In the Rat Hippocampus, Pilocarpine-Induced Status Epilepticus Is Associated with Reactive Glia and Concomitant Increased Expression of CD31, PDGFRß, and Collagen IV in Endothelial Cells and Pericytes of the Blood-Brain Barrier.

In humans and animal models, temporal lobe epilepsy (TLE) is associated with reorganization of hippocampal neuronal networks, gliosis, neuroinflammation, and loss of integrity of the blood-brain barrier (BBB). More than 30% of epilepsies remain intractable, and characterization of the molecular mechanisms involved in BBB dysfunction is essential to the identification of new therapeutic strategies. In this work, we induced status epilepticus in rats through injection of the proconvulsant drug pilocarpine, which leads to TLE. Using RT-qPCR, double immunohistochemistry, and confocal imaging, we studied the regulation of reactive glia and vascular markers at different time points of epileptogenesis (latent phase-3, 7, and 14 days; chronic phase-1 and 3 months). In the hippocampus, increased expression of mRNA encoding the glial proteins GFAP and Iba1 confirmed neuroinflammatory status. We report for the first time the concomitant induction of the specific proteins CD31, PDGFRß, and ColIV-which peak at the same time points as inflammation-in the endothelial cells, pericytes, and basement membrane of the BBB. The altered expression of these proteins occurs early in TLE, during the latent phase, suggesting that they could be associated with the early rupture and pathogenicity of the BBB that will contribute to the chronic phase of epilepsy.

Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story.

BACKGROUND: A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections. METHODS: HPeV3-positive samples collected from hospitalized infants aged 5-252 days in 2 Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples. RESULTS: Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019-2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants. CONCLUSIONS: HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence.

Longitudinal change in sleep, functional, and behavioural characteristics in a cohort of children with Down syndrome.

This paper describes the longitudinal change in sleep, functional, and behavioural characteristics in a cohort of children with Down syndrome, including the effect of sleep interventions in a subset. A prospective longitudinal cohort study was undertaken in children with Down syndrome aged 3-16 years comparing (1) children referred to a tertiary sleep medicine clinic who received sleep hygiene advice and an additional sleep treatment (DSref_I) with (2) children attending the same clinic who only received sleep hygiene advice (DSref_N) and (3) children recruited from the community who, were not receiving any treatment (DScomm). Data collected included demographic and medical history information, Child Sleep Habits Questionnaire-Abbreviated (CSHQ-A), Life-Habits Questionnaire (Life-H) and Child Behaviour Checklist (CBCL) at baseline and then 6-monthly for a total of 18 months. Any sleep interventions during this time were recorded. A total of 57 children were included (DSref_I, n = 16; DSref_N, n = 25; DScomm, n = 16). At recruitment, the median CSHQ-A total score was high (>41) in all three subgroups, but highest in the DSref_I subgroup (median [interquartile range] Dsref_I score 58 [53-66] versus DSref_N score 49 [43-53], p = 0.019). Although improved, 80% of participants in the DSref_I subgroup still had a CSHQ-A total score >41 at the last assessment point. The median total Life-H and total CBCL scores were not significantly different between groups at baseline and there was no significant time, group, or interaction effect seen through the study. Over an 18-month period, sleep problems were seen to persist in children with Down syndrome. Treatment resulted in only modest improvements in sleep.

The impact of an autonomous nurse-led high-flow nasal cannula oxygen protocol on clinical outcomes of infants with bronchiolitis.

