The effect of intravenous iron on postoperative transfusion requirements in hip fracture patients: study protocol for a randomized controlled trial

Background Anaemia following hip fracture is common. Approximately 30 to 45% of patients have haemoglobin concentrations below population norms on admission, and around 10% are severely anaemic. Anaemia on admission, and in the postoperative period, is associated with poor outcomes with regard to mobility, postoperative mortality and readmission. There is currently no clear consensus on the optimal method of managing perioperative anaemia in this group of frail patients with frequent comorbidity. Liberal red cell transfusion in the postoperative period does not appear to improve outcome, whereas tranexamic acid appears to reduce transfusion rate at the expense of increased cardiovascular morbidity. There are encouraging results from one centre with the use of agents to stimulate red cell production, including intravenous iron and erythropoietin. UK practice differs significantly from these patients and these studies, and it is not clear whether these promising results will translate to the UK population. Methods/Design This is a single-centre randomized controlled parallel group trial, in a British university hospital.Randomization is achieved using a website and computer-generated concealed tables. Participants are 80 patients 70 years or over with acute hip fracture undergoing operative repair. The intervention group receive three daily infusions of 200 mg iron sucrose, starting within 24 hours of admission. The control group receive standard hospital care at the discretion of the clinical team. Red cell transfusions for each group are given in accordance with standard clinical triggers. The primary outcome is an increase in mean reticulocyte count in the intervention group at day 7. Secondary outcome measures include haemoglobin concentrations, early and late transfusion rates, infectious and cardiovascular complications, mobility and 30-day mortality. Discussion This is a pilot study to demonstrate haematopoietic efficacy of intravenous iron in this setting. Hence, we have chosen to measure change in reticulocyte count rather than the more clinically relevant differences in haemoglobin concentration or transfusion rate. If our results are positive, the study will provide the necessary information for development of a full-scale trial of intravenous iron. Trial registration Current Controlled Trials ISRCTN76424792; UK Medicines and Healthcare products Regulatory Authority (EuDRACT: 2011-003233-34)

Epidemiological surveillance, virulence and public health significance of Listeria spp. from drinking water

Epidemiological surveillance of drinking water from Punjab, India reported occurrence of Listeria spp. in 58.67% of Municipal Corporation (MC), 51.38% submersible pump and 12.5% hand pumps and Escherichia coli in 53.71% of MC, 29.16% submersible pump and none of samples from hand pumps. There was no positive correlation between the simultaneous occurrence of Listeria spp. and E. coli (P < 0.005; R2 = 0.89). Isolates were identified serologically and confirmed by polymerase chain reaction (PCR) amplification using specific primers targeting a 1200 bp fragment of the 16S rRNA gene. All isolates of Listeria spp. were haemolytic on 5% sheep blood agar and positive for congo dye uptake and showed multiple drug resistance, multiple antibiotic resistance (MAR) indices of 0.86 (> 0.2). One isolate of Listeria spp. was molecularly identified by sequencing of 16S rRNA gene, and its gene sequence was submitted to National Center for Biotechnology Information (NCBI) under accession no. JF798637. Using this isolate, histopathological studies were carried out and It caused significant histopathological and ultrastructural alterations in experimentally infected BALB/c mice. The conventional methods cannot predict the presence of these potentially enteropathogenic microorganisms in drinking water and hence represents a serious public health concern.Key words: Epidemiological, Listeria spp., haemolytic, serologically histopathological, multiple antibiotic resistance (MAR)

Feedback from the heart: emotional learning and memory is controlled by cardiac cycle, interoceptive accuracy and personality

Feedback processing is critical to trial-and-error learning. Here, we examined whether interoceptive signals concerning the state of cardiovascular arousal influence the processing of reinforcing feedback during the learning of ‘emotional’ face-name pairs, with subsequent effects on retrieval. Participants (N = 29) engaged in a learning task of face-name pairs (fearful, neutral, happy faces). Correct and incorrect learning decisions were reinforced by auditory feedback, which was delivered either at cardiac systole (on the heartbeat, when baroreceptors signal the contraction of the heart to the brain), or at diastole (between heartbeats during baroreceptor quiescence). We discovered a cardiac influence on feedback processing that enhanced the learning of fearful faces in people with heightened interoceptive ability. Individuals with enhanced accuracy on a heartbeat counting task learned fearful face-name pairs better when feedback was given at systole than at diastole. This effect was not present for neutral and happy faces. At retrieval, we also observed related effects of personality: First, individuals scoring higher for extraversion showed poorer retrieval accuracy. These individuals additionally manifested lower resting heart rate and lower state anxiety, suggesting that attenuated levels of cardiovascular arousal in extraverts underlies poorer performance. Second, higher extraversion scores predicted higher emotional intensity ratings of fearful faces reinforced at systole. Third, individuals scoring higher for neuroticism showed higher retrieval confidence for fearful faces reinforced at diastole. Our results show that cardiac signals shape feedback processing to influence learning of fearful faces, an effect underpinned by personality differences linked to psychophysiological arousal

