podiatry-led high-risk foot services (HRFS) in Australia are located in metropolitan areas or large regional centres. In rural areas, where there are limited specialist services, individuals with diabetes-related foot ulceration are more likely to undergo amputation. This study aimed to explore clinicians' perceptions of a recently implemented HRFS in rural New South Wales, Australia, and compare trends of amputation and hospitalisation prior to and post-implementation of the service. SETTING: Rural HRFS in Tamworth, New South Wales, Australia. PARTICIPANTS: Health professionals working within the HRFS were recruited to participate. DESIGN: This was a multiple-methods study. For the qualitative arm, semi-structured interviews were conducted, which were analysed using a reflexive thematic approach. The quantitative arm of the study utilised a retrospective analytic design which applied an interrupted time series to compare amputation and hospitalisation trends pre- and post-implementation of the HRFS utilising diagnostic and procedural ICD codes. RESULTS: The qualitative arm of the study derived three themes: (1) navigating the divide, (2) rural community and rural challenges and (3) professional identity. Results of the interrupted time series indicate that there was a downward trend in major amputations following implementation of the HRFS; however, this was not statistically significant. CONCLUSION: Clinicians were aware of the inequity in DFD outcomes between rural and metropolitan areas and were committed to improving outcomes, particularly with respect to First Nations peoples. Future research will explore service use and amputation rates in the longer term to further evaluate this specialised multidisciplinary care in a rural community.

TARGET: A Phase II, Open-Label, Single-Arm Study of 5-Year Adjuvant Osimertinib in Completely Resected EGFR-Mutated Stage II to IIIB NSCLC Post Complete Surgical Resection.

INTRODUCTION: Osimertinib is a central nervous system (CNS)-active, third generation, irreversible, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations, with demonstrated efficacy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We present the rationale and design for TARGET (NCT05526755), which will evaluate the efficacy and safety of 5 years of adjuvant osimertinib in patients with completely resected EGFRm stage II to IIIB NSCLC. MATERIALS AND METHODS: TARGET is a phase II, multinational, open-label, single-arm study. Adults aged ≥18 years (Taiwan ≥20 years), with resected stage II to IIIB NSCLC are eligible; prior adjuvant chemotherapy is allowed. Eligible patients must have locally confirmed common (exon 19 deletion or L858R) or uncommon (G719X, L861Q, and/or S768I) EGFR-TKI sensitizing mutations, alone or in combination. Patients will receive osimertinib 80 mg once daily for 5 years or until disease recurrence, discontinuation or death. The primary endpoint is investigator-assessed disease-free survival (DFS) at 5 years (common EGFR mutations cohort). Secondary endpoints include: investigator-assessed DFS at 3 and 4 years; overall survival at 3, 4, and 5 years (common EGFR mutations cohort); DFS at 3, 4, and 5 years (uncommon EGFR mutations cohort); safety and tolerability, type of recurrence and CNS metastases (both cohorts). Exploratory endpoints include: tissue/plasma concordance; analysis of circulating molecules in plasma samples using different profiling approaches to detect minimal residual disease; incidence and change over time of incidental pulmonary nodules. RESULTS: TARGET is currently recruiting, and completion is expected in 2029.

Technical development and feasibility of a reusable vest to integrate cardiovascular magnetic resonance with electrocardiographic imaging.

BACKGROUND: Electrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo. METHODS: CMR was prospectively performed at 3T on participants after collecting surface potentials using the locally designed and fabricated 256-lead ECGI vest. Epicardial maps were reconstructed to generate local EP parameters such as activation time (AT), repolarization time (RT) and activation recovery intervals (ARI). 20 intra- and inter-observer and 8 scan re-scan repeatability tests. RESULTS: 77 participants were recruited: 27 young healthy volunteers (HV, 38.9 ± 8.5 years, 35% male) and 50 older persons (77.0 ± 0.1 years, 52% male). CMR-ECGI was achieved in all participants using the same reusable, washable vest without complications. Intra- and inter-observer variability was low (correlation coefficients [rs] across unipolar electrograms = 0.99 and 0.98 respectively) and scan re-scan repeatability was high (rs between 0.81 and 0.93). Compared to young HV, older persons had significantly longer RT (296.8 vs 289.3 ms, p = 0.002), ARI (249.8 vs 235.1 ms, p = 0.002) and local gradients of AT, RT and ARI (0.40 vs 0.34 ms/mm, p = 0,01; 0.92 vs 0.77 ms/mm, p = 0.03; and 1.12 vs 0.92 ms/mm, p = 0.01 respectively). CONCLUSION: Our high-throughput CMR-ECGI solution is feasible and shows good reproducibility in younger and older participants. This new technology is now scalable for high throughput research to provide novel insights into arrhythmogenesis and potentially pave the way for more personalised risk stratification. CLINICAL TRIAL REGISTRATION: Title: Multimorbidity Life-Course Approach to Myocardial Health-A Cardiac Sub-Study of the MRC National Survey of Health and Development (NSHD) (MyoFit46). National Clinical Trials (NCT) number: NCT05455125. URL: https://clinicaltrials.gov/ct2/show/NCT05455125?term=MyoFit&draw=2&rank=1.

Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial: Study Protocol and Statistical Analysis Plan.

Introduction: Critically ill patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) are at risk of developing severe arterial hyperoxia, which has been associated with increased mortality. Lower saturation targets in this population may lead to deleterious episodes of severe hypoxia. This manuscript describes the protocol and statistical analysis plan for the Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial. Design: The BLENDER trial is a pragmatic, multicentre, registry-embedded, randomised clinical trial., registered at ClinicalTrials.gov (NCT03841084) and approved by The Alfred Hospital Ethics Committee project ID HREC/50486/Alfred-2019. Participants and setting: Patients supported by VA ECMO for cardiogenic shock or cardiac arrest who are enrolled in the Australian national ECMO registry. Intervention: The study compares a conservative oxygenation strategy (target arterial saturations 92-96%) with a liberal oxygenation strategy (target 97-100%). Main Outcome Measures: The primary outcome is the number of intensive care unit (ICU)-free days for patients alive at day 60. Secondary outcomes include duration of mechanical ventilation, ICU and hospital mortality, the number of hypoxic episodes, neurocognitive outcomes, and health economic analyses. The 300-patient sample size enables us to detect a 3-day difference in ICU-free days at day 60, assuming a mean ICU-free days of 11 days, with a risk of type 1 error of 5% and power of 80%. Data will be analysed according to a predefined analysis plan. Findings will be disseminated in peer-reviewed publications. Conclusions: This paper details the protocol and statistical analysis plan for the BLENDER trial, a registry-embedded, multicentre interventional trial comparing liberal and conservative oxygenation strategies in VA ECMO.

Bioprinted cancer-stromalin-vitromodels in a decellularized ECM-based bioink exhibit progressive remodeling and maturation.

Constant matrix remodeling and cellular heterogeneity in cancer are key contributors to its development and can profoundly alter treatment efficacy. Developingin-vitromodels containing relevant features that can recapitulate these aspects of the tumor microenvironment and that are well characterized can circumvent the limitations of conventional 2D cultures and animal models. Automated fabrication methods combined with biomimetic biomaterials have provided the opportunity to create platforms that can potentially incorporate a heterogeneous population of cells in a 3D environment that allows cell-cell and cell-ECM interactions with reproducibility. This study used 3D extrusion bioprinting and a composite bioink containing a reinforced decellularized extracellular matrix (ECM) hydrogel to fabricate a head and neck cancerin-vitromodel. The constituents of this model included fibroblasts and active ECM proteins to represent the stroma, along with HNSCC cells to represent the tumor component. The topographical characterization of the bioink showed a fibrous network with nanometer-sized pores. After cell encapsulation and model fabrication, we observed spheroid development and growth over time with cancer cells in the core and fibroblasts in the periphery. Our model is compatible with matrix metalloproteinase (MMP) quantification techniques and showed significant differences in the presence of MMP-9 and MMP-10 compared to the control groups. This characterized model is proposed as a tool for further translational and drug discovery applications since it provides a biomimetic scenario that allows the study of the tumor microenvironmentin-vitrousing nondestructive longitudinal monitoring over time.