OBJECTIVE: To investigate the relationship of the implementation of a nurse-led high-flow nasal cannula oxygen protocol on the clinical outcomes of infants with bronchiolitis in a regional paediatric unit. BACKGROUND: Bronchiolitis is a common lower respiratory illness and is the leading cause for hospitalisation of infants globally. Standard care involves the provision of supportive measures. Historically, supplemental oxygen was provided by low-flow nasal cannula. High-flow nasal cannula oxygen has been increasingly adopted despite limited evidence of its efficacy. METHODS: This study employed non-equivalent, post-implementation only design to explore clinical outcomes of infants with bronchiolitis admitted for high-flow nasal cannula oxygen therapy. The study compared infants in the 24 months before and after the initiation of a high-flow nasal cannula protocol. The primary clinical outcome was length of stay, secondary outcomes included time on high flow, weaning time, escalation of care and time outside of physiological parameters. Implementation strategy evaluation was measured by compliance with applying the protocol, reported as episodes of variance, and duration of variance. The StaRI checklist was selected as the most appropriate reporting guideline. RESULTS: A total of 80 patients were admitted with bronchiolitis and received high-flow nasal cannula oxygen therapy during a 48-month period; 37 patients were prior, and 43 after, the introduction of a nurse-led high-flow nasal cannula protocol. Length of stay was significantly reduced in the post-implementation group compared to the historical control group (83.8 vs. 61.3 h). Time on high flow and weaning time was decreased in the post-implementation group compared to the control group (33.5 vs. 26.7 h and 26 vs.12.25 h, respectively); however, these did not reach statistical significance. There was varied application of the HFNC protocol. CONCLUSIONS: The implementation of a nurse-led high-flow nasal cannula protocol was associated with a reduced length of stay. RELEVANCE TO CLINICAL PRACTICE: This study demonstrated that infants with bronchiolitis that were treated with a nurse-led high-flow nasal cannula (HFNC) therapy protocol had positive effects on clinical outcomes including a shorter length of stay than compared with those with physician-directed care in a regional paediatric unit. A weight-based (2 L/kg) HFNC therapy was safely administered to infants with bronchiolitis in a regional hospital paediatric ward with no paediatric intensive care unit (PICU).

Healthier Together: Implementation and evaluation of a co-designed, culturally tailored childhood obesity community prevention program for Maori and Pacific Islander children and families.

ISSUE ADDRESSED: Co-designed and culturally tailored preventive initiatives delivered in childhood have high potential to close the cross-cultural gap in health outcomes of priority populations. Maori and Pacific Islander people living in Australia exhibit a higher prevalence of overweight and obesity and higher rates of multimorbidity, including heart disease, cancer and diabetes. METHODS: This mixed-methods, pilot implementation and evaluation study, aimed to evaluate the implementation of a community-based, co-designed and culturally tailored childhood obesity prevention program, using quantitative (pre-post anthropometric measurement, pre-post health behaviour questionnaire) and qualitative (semi-structured interview) methods. Sessions relating to healthy eating, physical activity and positive parenting practices were delivered to families residing in Brisbane (Australia) over 8-weeks. RESULTS: Data were collected from a total of 66 children (mean age 11, SD 4) and 38 parents (mean age 40, SD 8) of Maori and Pacific Islander background, from July 2018 to November 2019. Anthropometric changes included a reduction in Body Mass Index (BMI) z-score among 59% of children (median change -0.02, n = 38, p = 0.17) and BMI among 47% of adults (median change +0.06 kg/m2 , n = 18, p = 0.64). Significant improvements (p < 0.05) in self-reported health behaviours from pre- to post-program included increased vegetable consumption among children, decreased discretionary food intake of children, decreased discretionary drink consumption among both children and adults, increased minutes of daily physical activity among adults and increased parental confidence in the healthy diets of their children. Qualitative data revealed participants valued the inclusion of all family members, learning of practical skills and cultural tailoring delivered by the Multicultural Health Coaches. CONCLUSIONS: This study provides preliminary evidence that the Healthier Together program improved self-reported health behaviours and physical activity levels among Maori and Pacific Islander children and their families in the short-term; however, due to the small sample size, these results must be interpreted carefully. The program empowered change via cultural tailoring and accessibility; however, long-term implementation and evaluation with a larger cohort is needed to validate the observed health behaviour improvements and their sustainability. SO WHAT?: The co-design framework that informed program development and key learnings of implementation will provide guidance to health practitioners, health workers, public health professionals and policy makers to develop inclusive and pragmatic co-design solutions for priority cultural populations in Australia. Health outcomes will improve as a result, promoting health equity for future generations.

Ischemic Stroke in Patients With Hypertrophic Cardiomyopathy According to Presence or Absence of Atrial Fibrillation.