Informed about Informed Consent: A Qualitative Study of Ethics Education

Informed consent is a foundational concept in modern medicine. Despite physicians’ ethical and legal obligations to obtain informed consent, no standard curriculum exists to teach residents relevant knowledge and skills. This paper presents a qualitative study of residents at one academic medical center. The authors conducted focus groups with trainees in the Departments of Internal Medicine, Emergency Medicine, and Ob/Gyn and analyzed their responses using rigorous qualitative methods. Four themes emerged: First, participants agreed that informed consent and decision-making capacity were relevant in many clinical situations. Second, participants varied widely in their understandings of consent. Third, current resident training was insufficient. Fourth, more training was needed. These results add to the growing literature that ethics education in residency is desired and useful. The findings will help educators craft instruments assessing the prevalence and degree of deficiencies related to informed consent competencies and aid in the development of a model curriculum

Exploring the relationship of sleep, cognition, and cortisol in sickle cell disease

Background: Neurocognitive impairment is common in people with Sickle Cell Disease (SCD) and evidence is accumulating that sleep disturbances play a role. The interaction between cortisol and sleep in the general population is associated with cognition as well as general wellbeing but there are few data in SCD. We aimed to understand the relationship between cortisol and sleep in individuals with SCD and explored associations with cognition. Methods: Forty-five participants of black heritage (SCD: N = 27, 9–29 years, 16 females; Controls: N = 18, 11–25 years, 13 females) were recruited from the community between 2018 - 2020. Participants completed standardized questionnaires about their sleep behaviour and wore actigraphy MotionWatch8 for 7 nights to assess nocturnal sleep patterns. Salivary cortisol samples were taken on wakening and 3 times after 14:00. Cognition was assessed using the Wechsler Intelligence Scales for children and adults. Results: People with SCD took longer to fall asleep and experienced greater wake bouts, mobile minutes and fragmented sleep compared to controls. Although non-significant, people with SCD experienced lower morning cortisol, with a flattened diurnal cortisol ratio compared to controls. Interestingly, SCD participants, but not controls, with low diurnal variation scored lowest on processing speed (PSI) and perceptual reasoning index (PRI). A moderator analysis revealed that the effect of morning cortisol and diurnal cortisol ratio on PRI by group health (i.e., SCD and healthy controls) depended on sleep quality. Discussion: Sleep and cortisol may play a crucial role in the expression of cognitive difficulties seen in SCD. This should be considered for the development of interventions to optimise cognitive functioning and sleep. This, in turn, could positively impact on secretion of cortisol and general health in SCD

Plum modulates Myoglianin and regulates synaptic function in D. melanogaster

Alterations in the neuromuscular system underlie several neuromuscular diseases and play critical roles in the development of sarcopenia, the age-related loss of muscle mass and function. Mammalian Myostatin (MST) and GDF11, members of the TGF-β superfamily of growth factors, are powerful regulators of muscle size in both model organisms and humans. Myoglianin (MYO), the Drosophila homologue of MST and GDF11, is a strong inhibitor of synaptic function and structure at the neuromuscular junction in flies. Here, we identified Plum, a transmembrane cell surface protein, as a modulator of MYO function in the larval neuromuscular system. Reduction of Plum in the larval body-wall muscles abolishes the previously demonstrated positive effect of attenuated MYO signalling on both muscle size and neuromuscular junction structure and function. In addition, downregulation of Plum on its own results in decreased synaptic strength and body weight, classifying Plum as a (novel) regulator of neuromuscular function and body (muscle) size. These findings offer new insights into possible regulatory mechanisms behind ageing- and disease-related neuromuscular dysfunctions in humans and identify potential targets for therapeutic interventions

Femoral Nerve Block Intervention in Neck of Femur Fracture (FINOF): a randomized controlled trial