Scalable single-mode surface-emitting laser via open-Dirac singularities.

Single-aperture cavities are a key component of lasers that are instrumental for the amplification and emission of a single light mode. However, the appearance of high-order transverse modes as the size of the cavities increases has frustrated efforts to scale-up cavities while preserving single-mode operation since the invention of the laser six decades ago1-8. A suitable physical mechanism that allows single-mode lasing irrespective of the cavity size-a 'scale invariant' cavity or laser-has not been identified yet. Here we propose and demonstrate experimentally that open-Dirac electromagnetic cavities with linear dispersion-which in our devices are realized by a truncated photonic crystal arranged in a hexagonal pattern-exhibit unconventional scaling of losses in reciprocal space, leading to single-mode lasing that is maintained as the cavity is scaled up in size. The physical origin of this phenomenon lies in the convergence of the complex part of the free spectral range in open-Dirac cavities towards a constant governed by the loss rates of distinct Bloch bands, whereas for common cavities it converges to zero as the size grows, leading to inevitable multimode emission. An unconventional flat-envelope fundamental mode locks all unit cells in the cavity in phase, leading to single-mode lasing. We name such sources Berkeley surface-emitting lasers (BerkSELs) and demonstrate that their far-field corresponds to a topological singularity of charge two, in agreement with our theory. Open-Dirac cavities unlock avenues for light-matter interaction and cavity quantum electrodynamics.

Dermatofibrosarcoma Protuberans Recurrence After Wide Local Excision Versus Mohs Micrographic Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Local recurrence (LR) rates of dermatofibrosarcoma protuberans (DFSP) treated with different surgical modalities are unknown. OBJECTIVE: To evaluate the differences in LR rates of DFSP treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: Pertinent studies of DFSP treated with either WLE or MMS were identified through a search of multiple databases, including Ovid MEDLINE (1946-2018), Embase (1988-2018), Web of Science (1975-2018), and Scopus (1970-2018). Comparative 2-arm and noncomparative single-arm studies were assessed through meta-analyses. RESULTS: Of the 517 studies identified, 88 met inclusion criteria (12 comparative studies; 76 single-arm studies). In the 12 comparative studies, 352 patients with DFSP underwent MMS and 777 patients with DFSP underwent WLE. The LR rate was 1.7% after MMS and 3.7% after WLE (odds ratio, 1.549; 95% CI, 0.710-3.381; p = .27). In the 76 noncomparative studies, 980 patients underwent MMS (LR rate, 1.5%; 95% CI, 0.9%-2.1%; p < .001), and 2,215 patients underwent WLE (LR rate, 9.4%; 95% CI, 7.5%-11.3%; p < .001). CONCLUSION: The LR rate of DFSP in patients treated with MMS is lower than in patients treated with WLE. Because of high rates of postoperative DFSP LR, MMS should be strongly considered when available.

Self-Report Measures of Procrastination Exhibit Inconsistent Concurrent Validity, Predictive Validity, and Psychometric Properties.

Procrastination is a chronic and widespread problem; however, emerging work raises questions regarding the strength of the relationship between self-reported procrastination and behavioral measures of task engagement. This study assessed the internal reliability, concurrent validity, predictive validity, and psychometric properties of 10 self-report procrastination assessments using responses collected from 242 students. Participants' scores on each self-report instrument were compared to each other using correlations and cluster analysis. Lasso estimation was used to test the self-report scores' ability to predict two behavioral measures of delay (days to study completion; pacing style). The self-report instruments exhibited strong internal reliability and moderate levels of concurrent validity. Some self-report measures were predictive of days to study completion. No self-report measures were predictive of deadline action pacing, the pacing style most commonly associated with procrastination. Many of the self-report measures of procrastination exhibited poor fit. These results suggest that researchers should exercise caution in selecting self-report measures and that further study is necessary to determine the factors that drive misalignment between self-reports and behavioral measures of delay.

Overview of Dizziness in Practice.

The evaluation of dizziness as a chief complaint can be exceptionally challenging to otolaryngologists. The critical piece in evaluating dizzy patients is to have a plan for how to screen and schedule, how to gather data, and to develop a workflow for testing that allows clinical efficiency. This article provides an overview of evidence-based practices on how to screen dizzy patients before being scheduled, how to efficiently move patients through the otolaryngologist's clinic, and strategies for managing a dizzy practice.

Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes.

Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counseling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms.

An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases.

INTRODUCTION: The neurovascular unit (NVU) - the interaction between the neurons and the cerebrovasculature - is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently no in vitro 3-dimensional (3D) perfusible model of the human cortical arterial NVU. METHOD: We used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries. RESULTS: This system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It reproduces key characteristics of cortical neurons and astrocytes and enables formation of a selective and functional endothelial barrier. We provide proof-of-principle data showing that this in vitro human arterial NVU may be suitable to study neurovascular components of neurodegenerative diseases such as Alzheimer's disease (AD), as endogenously produced phosphorylated tau and beta-amyloid accumulate in the model over time. Finally, neuronal and glial fluid biomarkers relevant to neurodegenerative diseases are measurable in our arterial NVU model. CONCLUSION: This model is a suitable research tool to investigate arterial NVU functions in healthy and disease states. Further, the design of the platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses.

Enhancing hospitality business performance: The role of entrepreneurial orientation and networking ties in a dynamic environment.

Utilizing a sample of 192 hospitality firms, this study investigates the moderating role of a dynamic environment, coupled with business and social networking ties and technology resources, on the relationship between entrepreneurial orientation and organizational performance in hospitality firms. This research is novel in that we adopt business network ties and social network ties as two moderating variables along with technology resources between entrepreneurial orientation and business performance, providing evidence on a topic which has received little attention to date. The results posit that in an uncertain, dynamic environment a higher level of risk and entrepreneurial orientation benefit business performance especially when coupled with strong business and social networks.

Opportunities for Quantitative Translational Modeling in Oncology.

A 2-day meeting was held by members of the UK Quantitative Systems Pharmacology Network () in November 2018 on the topic of Translational Challenges in Oncology. Participants from a wide range of backgrounds were invited to discuss current and emerging modeling applications in nonclinical and clinical drug development, and to identify areas for improvement. This resulting perspective explores opportunities for impactful quantitative pharmacology approaches. Four key themes arose from the presentations and discussions that were held, leading to the following recommendations: Evaluate the predictivity and reproducibility of animal cancer models through precompetitive collaboration. Apply mechanism of action (MoA) based mechanistic models derived from nonclinical data to clinical trial data. Apply MoA reflective models across trial data sets to more robustly quantify the natural history of disease and response to differing interventions. Quantify more robustly the dose and concentration dependence of adverse events through mathematical modelling techniques and modified trial design.

Cerebrovascular amyloid Angiopathy in bioengineered vessels is reduced by high-density lipoprotein particles enriched in Apolipoprotein E.

BACKGROUND: Several lines of evidence suggest that high-density lipoprotein (HDL) reduces Alzheimer's disease (AD) risk by decreasing vascular beta-amyloid (Aß) deposition and inflammation, however, the mechanisms by which HDL improve cerebrovascular functions relevant to AD remain poorly understood. METHODS: Here we use a human bioengineered model of cerebral amyloid angiopathy (CAA) to define several mechanisms by which HDL reduces Aß deposition within the vasculature and attenuates endothelial inflammation as measured by monocyte binding. RESULTS: We demonstrate that HDL reduces vascular Aß accumulation independently of its principal binding protein, scavenger receptor (SR)-BI, in contrast to the SR-BI-dependent mechanism by which HDL prevents Aß-induced vascular inflammation. We describe multiple novel mechanisms by which HDL acts to reduce CAA, namely: i) altering Aß binding to collagen-I, ii) forming a complex with Aß that maintains its solubility, iii) lowering collagen-I protein levels produced by smooth-muscle cells (SMC), and iv) attenuating Aß uptake into SMC that associates with reduced low density lipoprotein related protein 1 (LRP1) levels. Furthermore, we show that HDL particles enriched in apolipoprotein (apo)E appear to be the major drivers of these effects, providing new insights into the peripheral role of apoE in AD, in particular, the fraction of HDL that contains apoE. CONCLUSION: The findings in this study identify new mechanisms by which circulating HDL, particularly HDL particles enriched in apoE, may provide vascular resilience to Aß and shed new light on a potential role of peripherally-acting apoE in AD.