BACKGROUND AND PURPOSE: Patients with hypertrophic cardiomyopathy (HCM) have high risk of ischemic stroke (IS), especially if atrial fibrillation (AF) is present. Improvements in risk stratification are needed to help identify those patients with HCM at higher risk of stroke, whether AF is present or not. METHODS: This French longitudinal cohort study from the database covering hospital care from 2010 to 2019 analyzed adults hospitalized with isolated HCM. A logistic regression model was used to construct a French HCM score, which was compared with the HCM Risk-CVA and CHA2DS2-VASc scores using c-indexes and calibration analysis. RESULTS: In 32 206 patients with isolated HCM, 12 498 (38.8%) had AF, and 2489 (7.7%) sustained an IS during follow-up. AF in patients with HCM was independently associated with a higher risk for death (hazard ratio, 1.129 [95% CI, 1.088-1.172]), cardiovascular death (hazard ratio, 1.254 [95% CI, 1.177-1.337]), IS (hazard ratio, 1.210 [95% CI, 1.111-1.317]), and other major cardiovascular events. Independent predictors of IS in HCM were older age, heart failure, AF, prior IS, smoking and poor nutrition (all P<0.05). For the HCM Risk-CVA score, CHA2DS2-VASc score and a French HCM score, all c-indexes were 0.65 to 0.70, with good calibration. Among patients with AF, the CHA2DS2-VASc score had marginal improvement over the HCM Risk-CVA score but was less predictive compared with the French HCM score (P=0.001). In patients without AF, both HCM Risk-CVA score and the French HCM score had significantly better prediction compared with CHA2DS2-VASc (both P<0.0001). Decision curve analysis demonstrated that the French HCM score had the best clinical usefulness of the 3 tested risk scores. CONCLUSIONS: Patients with HCM have a high prevalence of AF and a significant risk of IS, and the presence of AF in patients with HCM was independently associated with worse outcomes. A simple French HCM score shows good prediction of IS in patients with HCM and clinical usefulness, with good calibration.

MT5-MMP controls APP and ß-CTF/C99 metabolism through proteolytic-dependent and -independent mechanisms relevant for Alzheimer's disease.

We previously discovered the implication of membrane-type 5-matrix metalloproteinase (MT5-MMP) in Alzheimer's disease (AD) pathogenesis. Here, we shed new light on pathogenic mechanisms by which MT5-MMP controls the processing of amyloid precursor protein (APP) and the fate of amyloid beta peptide (Aß) as well as its precursor C99, and C83. We found in human embryonic kidney cells (HEK) carrying the APP Swedish familial mutation (HEKswe) that deleting the C-terminal non-catalytic domains of MT5-MMP hampered its ability to process APP and release the soluble 95 kDa form (sAPP95). Catalytically inactive MT5-MMP variants increased the levels of Aß and promoted APP/C99 sorting in the endolysosomal system, likely through interactions of the proteinase C-terminal portion with C99. Most interestingly, the deletion of the C-terminal domain of MT5-MMP caused a strong degradation of C99 by the proteasome and prevented Aß accumulation. These discoveries reveal new control of MT5-MMP over APP by proteolytic and non-proteolytic mechanisms driven by the C-terminal domains of the proteinase. The targeting of these non-catalytic domains of MT5-MMP could, therefore, provide new insights into the therapeutic regulation of APP-related pathology in AD.

Neurotensin receptor 2 is induced in astrocytes and brain endothelial cells in relation to neuroinflammation following pilocarpine-induced seizures in rats.

Neurotensin (NT) acts as a primary neurotransmitter and neuromodulator in the CNS and has been involved in a number of CNS pathologies including epilepsy. NT mediates its central and peripheral effects by interacting with the NTSR1, NTSR2, and Sort1/NTSR3 receptor subtypes. To date, little is known about the precise expression of the NT receptors in brain neural cells and their regulation in pathology. In the present work, we studied the cellular distribution of the NTSR2 protein in the rat hippocampus and questioned whether its expression was modulated in conditions of neuroinflammation using a model of temporal lobe epilepsy induced by pilocarpine. This model is characterized by a rapid and intense inflammatory reaction with reactive gliosis in the hippocampus. We show that NTSR2 protein is expressed in hippocampal astrocytes and its expression increases together with astrocyte reactivity following induction of status epilepticus. NTSR2 immunoreactivity is also increased in astrocytes proximal to blood vessels and their end-feet, and in endothelial cells. Proinflammatory factors such as IL1ß and LPS induced NTSR2 mRNA and protein in cultured astroglial cells. Antagonizing NTSR2 with SR142948A decreased NTSR2 expression as well as astroglial reactivity. Together, our results suggest that NTSR2 is implicated in astroglial and gliovascular inflammation and that targeting the NTSR2 receptor may open new avenues in the regulation of neuroinflammation in CNS diseases.

