Harnessing the potential of data-driven strategies to optimise transfusion practice.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.

e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.

BACKGROUND: During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent. METHODS: A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research. RESULTS: Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions. CONCLUSION: e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.

An investigation to determine the normal 1st to 5th metatarsal peak pressure and PTI ratio of the forefoot.

BACKGROUND: The foot support has been described as that of a tripod. Biomechanical studies often report on peak pressures and pressure time integrals under specific areas of the foot. Reference needs to be made to the normal tripod distribution especially in the forefoot. In the forefoot the ratio between the 1st metatarsal and the 5th metatarsal on the medial and lateral columns of the foot respectively provide an excellent reference especially if the normal ratio is known. This study provides conclusive evidence of the 1st to 5th metatarsal ratio for peak pressures and pressure time integrals in the normal foot to be used as a reference. METHODS: A group of normal healthy volunteers (n = 12) and a group of patients with unilateral end stage hallux rigidus (n = 17) were recruited. Repeated measures of 1st and 5th metatarsal peak pressures and Pressure time integrals were measured to determine reliability of measurement and to provide a reference normal ratio. RESULTS: In the healthy volunteer group, the 1st/5th metatarsal ratio for PTI was very close to 1 while it was just over 1.5 for peak pressure. In patients with unilateral end stage hallux rigidus, in the normal foot the 1st/5th metatarsal ratio for PP and PTI was very close to 1. These ratios were reproduced in the operated foot following 1st MTPJ replacement. CONCLUSION: This study using normal healthy volunteers and patients undergoing 1st MTPJ replacement has demonstrated that the normal 1st/5th metatarsal peak pressure and pressure time integrals should be close to 1.

Medical management of severe obstructive sleep apnoea in two cases during the coronavirus disease 2019 pandemic.

OBJECTIVE: Severe paediatric obstructive sleep apnoea in typically developing children with adenotonsillar hypertrophy is primarily managed surgically. Non-emergency ENT surgery was paused early in the coronavirus disease 2019 pandemic and children were offered medical management for obstructive sleep apnoea. METHODS: A service evaluation was performed to assess the impact of continuous positive airway pressure alongside medical management for severe obstructive sleep apnoea. RESULTS: Over 5 months during 2020, in a tertiary care setting, two children (one boy and one girl), aged 2.7 years and 4.1 years, were offered continuous positive airway pressure and medical treatments for severe obstructive sleep apnoea whilst surgery was paused during the coronavirus disease 2019 pandemic. Both children failed to establish continuous positive airway pressure therapy because of ongoing disturbed sleep on ventilation, and they proceeded to adenotonsillectomy. Sleep-Related Breathing Disorder scale scores improved following surgical intervention. CONCLUSION: Continuous positive airway pressure therapy is poorly tolerated in children with severe obstructive sleep apnoea secondary to adenotonsillar hypertrophy. Surgery remains the most appropriate treatment.

Masters of the manipulator: two new hypocrealean genera, Niveomyces (Cordycipitaceae) and Torrubiellomyces (Ophiocordycipitaceae), parasitic on the zombie ant fungus Ophiocordyceps camponoti-floridani.

During surveys in central Florida of the zombie-ant fungus Ophiocordyceps camponoti-floridani, which manipulates the behavior of the carpenter ant Camponotus floridanus, two distinct fungal morphotypes were discovered associated with and purportedly parasitic on O. camponoti-floridani. Based on a combination of unique morphology, ecology and phylogenetic placement, we discovered that these morphotypes comprise two novel lineages of fungi. Here, we propose two new genera, Niveomyces and Torrubiellomyces, each including a single species within the families Cordycipitaceae and Ophiocordycipitaceae, respectively. We generated de novo draft genomes for both new species and performed morphological and multi-loci phylogenetic analyses. The macromorphology and incidence of both new species, Niveomyces coronatus and Torrubiellomyces zombiae, suggest that these fungi are mycoparasites since their growth is observed exclusively on O. camponoti-floridani mycelium, stalks and ascomata, causing evident degradation of their fungal hosts. This work provides a starting point for more studies into fungal interactions between mycopathogens and entomopathogens, which have the potential to contribute towards efforts to battle the global rise of plant and animal mycoses. Citation: Araújo JPM, Lebert BM, Vermeulen S, et al. 2022. Masters of the manipulator: two new hypocrealean general, Niveomyces (Cordycipitaceae) and Torrubiellomyces (Ophiocordycipitaceae), parasitic on the zombie ant fungus Ophiocordyceps camponoti-floridani. Persoonia 49: 171-194. https://doi.org/10.3767/persoonia.2022.49.05.