The ATLANTIC study: Anti-Xa level assessment in trauma intensive care.

OBJECTIVE: To quantify the pharmacodynamic (PD) activity of daily subcutaneous (SC) enoxaparin as venous thromboembolism (VTE) prophylaxis in high-risk trauma patients admitted to the intensive care unit (ICU). METHODS: This was a prospective observational PD study conducted in the ICU of a state-wide major trauma referral centre. The study cohort included adult patients admitted to the ICU with a high risk of VTE, as defined by at least one of the following: age > 40 years, prior VTE, spinal cord injury (SCI), traumatic brain injury (TBI), major venous injury, pelvic fractures, spinal fractures requiring treatment, severe lower limb injuries, and major surgery >2 h in duration. Standard prophylactic enoxaparin dosing was 40 mg SC daily, unless amended by the treating clinician. Plasma anti-Xa activity was measured approximately 60 min before dosing (trough activity), and at 3-5 h after dosing (peak activity). Target peak and trough activity were defined as >0.2 IU/mL and >0.1 IU/mL respectively. Clinical data including the development of VTE and haemorrhagic complications were collected. RESULTS: Twenty-five patients were enrolled. Median [IQR] age, weight, and plasma creatinine were 59 years [36,70], 85 kg [76.5,93.5] and 70µmol/L [60.5,109] respectively. Median APACHE III and Injury Severity Score were 54 [42.5,66.5] and 27 [17,34] respectively. Thirteen patients suffered a TBI, in 12 cases surgery extended beyond two hours, and five patients had spinal fractures requiring treatment. Twenty-two patients received enoxaparin 40 mg SC daily, two 60 mg, and one 20 mg. Median peak and trough anti-Xa activity was 0.21 IU/mL [0.125,0.25] and 0.01 IU/mL [0,0.05] respectively. Twelve (12/25; 48%) patients had low peak activity ≤0.2 IU/mL. Twenty-one (21/23; 91%) patients had low trough activity (≤0.1 IU/mL) and in six (6/23; 26%) cases, these were undetectable. Eight (8/25; 32%) patients had documented VTE of whom seven had low trough activity. There were no major haemorrhagic complications. CONCLUSIONS: In a cohort of high risk critically ill trauma patients receiving daily SC enoxaparin as VTE chemoprophylaxis, measured peak and trough plasma anti-Xa activity was inadequate in a significant proportion. On this basis, further systematic investigation concerning dose optimisation in this patient population appears warranted.

The effects of behavioural counselling on the determinants of health behaviour change in adults with chronic musculoskeletal conditions making lifestyle changes: A systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis of controlled trials was carried out to examine the effect of behavioural counselling on determinants of behaviour change in adults with chronic, painful musculoskeletal conditions. METHODS: Seven databases were searched up to January 2019. Two reviewers independently screened title/abstracts and full texts. Eligible trials included those including participants over 18 years of age with a chronic, painful musculoskeletal condition, a measurement of at least one behavioural determinant and lifestyle behaviour, and where behavioural counselling was the distinguishing intervention. Two reviewers independently extracted data and assessed for risk of bias using the Cochrane Risk of Bias Tool. Meta-analyses were conducted, using standardized mean differences and 95% confidence intervals (CIs) when at least two trials examined the same outcome. The quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development and Evaluation approach. RESULTS: Fourteen unique trials, reported in 16 publications, were included. Low-quality evidence showed that behavioural counselling has a small effect on increasing self-reported physical activity (standardized mean difference 0.26; 95% CI 0.00, 0.53). Very-low-quality evidence showed that behavioural counselling has a moderate effect on self-efficacy related to physical activity (standardized mean difference 0.69; 95% CI 0.19, 1.18). Low-quality evidence suggested that behavioural counselling has no effect on symptoms of depression and anxiety. CONCLUSIONS: Behavioural counselling may help to increase self-reported physical activity levels in adults with chronic painful musculoskeletal conditions. Self-efficacy may be a behavioural determinant in an underlying causal pathway explaining positive lifestyle change.