Oxygen supplementation during exercise improves leg muscle fatigue in chronic fibrotic interstitial lung disease.

BACKGROUND: Exercise-induced hypoxaemia is a hallmark of chronic fibrotic interstitial lung disease (f-ILD). It remains unclear whether patients' severe hypoxaemia may exaggerate locomotor muscle fatigue and, if so, to what extent oxygen (O2) supplementation can ameliorate these abnormalities. METHODS: Fifteen patients (12 males, 9 with idiopathic pulmonary fibrosis) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) while breathing medical air. Fifteen age-matched and sex-matched controls cycled up to patients' Tlim. Patients repeated the exercise test on supplemental O2 (42%±7%) for the same duration. Near-infrared spectroscopy assessed vastus lateralis oxyhaemoglobin concentration ((HbO2)). Pre-exercise to postexercise variation in twitch force (∆Tw) induced by femoral nerve magnetic stimulation quantified muscle fatigue. RESULTS: Patients showed severe hypoxaemia (lowest O2 saturation by pulse oximetry=80.0%±7.6%) which was associated with a blunted increase in muscle (HbO2) during exercise vs controls (+1.3±0.3 µmol vs +4.4±0.4 µmol, respectively; p<0.001). Despite exercising at work rates ∼ one-third lower than controls (42±13 W vs 66±13 W), ∆Tw was greater in patients (∆Tw/external work performed by the leg muscles=-0.59±0.21 %/kJ vs -0.25±0.19 %/kJ; p<0.001). Reversal of exertional hypoxaemia with supplemental O2 was associated with a significant increase in muscle (HbO2), leading to a reduced decrease in ∆Tw in patients (-0.33±0.19 %/kJ; p<0.001 vs air). Supplemental O2 significantly improved leg discomfort (p=0.005). CONCLUSION: O2 supplementation during exercise improves leg muscle oxygenation and fatigue in f-ILD. Lessening peripheral muscle fatigue to enhance exercise tolerance is a neglected therapeutic target that deserves clinical attention in this patient population.

The IC-D score for predicting prophylactic cardioverter-defibrillator implantation following acute myocardial infarction.

BACKGROUND: A reduced left ventricular ejection fraction (LVEF) ≤35% ≥6 weeks following an acute myocardial infarction (MI) may indicate prophylactic implantation of a cardioverter-defibrillator (ICD). We sought to find predictors of absence of significant left ventricular (LV) remodeling post-MI. METHODS: All consecutive patients hospitalized for acute MI with an LVEF ≤35% at discharge in our institution from 2010 were retrospectively included. Patients were assigned to two groups according to the persistence of an LVEF ≤35% (ICD+) or a recovery >35% (ICD-). Logistic regression was performed to build a predictive score, which was then externally validated. RESULTS: Among a total of 1533 consecutive MI patients, 150 met inclusion criteria, 53 (35%) in the ICD+ group and 97 in the ICD group. After multivariable analyses, an LVEF ≤25% at discharge (adjusted OR 6.23 [2.47 to 17.0], p < .0001) and a CPK peak at the MI acute phase >4600 UI/L (adjusted OR 9.99 [4.27 to 25.3], p < .0001) both independently predicted non-recovery at 6 weeks. The IC-D (Increased Cpk-LV Dysfunction) score predicted persistent LVEF ≤35% with areas under curve of 0.83 and 0.73, in the study population and in a multicenter validation cohort of 150 patients, respectively (p < .0001). CONCLUSIONS: The association of a severely reduced LVEF and a major release of myocardial necrosis biomarkers at the acute phase of MI predict unfavorable remodeling, and prophylactic ICD implantation.

Cognitive parameters in children with mild obstructive sleep disordered breathing.

PURPOSE: Sleep disordered breathing (SDB) in children is commonly described as a continuum from primary snoring (PS) to obstructive sleep apnea (OSA), based on apnea indices from polysomnography (PSG). This study evaluated the difference in neurocognitive and behavioral parameters, prior to treatment, in symptomatic pre-school children with PSG-diagnosed OSA and PS. METHODS: All children had positive Pediatric Sleep Questionnaire (PSQ) results and were deemed suitable for adenotonsillectomy by an ENT surgeon. Neurocognitive and behavioral data were analyzed in pre-school children at recruitment for the POSTA study (The Pre-School OSA Tonsillectomy Adenoidectomy Study). Data were compared between PS and OSA groups, with Obstructive Apnea-Hypopnea Index, OAHI < 1/h or 1-10/h, respectively. RESULTS: Ninety-one children were enrolled, including 52 with OSA and 39 with PS. Distribution of IQ (using Brief Intellectual Ability, BIA) was slightly skewed towards higher values compared with the reference population. No significant differences were found in neurocognitive or behavioral parameters for children with OSA versus those with PS. DISCUSSION: Neurocognitive and behavioral parameters were similar in pre-school children symptomatic for OSA, regardless of whether or not PSG diagnosed PS or OSA. Despite having identical symptoms, children with PS on PSG are often treated conservatively, whereas those with OSA on PSG are considered for adenotonsillectomy. This study demonstrates that, regardless of whether or not PS or OSA is diagnosed on PSG, symptoms, neurocognition, and behavior are identical in these groups. We conclude that symptoms and behavioral disturbances should be considered in addition to OAHI when determining the need for treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials registration number ACTRN12611000021976.

Developing interprofessional collaboration between clinicians, interpreters, and translators in healthcare settings: outcomes from face-to-face training.

Interprofessional collaboration between clinicians, interpreters, and translators is crucial to providing care for consumers with limited English proficiency. Interprofessional training for these professions has been overlooked outside of the medical field. This study investigated whether face-to-face training for speech pathologists, interpreters, and translators improved their knowledge, confidence, practice, and attitudes to engage in interprofessional collaboration. It also examined whether single-profession training for speech pathologists can produce similar training outcomes when delivered to multiple healthcare professions. Thirty interpreters and translators (30 training), 49 speech pathologists (27 training, 22 control), and a mixed group of 24 clinicians from eight professions (16 training, 8 control) completed surveys before, after, and two months after their respective training event. Training outcomes were similar across cohorts. Knowledge and confidence improved and were maintained after two months. Attitudes toward interprofessional collaboration were positive despite perceptions of challenge, and this was largely unchanged after training. Intent to implement optimal practices after training was greater than self-reported practices two months later. While years of professional experience did not affect training outcomes for clinicians, knowledge improvement for interpreters was associated with having less professional experience. Findings highlight the need to reevaluate service planning, policy, and workforce development strategies alongside foundation level training to deliver effective interprofessional education for clinicians, interpreters, and translators in healthcare settings.

Clinically Significant Fibrosis Is Associated With Longitudinal Increases in Fibrosis-4 and Nonalcoholic Fatty Liver Disease Fibrosis Scores.

BACKGROUND & AIMS: There is limited knowledge regarding the longitudinal utility of biomarkers of fibrosis, such as the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) or the fibrosis-4 score (FIB-4) score. We examined longitudinal changes in the NFS and the FIB-4 score in patients with NAFLD, with and without clinically significant fibrosis (CSF). METHODS: We performed a retrospective study of 230 patients with NAFLD, collecting clinical and laboratory records to calculate NFS and FIB-4 scores at 6 monthly intervals for 5 years before hepatology assessment of fibrosis. Linear mixed models with random intercept and slope and adjusted for age at baseline were used to assess the progression of NFS and log-transformed FIB-4 scores over time in subjects with and without CSF, determined by liver stiffness measurements of 8.2 kPa or greater. RESULTS: Patients had a median of 11 (minimum, 10; maximum, 11) retrospective observations over a median time period of 5 years (minimum, 4.5 y; maximum, 5 y). Of patients with low baseline NFS and FIB-4 scores, 31.11% and 37.76%, respectively, had CSF at the time of hepatology assessment. There was a correlation between NFS and log10 FIB-4 over time (repeated measure r = 0.55; 95% CI, 0.52-0.59). The rate of increase in NFS and log10 FIB-4 was significantly higher in patients with than without CSF (both P < .001). Predicted NFS increased by 0.17 and 0.06 units per year in subjects with and without CSF, respectively. Predicted log10 FIB-4 score increased by 0.032 and 0.0003 units per year in subjects with and without CSF, respectively. CONCLUSIONS: Noninvasively measured fibrosis scores increase progressively in patients with NAFLD and CSF. Further studies are needed to determine whether repeated measurements can identify patients at risk for CSF.

