Two Cases of Platypnoea-Orthodexia

Platypnoea-orthodexia syndrome is a rare cause of dyspnoea when hypoxaemia is induced by the upright position and relieved by recumbency. We report two cases in which platypnoea-orthodexia syndrome was present and caused by two different mechanisms: intracardiac shunt and intrapulmonary shunt

Identifying a core outcome set for cardiac arrest effectiveness trials

Cardiac arrest research seeks to improve survival rates and the quality of patient survival, but the comparability of research is limited by heterogeneous outcome reporting. The Core Outcome Set for Cardiac Arrest effectiveness trials (COSCA) study sought to identify the most important outcome domains that should be reported as minimum across all cardiac arrest effectiveness trials as part of a core outcome set (COS). Multiple perspectives were sought across COS development to ensure relevance. Potential outcome domains for COS inclusion were identified in: a systematic review of outcomes reported in published randomised controlled trials (RCTs) and interviews with survivors of cardiac arrest and their partners to understand the health outcomes that really matter. Consensus on the most important outcome domains was achieved in: an international modified Delphi survey and an international consensus meeting. Great heterogeneity (164 outcomes) was reported across current RCTs, failing to capture a number of outcomes important to cardiac arrest survivors identified in interviews. Across 2 rounds of ranking and rating exercise 48 outcome domains (18 health domains across 5 time points) were scored on their importance in the modified Delphi survey. Subsequently, 30 outcome domains were further discussed at a face to face consensus meeting. Three core outcome domains were defined: survival to hospital discharge/30 days, neurological outcome at hospital discharge/30 days and health related quality of life (HRQoL) within 1 year. Preliminary guidance on appropriate assessment tools were made but further evidence and understanding of the most appropriate measurement tools is required. Implementation of the defined COS has the potential to improve outcome reporting across cardiac arrest effectiveness trials, aiding the comparison of findings through homogeneous outcome reporting and ensuring the most important outcome domains to key stakeholders are reported

Disrupted sleep and associated factors in Australian dementia caregivers: a cross-sectional study

BACKGROUND: Sleep disturbance is an issue reported by caregivers. Waking at night is a feature of dementia and by proxy, sleep disturbance among caregivers is reported to be high. Little is known about the characteristics of dementia caregivers\u27 sleep and the factors that may influence sleep disruption. The purpose of this study was to investigate the sleep characteristics and disturbances of Australian caregivers of a person living with dementia. In addition, it evaluated the psychological wellbeing of caregivers by evaluating associations between mood and sleep in this population. METHODS: This study used a cross-sectional, descriptive, correlation design. Participants were recruited with the assistance of Alzheimer\u27s Australia, Dementia Australia and targeted social media advertising. In total, 104 adult, primary, informal caregivers of people with dementia participated, completing a questionnaire on demographic characteristics, the Depression, Anxiety and Stress Scale (DASS-21) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: In this study, 76% of caregivers were female who had been caring for someone living with dementia on average for 4.8 years. 44% of participants had two or more co-morbidities namely cardiovascular disease, osteoarthritis and diabetes. 94% of participants were poor sleepers with 84% with difficulty initiating sleep and 72% reporting having difficulty maintaining sleep. Overall, psychological distress was common with high levels of moderate to severe depression, anxiety and stress. Global PSQI scores were significantly positively associated with depression and anxiety, with the strongest correlation seen with stress scores. Depression scores were also moderately associated with daytime dysfunction. Stress was identified as a significant predictor of overall sleep quality. CONCLUSIONS: Sleep problems are common within the population of dementia caregivers. Due to the nature and duration of caregiving and the progression of dementia of the care recipient, there is the potential for a decline in the caregivers\u27 mental and physical health. Caregivers of those living with dementia are more likely to have comorbidities, depression, anxiety and stress. Sleep quality is correlated with emotional distress in dementia caregivers although the direction of this association is unclear. Therefore, sleep and psychological wellbeing may be intertwined, with improvements in one aspect resulting in a positive impact in the other

A survey of stress, burnout and well-being in UK dentists

Introduction It is well established that dentistry is a stressful profession, primarily due to the nature and working conditions in the dental surgery. With dramatic changes taking place in the profession in recent years it is important to establish the impact this has on dentists' well-being. Aims To determine the levels of stress and burnout in UK dentists and how this relates to well-being and identify the sources of work-related stress dentists report in different fields of practice. Materials and method An online survey comprising of validated measures examining stress, burnout and well-being in dentists was administered to British Dental Association (BDA) members and non-members. Results Valid responses were received from 2053 respondents. Dentists working in the UK exhibit high levels of stress and burnout and low well-being. General dental practitioners (GDPs) seem to be particularly affected. Issues relating to regulation and fear of litigation were deemed to be the most stressful aspects of being a dentist. Conclusions The findings from this study build upon existing research showing that dentistry is a stressful profession. The sources of this stress appear to have shifted over the years, highlighting the changing landscape of dentistry. Interventions should focus on addressing these stressors by making changes to the working conditions of dentists

Producing Glucose 6-Phosphate from Cellulosic Biomass Structural Insights into Levoglucosan Bioconversion