A prospective clinical and biomechanical analysis of feet following first metatarsophalangeal joint replacement.

BACKGROUND: There is a lack of research providing a biomechanical outcome following 1st MTPJ replacement for hallux rigidus. Despite this, 1st MTPJ replacement continues to be an alternative surgical option to fusion for this painful debilitating condition. Several studies do consider the patient reported outcomes which are subjective. RESEARCH QUESTION: The objective of this study is to provide an in depth biomechanical analysis to examine the effects of 1st MTPJ replacement for hallux rigidus on gait mechanics. METHODS: Kinematic data was collected at our CMAS (Clinical Movement Analysis Society) UK accredited gait laboratory during the gait cycle together with pressure plate pressure readings and a validated patient outcome measure before surgery and at 6 and 12 months after surgery. A complete literature review is performed. RESULTS: Kinematic data revealed a significant increase in stride length, cadence and velocity following 1st MTPJ replacement for hallux rigidus. Foot kinematic data revealed significantly reduced tibia-hindfoot abduction and pronation and reduced hindfoot-forefoot supination and adduction. There was no effect on 1st MTPJ weight bearing range of motion. Pressure plate data revealed an increase in peak pressure and pressure time integral towards the 1st metatarsal following surgery. There was a significant improvement in the patient reported outcome measure. SIGNIFICANCE: This study has demonstrated objectively that following 1st MTPJ replacement, biomechanically, a restoration of the foot posture to allow medialisation of foot pressures towards the medial column and normalisation of gait including an increase in the stride length, cadence and velocity and that clinically, there was an improvement in the MOXFQ.

Born on U.S. Soil: Access to Healthcare for Neonates of Non-Citizens.

INTRODUCTION: The 14th amendment of the United States (US) Constitution guarantees citizenship to infants born in the US. With documentation of citizenship, typically through a birth certificate, neonates gain official identity and the opportunity to qualify for services like healthcare. Most guidance on caring for immigrant children assumes that access to health care is guaranteed for babies born in the US. In practice, some infants born to non-citizen mothers face barriers in obtaining services fundamental to neonatal health. METHODS: We conducted a review of the literature to identify articles on access to care for infants born to non-citizen mothers in the US. Because of the scarcity of relevant peer-reviewed published literature on this topic, the search was broadened to grey literature including news articles, online articles, and legal reviews. Using these aggregated sources, we created a framework for understanding maternal immigration status and barriers to healthcare for neonates born in the US. We discuss risk factors from the public health, historical and ethical perspectives. RESULTS: Barriers exist for some mother-infant dyads in obtaining services such as healthcare, health insurance and supplemental nutrition programs. At-risk dyads include neonates of undocumented immigrants and birth tourists as well as neonates born to women on visas. The impact of these barriers on health-seeking behaviors, access to care, and health outcomes for these neonates is largely unknown. DISCUSSION: The framework for understanding challenges of non-citizen mothers and their infants that we present in this article provides a resource for physicians and public health professionals serving this population. That much of the literature exists outside of healthcare highlights the need for more scholarly work on this problem. Future research will better inform advocacy and public health efforts to protect this vulnerable population of newborn citizens and their mothers.

Zombie-ant fungi cross continents: II. Myrmecophilous hymenostilboid species and a novel zombie lineage.

Ophiocordyceps species infecting ants are globally distributed, with diversity concentrated in the tropics and decreasing with increasing latitude. Among these myrmecophilous species, the ones exhibiting the ability to manipulate host behavior, the so-called "zombie-ant fungi" of the O. unilateralis clade, have been studied progressively over the last decade. However, we know very little about other myrmecophilous groups, such as species within the Ophiocordyceps subgenus Neocordyceps. Species within this group exhibit Hymenostilbe asexual morphs with the ascospores readily breaking into part-spores and regularly kill their hosts on the forest floor, with few records of behavioral manipulation. Here, we describe five new species of Ophiocordyceps belonging to the subgenus Neocordyceps infecting ants in the rainforests of the Brazilian Amazon and Ghana and analyze their ability to manipulate host behavior. We also propose a new status for a species previously described as a variety, providing its phylogenetic placement for the first time. The species proposed herein can readily be separated using classic taxonomic criteria, and this is further supported by ecological and molecular multiloci data.

Magnetic properties of (Fe1-xMnx)2AlB2 and the impact of substitution on the magnetocaloric effect.