Proamyloidogenic effects of membrane type 1 matrix metalloproteinase involve MMP-2 and BACE-1 activities, and the modulation of APP trafficking.

We previously demonstrated that membrane type 1 (MT1) matrix metalloproteinase (MMP) was up-regulated in the hippocampus of the model of transgenic mice bearing 5 familial mutations on human amyloid precursor protein (APP) and presenilin 1 of Alzheimer disease (AD), and that the proteinase increased the levels of amyloid ß peptide (Aß) and its APP C-terminal fragment of 99 aa in a heterologous cell system. Here we provide further evidence that MT1-MMP interacts with APP and promotes amyloidogenesis in a proteolytic-dependent manner in Swedish APP-expressing human embryonic kidney 293 (HEKswe) cells. MT1-MMP-mediated processing of APP releases a soluble APP fragment, sAPP95. This process partly requires the activation of endogenous MMP-2 but is independent of ß-site APP cleaving enzyme 1 (BACE-1) or α-secretase activities. In contrast, MT1-MMP-mediated increase of Aß levels involved BACE-1 activity and was inhibited by tissue inhibitor of MMP-2, a natural inhibitor of both MT1-MMP and MMP-2. Interestingly, near abolishment of basal Aß production upon BACE-1 inhibition was rescued by MT1-MMP, indicating that the latter could mimic ß-secretase-like activity. Moreover, MT1-MMP promoted APP/Aß localization in endosomes, where Aß production mainly occurs. These data unveil new mechanistic insights to support the proamyloidogenic role of MT1-MMP based on APP processing and trafficking, and reinforce the idea that this proteinase may become a new potential therapeutic target in AD.-Paumier, J.-M., Py, N. A., González, L. G., Bernard, A., Stephan, D., Louis, L., Checler, F., Khrestchatisky, M., Baranger, K., Rivera, S. Proamyloidogenic effects of membrane type 1 matrix metalloproteinase involve MMP-2 and BACE-1 activities, and the modulation of APP trafficking.

Communicating Actively Responding Empathically (CARE): Comparison of Communication Training Workshops for Health Professionals Working in Cancer Care.

Accessing full-day communication skills training can be challenging for health professionals working in cancer care. This study aimed to examine the effectiveness of Communicating Actively, Responding Empathically (CARE Express), a modified 2-h communication skills training course, across measures of health professional confidence, skills and attitudes. Cancer care health professionals (n = 147) were recruited from allied health, nursing and medical disciplines, using a partial randomisation to allocate to three arms: control, two-hour training (CARE Express) and 1-day training (CARE). Perceived confidence and skills were measured by self-report using a purpose-built scale, and written responses to a challenging clinical encounter were obtained at baseline, post-training and three-months post-training. Attitudes toward psychosocial issues were evaluated with the Physician Belief Scale at baseline and 3 months post-training. No changes were observed in the control group (n = 50) from baseline to 3 months follow-up. Participants in the CARE Express (n = 48) and CARE (n = 49) groups had significant improvement in confidence in identifying/responding to emotions between baseline and 3 months post-training (p < 0.001), as well as their attitude toward psychosocial care (p < 0.001). A significant increase in "acknowledging" responses from baseline to 3 months was also observed for CARE Express and CARE (p < 0.001), with no difference between groups. CARE Express and CARE resulted in changes in confidence in emotional identification/response, psychosocial focus and communication skills maintained at 3 months post-training. Whilst the 1-day workshop has been regarded as gold standard, this study has revealed positive outcomes with a modified 2-h version, thus offering a potential alternate training model.