The most abundant carbohydrate product of cellulosic biomass pyrolysis is the anhydrosugar levoglucosan (1,6-anhydro-β-D-glucopyranose), which can be converted to glucose 6-phosphate by levoglucosan kinase (LGK). In addition to the canonical kinase phosphotransfer reaction, the conversion requires cleavage of the 1,6-anhydro ring to allow ATP-dependent phosphorylation of the sugar O6 atom. Using x-ray crystallography, we show that LGK binds two magnesium ions in the active site that are additionally coordinated with the nucleotide and water molecules to result in ideal octahedral coordination. To further verify the metal binding sites, we co-crystallized LGK in the presence of manganese instead of magnesium and solved the structure de novo using the anomalous signal from four manganese atoms in the dimeric structure. The first metal is required for catalysis, whereas our work suggests that the second is either required or significantly promotes the catalytic rate. Although the enzyme binds its sugar substrate in a similar orientation to the structurally related 1,6-anhydro-N-acetylmuramic acid kinase (AnmK), it forms markedly fewer bonding interactions with the substrate. In this orientation, the sugar is in an optimal position to couple phosphorylation with ring cleavage. We also observed a second alternate binding orientation for levoglucosan, and in these structures, ADP was found to bind with lower affinity. These combined observations provide an explanation for the high Km of LGK for levoglucosan. Greater knowledge of the factors that contribute to the catalytic efficiency of LGK can be used to improve applications of this enzyme for levoglucosan-derived biofuel production

Evaluation of a remote symptom assessment and management (SAM) system for people receiving adjuvant chemotherapy for breast or colorectal cancer: Mixed methods study

©Lisa Whitehead, Laura Emery, Deborah Kirk, Diane Twigg, Deborah Brown, Joanna Dewar. Background: The Symptom Assessment and Management (SAM) program is a structured, online, nurse-supported intervention to support symptom self-management in people receiving adjuvant chemotherapy post surgery for breast or colorectal cancer. Objective: The objective of this study was to describe the development, implementation strategy, and evaluation of the SAM system. Methods: The development of the SAM program involved 3 phases. In phase 1, the web app was developed through consultation with consumers and clinicians and of the literature to ensure that the system was evidence-based and reflected the realities of receiving treatment and supporting patients through treatment. In phase 2, 7 participants recorded the severity of 6 symptoms daily over the course of 1 cycle of chemotherapy. In phase 3, 17 participants recorded their symptoms daily over the course of 3 cycles of chemotherapy. Once symptoms were recorded, participants received immediate feedback on the severity of their symptoms and self-management recommendations, which could include seeking immediate medical attention. Data on quality of life, symptom burden, anxiety and depression, distress, and self-efficacy were collected during treatment; participants’ perceptions of the SAM program were evaluated following participation via interview. Results: The outcomes of the SAM project include the development of a system that is reliable and easy to use and navigate. Participants reported benefits related to using the SAM program that included feeling more in control of managing their symptoms and feeling reassured. Engagement with the system on a daily basis was variable, with some participants completing the symptom tracker daily and others engaging some of the time. The feedback from all participants was that the system was easy to navigate and the information was relevant and supportive. Conclusions: The SAM program has the potential to enhance the management of symptoms for people receiving chemotherapy treatment. The system creates an accurate repository of symptoms that can be accessed easily and highlight patterns in symptom experience. These can be shared with clinicians, with patient permission, to inform and support treatment plans. The potential to predict the risk of developing severe symptoms can be developed to anticipate the need for care and support. Further considerations on how to increase engagement with the system, the value of the system for people diagnosed with other tumor types and treatment regimes, and the incorporation of the system into everyday clinical practice are needed

Parallel evolutionary pathways to antibiotic resistance selected by biocide exposure

OBJECTIVES: Biocides are widely used to prevent infection. We aimed to determine whether exposure of Salmonella to various biocides could act as a driver of antibiotic resistance. METHODS: Salmonella enterica serovar Typhimurium was exposed to four biocides with differing modes of action. Antibiotic-resistant mutants were selected during exposure to all biocides and characterized phenotypically and genotypically to identify mechanisms of resistance. RESULTS: All biocides tested selected MDR mutants with decreased antibiotic susceptibility; these occurred randomly throughout the experiments. Mutations that resulted in de-repression of the multidrug efflux pump AcrAB-TolC were seen in MDR mutants. A novel mutation in rpoA was also selected and contributed to the MDR phenotype. Other mutants were highly resistant to both quinolone antibiotics and the biocide triclosan. CONCLUSIONS: This study shows that exposure of bacteria to biocides can select for antibiotic-resistant mutants and this is mediated by clinically relevant mechanisms of resistance prevalent in human pathogens

Biopsychosocial Intervention for Stroke Carers (BISC): protocol for a feasibility randomized controlled trial

Introduction Reducing length of hospital stay for stroke survivors often creates a shift in the responsibility of care towards informal carers. Adjustment to the caregiving process is experienced by many carers as overwhelming, complex and demanding, and can have a detrimental impact on mental and physical health and wellbeing. National policy guidelines recommend that carers’ needs are considered and addressed; despite this, few interventions have been developed and empirically evaluated. We developed a biopsychosocial intervention in collaboration with carers of stroke survivors. Our aim is to determine whether the intervention can be delivered in a group setting and evaluated using a randomised controlled trial (RCT). Methods and Analysis Feasibility randomised controlled trial (RCT) and nested qualitative interview study. We aim to recruit up to 40 stroke carers within one year of the stroke onset. Carers are randomised to usual care or usual care plus biopsychosocial intervention. Each intervention group will consist of five stroke carers. The intervention will focus on: psychoeducation, psychological adjustment to stroke, strategies for reducing unwanted negative thoughts and emotions, and problem solving strategies. The main outcome is the feasibility of conducting an RCT. Carer outcomes at six months include: anxiety and depression, quality of life, and carer strain. Data is also collected from stroke survivors at baseline and six months including: level of disability, anxiety and depression, and quality of life. Ethics and Dissemination Favourable ethical opinion was provided by East Midlands – Nottingham2 Research Ethics Committee (14/EMI/1264). This study will determine whether delivery of the biopsychosocial intervention is feasible and acceptable to stroke carers within a group format. It will also determine whether it is feasible to evaluate the effects of the biopsychosocial intervention in an RCT. We will disseminate our findings through peer-reviewed publications and presentations at national and international conferences