In this work, we investigate the magnetic structures of (Fe1-xMnx)2AlB2 solid-solution quaternaries in the x=0 to 1 range using x-ray and neutron diffraction, magnetization measurements, and mean-field theory calculations. While Fe2AlB2 and Mn2AlB2 are known to be ferromagnetic (FM) and antiferromagnetic (AFM), respectively, herein we focused on the magnetic structure of their solid solutions, which is not well understood. The FM ground state of Fe2AlB2 becomes a canted AFM at x≈0.2, with a monotonically diminishing FM component until x≈0.5. The FM transition temperature (TC) decreases linearly with increasing x. These changes in magnetic moments and structures are reflected in anomalous expansions of the lattice parameters, indicating a magnetoelastic coupling. Lastly, the magnetocaloric properties of the solid solutions were explored. For x=0.2 the isothermal entropy change is smaller by 30% than it is for Fe2AlB2, while the relative cooling power is larger by 6%, due to broadening of the temperature range of the transition.

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records.

BACKGROUND: The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. METHODS: We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). RESULTS: From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. CONCLUSIONS: While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management.

The acoustic emission from asperity interactions in mixed lubrication.

Gears typically operate in mixed lubrication conditions, where the lubricant film is too thin to prevent opposing surface asperities from interacting with each other. The likelihood/intensity of interactions is indicated by the Λ ratio: the ratio of smooth surface film thickness to surface roughness. Researchers have asserted that asperity interactions are the predominant cause of acoustic emission (AE) in healthy gear contacts. However, direct experiments on gears have yet to yield a clear relationship between the Asperity AE (AAE) and Λ ratio, this is in part due to the complexity of gear tooth contacts. In this paper, a disc rig was used to simulate a simplified gear contact so that the fundamental relationship between AAE and Λ could be investigated more effectively. By varying oil temperature and entrainment speed, a wide spectrum of lubrication conditions was generated. In contrast to other published studies, an independent measurement technique, the contact voltage (CV), was used to verify the amount of interactions, and repeated roughness measurements were used to confirm minimal surface wear. A simple, consistent and precise relationship between AAE amplitude and Λ was identified and defined for changes from full-film to mixed lubrication. Within the mixed lubrication regime, the AAE amplitude increased exponentially as Λ decreased at all speeds tested. It was also observed that an increase in speed always resulted in an increase in AAE amplitude, independently of any changes in Λ. This direct effect of speed was modelled so that the AAE could be predicted for any combination of speed and Λ within the tested envelope. This paper links gear contact tribology and AE with new precision and clearly demonstrates the potential of using AAE as a sensitive monitoring technique for the lubrication condition of gears.

A consecutive, prospective analysis of the Rotoglide 1st metatarsophalangeal joint replacement.

Following 1st metatarsophalangeal joint replacement, there is a normalisation of foot pressure distribution as demonstrated by peak pressures of the 1st and 5th metatarsal heads and their ratio as measured by pedobarographs. This compares favourably with the unaffected foot. Functional dorsiflexion range of motion is maintained and there is a significant improvement in the reported patient outcome measure.

Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records.

BACKGROUND: Macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use. METHODOLOGY: Observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia. RESULTS: Analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular. CONCLUSIONS: Although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.

What Attracts Medical Students to Primary Care? A Nominal Group Evaluation.

OBJECTIVE: To examine the perceptions of first-year medical students on their experiences in primary care. METHODS: Nominal group technique sessions were conducted with first-year medical students for 5 years. Questions were designed to evaluate primary care experiences and the role of primary care physicians. The questions explored what would make them consider primary care, what would detract from it, and what primary care has to offer that no other specialty can. Responses were weighted and ranked. The main outcome was the top five responses to three questions that were obtained at each session. RESULTS: Thirty-four students generated 280 responses to 3 questions. The top 5 responses for each year resulted in 29 experiences that strengthen enthusiasm: patient interactions (weighted sum, 43%), physician interactions/role modeling (22%), community interactions (20%), healthcare system/finances (8%), and other (6%). The top 5 responses resulted in 26 experiences that weaken enthusiasm, including hidden curriculum (45%), poor role models (29%), uncertainties about the healthcare system such as finances and documentation (20%), and patient interactions (6%). The top 5 responses regarding the uniqueness of primary care resulted in 37 experiences, including patient interactions (38%), continuity of care (20%), knowledge base (13%), community impact (10%), lifestyle benefits (10%), and education/prevention (9%). CONCLUSIONS: Medical students highlighted unique relationships with patients and continuity of care as experiences that increase their enthusiasm for primary care. Negative experiences that weakened enthusiasm for primary care included hidden curriculum and poor role models. Programs that provide experiences in primary care can increase student interest in primary care careers.

Zombie-ant fungi across continents: 15 new species and new combinations within Ophiocordyceps. I. Myrmecophilous hirsutelloid species.