Exercise intolerance in comorbid COPD and heart failure: the role of impaired aerobic function.

Impaired aerobic function is a potential mechanism of exercise intolerance in patients with combined cardiorespiratory disease. We investigated the pathophysiological and sensory consequences of a low change in oxygen uptake (ΔV'O2 )/change in work rate (ΔWR) relationship during incremental exercise in patients with coexisting chronic obstructive pulmonary disease (COPD) and systolic heart failure (HF).After clinical stabilisation, 51 COPD-HF patients performed an incremental cardiopulmonary exercise test to symptom limitation. Cardiac output was non-invasively measured (impedance cardiography) in a subset of patients (n=18).27 patients presented with ΔV'O2 /ΔWR below the lower limit of normal. Despite similar forced expiratory volume in 1 s and ejection fraction, the low ΔV'O2 /ΔWR group showed higher end-diastolic volume, lower inspiratory capacity and lower transfer factor compared to their counterparts (p<0.05). Peak WR and peak V'O2 were ∼15% and ∼30% lower, respectively, in the former group: those findings were associated with greater symptom burden in daily life and at a given exercise intensity (leg discomfort and dyspnoea). The low ΔV'O2 /ΔWR group presented with other evidences of impaired aerobic function (sluggish V'O2 kinetics, earlier anaerobic threshold) and cardiocirculatory performance (lower oxygen pulse, lower stroke volume and cardiac output) (p<0.05). Despite similar exertional hypoxaemia, they showed worse ventilatory inefficiency and higher operating lung volumes, which led to greater mechanical inspiratory constraints (p<0.05).Impaired aerobic function due to negative cardiopulmonary-muscular interactions is an important determinant of exercise intolerance in patients with COPD-HF. Treatment strategies to improve oxygen delivery to and/or utilisation by the peripheral muscles might prove particularly beneficial to these patients.

How to upgrade a leadless pacemaker to cardiac resynchronization therapy.

INTRODUCTION: We sought to develop an efficient method to upgrade pacing-induced cardiomyopathy (PICM) patients from a leadless pacemaker (LPM) to cardiac resynchronization therapy. METHODS AND RESULTS: Three consecutive patients with chronic atrial fibrillation, implanted with an LPM, with permanent right ventricular pacing, and who developed left ventricular systolic dysfunction due to PICM, were included. A conventional biventricular pacemaker with two different coronary sinus leads, one used for left lateral ventricular pacing, one for early right ventricular sensing, was implanted. It was then synchronized with the LPM working as the right ventricular pacing lead to provide biventricular pacing. The upgrading technique was feasible in all cases, without any perioperative complication. All patients had an improved clinical status during follow-up. CONCLUSION: This new upgrading technique allows efficient cardiac resynchronization therapy in LPM patients while preventing tricuspid valve crossing and providing an increased battery longevity.

Invasive fungal infections in children with acute lymphoblastic leukaemia: Results from four Australian centres, 2003-2013.

BACKGROUND: Invasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL. METHODS: IFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria with a 'modified-possible' category included. RESULTS: A total of 123 IFI episodes in 119 patients with ALL were included. A proven, probable, possible and modified-possible IFI was diagnosed in 56 (45.5%), 22 (17.9%), 39 (31.7%) and six (4.9%) episodes, respectively. The prevalence was 9.7% (95% confidence interval [CI] 8-11.4%) overall and 23.5% (95% CI 14.5-32.5%) for relapsed/refractory ALL. For non-relapsed ALL, the IFI prevalence was significantly higher for children with high-risk compared to standard-risk ALL (14.5% vs 7.3%, P = .009), and IFI were more common during induction, consolidation and delayed intensification phases. Mould infections occurred more frequently than non-mould infections. Thirteen children (10.9%) died within 6 months of IFI diagnosis with five deaths (4.2%) attributable to an IFI. CONCLUSIONS: IFI is more common in children with high-risk ALL and in relapsed disease. Overall survival was encouraging, with IFI contributing to very few deaths.