Objective Fractured neck of femur is a severely painful condition with significant mortality and morbidity. We investigated whether early and continuous use of femoral nerve block can improve pain on movement and mobility after surgery in older participants with fragility neck of femur fracture. Design Prospective single centre, randomised controlled pragmatic trial. Setting Secondary care, acute NHS Trust, UK. Participants Participants admitted with a history and examination suggesting fractured neck of femur. Intervention Immediate continuous femoral nerve block via catheter or standard analgesia. Results One hundred and forty one participants were recruited, with 23 excluded. No significant difference was detected between cumulative dynamic pain scores (standard care (n = 56) vs 4 intervention (n = 55) 20 (IQR 15-24) vs 20 (15-23) p=0.51) or cumulated ambulation scores (standard care vs intervention 6 (5-9) vs 7 (5-10) p=0.76). There were no statistically different differences in secondary outcomes except cumulative pain at rest: 5 (0.5-6.5) in the standard care group and 2 (0-5) in the intervention group (p=0.043). Conclusions Early application of continuous femoral nerve block compared with standard systemic analgesia did not result in improved dynamic pain scores or superior post-operative ambulation. This technique may provide superior pain relief at rest. Continuous femoral nerve block did not delay initial control of pain, or mobilisation after surgery

How children eat may contribute to rising levels of obesity children's eating behaviours: An intergenerational study of family influences

The term ‘obesogenic environment’ is rapidly becoming part of common phraseology. However, the influence of the family and the home environment on children's eating behaviours is little understood. Research that explores the impact of this micro environment and intergenerational influences affecting children's eating behaviours is long overdue. A qualitative, grounded theory approach, incorporating focus groups and semi-structured interviews, was used to investigate the family environment and specifically, the food culture of different generations within families. What emerged was a substantive theory based on ‘ordering of eating’ that explains differences in eating behaviours within and between families. Whereas at one time family eating was highly ordered and structured, typified by the grandparent generation, nowadays family eating behaviours are more haphazard and less ordered, evidenced by the way the current generation of children eat. Most importantly, in families with an obese child eating is less ordered compared with those families with a normal weight child. Ordering of eating' is a unique concept to emerge. It shows that an understanding of the eating process is crucial to the development and improvement of interventions targeted at addressing childhood obesity within the family context

Potential benefits of medium chain fatty acids in aging and neurodegenerative disease

Neurodegenerative diseases are a large class of neurological disorders characterized by progressive dysfunction and death of neurones. Examples include Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Aging is the primary risk factor for neurodegeneration; individuals over 65 are more likely to suffer from a neurodegenerative disease, with prevalence increasing with age. As the population ages, the social and economic burden caused by these diseases will increase. Therefore, new therapies that address both aging and neurodegeneration are imperative. Ketogenic diets (KDs) are low carbohydrate, high-fat diets developed initially as an alternative treatment for epilepsy. The classic ketogenic diet provides energy via long-chain fatty acids (LCFAs); naturally occurring medium chain fatty acids (MCFAs), on the other hand, are the main components of the medium-chain triglyceride (MCT) ketogenic diet. MCT-based diets are more efficient at generating the ketone bodies that are used as a secondary energy source for neurones and astrocytes. However, ketone levels alone do not closely correlate with improved clinical symptoms. Recent findings suggest an alternative mode of action for the MCFAs, e.g., via improving mitochondrial biogenesis and glutamate receptor inhibition. MCFAs have been linked to the treatment of both aging and neurodegenerative disease via their effects on metabolism. Through action on multiple disease-related pathways, MCFAs are emerging as compounds with notable potential to promote healthy aging and ameliorate neurodegeneration. MCFAs have been shown to stimulate autophagy and restore mitochondrial function, which are found to be disrupted in aging and neurodegeneration. This review aims to provide insight into the metabolic benefits of MCFAs in neurodegenerative disease and healthy aging. We will discuss the use of MCFAs to combat dysregulation of autophagy and mitochondrial function in the context of “normal” aging, Parkinson’s disease, amyotrophic lateral sclerosis and Alzheimer’s disease

Trialling technologies to reduce hospital in‐patient falls: an agential realist analysis

This paper analyses the 'failure' of a patient safety intervention. Our study was part of an RCT of bed and bedside chair pressure sensors linked to radio pagers to prevent bedside falls in older people admitted to hospital. We use agential realism within science and technology studies to examine the fall and its prevention as a situated phenomenon of knowledge that is made and unmade through intra-actions between environment, culture, humans and technologies. We show that neither the intervention (the pressure sensor system), nor the outcome (fall prevention) could be disentangled from the broader sociomaterial context of the ward, the patients, the nurses and (especially) their work through the RCT. We argue that the RCT design, by virtue of its unacknowledged assumptions, played a part in creating the negative findings. The study also raises wider questions about the kind of subjectivities, agencies and power relations these entanglements might effect and (re)produce in the hospital ward