Ophiocordyceps species infecting ants - the so-called zombie-ant fungi - comprise one of the most intriguing and fascinating relationships between microbes and animals. They are widespread within tropical forests worldwide, with relatively few reports from temperate ecosystems. These pathogens possess the ability to manipulate host behaviour in order to increase their own fitness. Depending on the fungal species involved the infected ants are manipulated either to leave the nest to ascend understorey shrubs, to die biting onto vegetation, or descend from the canopy to die at the base of trees. Experimental evidence has demonstrated that the behavioural change aids spore dispersal and thus increases the chances of infection, because of the existing behavioural immunity expressed inside ant colonies that limits fungal development and transmission. Despite their undoubted importance for ecosystem functioning, these fungal pathogens are still poorly documented, especially regarding their diversity, ecology and evolutionary relationships. Here, we describe 15 new species of Ophiocordyceps with hirsutella-like asexual morphs that exclusively infect ants. These form a monophyletic group that we identified in this study as myrmecophilous hirsutelloid species. We also propose new combinations for species previously described as varieties and provide for the first time important morphological and ecological information. The species proposed herein were collected in Brazil, Colombia, USA, Australia and Japan. All species could readily be separated using classic taxonomic criteria, in particular ascospore and asexual morphology.

Epitypification and re-description of the zombie-ant fungus, Ophiocordyceps unilateralis (Ophiocordycipitaceae).

The type of Ophiocordyceps unilateralis (Ophiocordycipitaceae, Hypocreales, Ascomycota) is based on an immature specimen collected on an ant in Brazil. The host was identified initially as a leaf-cutting ant (Atta cephalotes, Attini, Myrmicinae). However, a critical examination of the original illustration reveals that the host is the golden carpenter ant, Camponotus sericeiventris (Camponotini, Formicinae). Because the holotype is no longer extant and the original diagnosis lacks critical taxonomic information - specifically, on ascus and ascospore morphology - a new type from Minas Gerais State of south-east Brazil is designated herein. A re-description of the fungus is provided and a new phylogenetic tree of the O. unilateralis clade is presented. It is predicted that many more species of zombie-ant fungi remain to be delimited within the O. unilateralis complex worldwide, on ants of the tribe Camponotini.

Experimental and Numerical Study of Micropitting Initiation in Real Rough Surfaces in a Micro-elastohydrodynamic Lubrication Regime.

Micropitting is a form of surface fatigue damage that happens at the surface roughness scale in lubricated contacts in commonly used machine elements, such as gears and bearings. It occurs where the specific film thickness (ratio of smooth surface film thickness to composite surface roughness) is sufficiently low for the contacts to operate in the mixed lubrication regime, where the load is in part carried by direct asperity contacts. Micropitting is currently seen as a greater issue for gear designers than is regular pitting fatigue failure as the latter can be avoided by control of steel cleanliness. This paper describes the results of both theoretical and experimental studies of the onset of micropitting in test disks operated in the mixed lubrication regime. A series of twin disk mixed-lubrication experiments were performed in order to examine the evolution of micropitting damage during repeated cyclic loading of surface roughness asperities as they pass through the contact. Representative measurements of the surfaces used in the experimental work were then evaluated using a numerical model which combines a transient line contact micro-elastohydrodynamic lubrication (micro-EHL) simulation with a calculation of elastic sub-surface stresses. This model generated time-history of stresses within a block of material as it passes through the contact, based on the instantaneous surface contact pressure and traction at each point in the computing mesh at each timestep. This stress time-history was then used within a shear-strain-based fatigue model to calculate the cumulative damage experienced by the surface due to the loading sequence experienced during the experiments. The proposed micro-EHL model results and the experimental study were shown to agree well in terms of predicting the number of loading cycles that are required for the initial micropitting to occur.

Case Report: Free Latissimus Dorsi Flap in Combination With Subdural Space Reduction for the Prevention of Recurrent Hemorrhage Following Hemispherectomy.

BACKGROUND AND IMPORTANCE: Extensive cerebral resections for the treatment of epilepsy may result in a large intracranial dead space that is prone to recurrent hemorrhage, either due to mechanical dislodgement or the development of extensive subdural membranes. Several techniques have been proposed to decrease the risk of hemorrhage by either reducing or filling the remaining intracranial dead space. CLINICAL PRESENTATION: We present a case of persistent hemorrhage following functional hemispherectomy in a patient with a large porencephalic cyst. A treatment strategy involving both subdural space reduction and cranial vault filling with a vascularized free latissimus dorsi flap is discussed. CONCLUSION: Subdural space reduction and cranial vault filling with a vascularized free latissimus dorsi flap is a viable treatment alternative in patients with large areas of intracranial dead space.