RHABDOMYOLYSIS INDUCED BY ANAESTHESIA WITH INTRAOPERATIVE CARDIAC ARREST

A 9-year-old boy undergoing anaesthesia including suxamethonium and halothane suffered cardiac arrest on two occasions. Clinical and laboratory examination subsequently showed that the patient had suffered from acute rhabdomyolysis. The eventual recovery was satisfactor

A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease

Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included sequential 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was −10.1 nmol bone collagen equivalents/mmol creatinine (−32.8 %; P = 0.0124); median bALP change was −16.7 ng/mL (−42.0 %; P = 0.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (≥25 % reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3 % metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease

On the mechanical behaviour of PEEK and HA cranial implants under impact loading

The human head can be subjected to numerous impact loadings such as those produced by a fall or during sport activities. These accidents can result in skull fracture and in some complex cases, part of the skull may need to be replaced by a biomedical implant. Even when the skull is not damaged, such accidents can result in brain swelling treated by decompressive craniectomy. Usually, after recovery, the part of the skull that has been removed is replaced by a prosthesis. In such situations, a computational tool able to analyse the choice of prosthesis material depending on the patient's specific activity has the potential to be extremely useful for clinicians. The work proposed here focusses on the development and use of a numerical model for the analysis of cranial implants under impact conditions. In particular, two main biomaterials commonly employed for this kind of prosthesis are polyether-ether-ketone (PEEK) and macroporous hydroxyapatite (HA). In order to study the suitability of these implants, a finite element head model comprising scalp, skull, cerebral falx, cerebrospinal fluid and brain tissues, with a cranial implant replacing part of the skull has been developed from magnetic resonance imaging data. The human tissues and these two biocompatible materials have been independently studied and their constitutive models are provided here. A computational model of the human head under impact loading is then implemented and validated, and a numerical comparison of the mechanical impact response of PEEK and HA implants is presented. This comparison was carried out in terms of the effectiveness of both implants in ensuring structural integrity and preventing traumatic brain injury.The researchers of the University Carlos III are indebted to the Ministerio de Economía y Competitividad de España (Project DPI2014-57989-P) and Vicerrectorado de Política Científica UC3M (Project 2013-00219-002) for the financial support. A.J. acknowledges funding from the European Union's Seventh Framework Programme (FP7 2007–2013) ERC Grant Agreement No. 306587. MRI data were provided by the Human Connectome Project, WUMinn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. Finally, we would like to thank Dr. S Barhli and Prof. J Marrow for valuable assistance with the X-ray tomography; the machine used was bought from EPSRC Grant EP/M02833X/1 “University of Oxford: experimental equipment upgrade”. Open Access funded by European Research Counci

Effect of maternal panic disorder on mother-child interaction and relation to child anxiety and child self-efficacy

To determine whether mothers with panic disorder with or without agoraphobia interacted differently with their children than normal control mothers, 86 mothers and their adolescents (aged between 13 and 23 years) were observed during a structured play situation. Maternal as well as adolescent anxiety status was assessed according to a structured diagnostic interview. Results showed that mothers with panic disorder/agoraphobia showed more verbal control, were more criticizing and less sensitive during mother-child interaction than mothers without current mental disorders. Moreover, more conflicts were observed between mother and child dyadic interactions when the mother suffered from panic disorder. The comparison of parenting behaviors among anxious and non-anxious children did not reveal any significant differences. These findings support an association between parental over-control and rejection and maternal but not child anxiety and suggest that particularly mother anxiety status is an important determinant of parenting behavior. Finally, an association was found between children’s perceived self-efficacy, parental control and child anxiety symptoms

Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: Phase 1b study.

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.We thank the patients and families who participated in this study, caregivers, the study investigators, and their staff, and the JPCE (NCT02779751) clinical trial team. Pembrolizumab was provided by Merck & Co., Inc., Kenilworth, NJ, USA. We thank Anne Chain from the Department of Quantitative Pharmacology & PharmacometricsImmune/Oncology, Merck & Co., Inc., Kenilworth, NJ, USA for her contributions to this work, which included pembrolizumab PK and ADA analysis. This work and medical writing support was funded by Eli Lilly and Company.S

Stress among UK academics : identifying who copes best?

This paper examined the levels of stress and coping strategies among UK academics. Adopting a positive psychology approach, the influence of the character strengths of hope, optimism, gratitude and self-efficacy, on stress, subjective well-being (SWB), and mental health (GHQ) was examined in 216 academics in a UK university. The study explored the relationship between coping styles and work-coping variables of sense of coherence and work locus of control and stress. No significant differences on the stress, well-being and mental health measures were found for participants' gender, whether in full-time or part-time employment and level of seniority within the university. Participants using problem-focussed coping experienced lower levels of stress while dysfunctional coping was a positive predictor of stress. Hope agency, hope pathway, gratitude, optimism and self-efficacy were the strongest positive predictors of satisfaction with life (SWL), while levels of perceived stress negatively predicted SWL. Gratitude, hope agency and self-efficacy positively predicted positive affect, while stress was a negative predictor. Gratitude, hope agency, self-efficacy and optimism were negative significant predictors of negative affect while stress was a positive predictor. Gratitude positively predicted mental health, while stress was a negative predictor and optimism was a significant moderator of the relationship between stress and mental health. Academics with higher levels of gratitude, self-efficacy, hope and optimism report lower levels of stress at work and higher levels of well-being as measured by higher life satisfaction, higher positive affect and lower negative affect. New approaches to stress management training are suggested based on these findings

Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial.

BACKGROUND Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. PATIENTS AND METHODS Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. RESULTS The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). CONCLUSIONS Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors