Breathlessness and opioid prescribing in COPD in general practice: a cross-sectional, observational study.

Chronic breathlessness is a disabling syndrome, prevalent in people with advanced chronic obstructive pulmonary disease (COPD). Regular, low-dose, oral sustained-release morphine is approved in Australia to reduce symptomatic chronic breathlessness. We aimed to determine the current prescribing patterns of opioids for chronic breathlessness in COPD in Australian general practice and to define any associated patient and practitioner characteristics. Five years (2011 to 2016) of the Bettering the Evaluation and Care of Health database, an Australian national, continual, cross-sectional study of clinical care in general practice were used. The database included 100 consecutive clinical encounters from almost 1000 general practitioners annually (n=488 100 encounters). Descriptive analyses with subsequent regression models were generated. Breathlessness as a patient-defined reason for encounter was identified in 621 of 4522 encounters where COPD was managed. Opioids were prescribed in 309 of 4522 encounters where COPD was managed (6.8%; (95% CI) 6.1-7.6), of which only 17 were prescribed for breathlessness, and the rest for other conditions almost entirely related to pain. Patient age (45-64 years versus age 80+ years, OR 1.68; 1.19-2.36), Commonwealth Concession Card holders (OR 1.70; 1.23-2.34) and socioeconomic disadvantage (OR 1.30; 1.01-1.68) were associated with increased likelihood of opioid prescription at COPD encounters. The rate of opioid prescriptions rose over the 5 years of study. In primary care encounters for COPD, opioids were prescribed in 6.8% of cases, but almost never for breathlessness. These data create a baseline against which to compare changes in prescribing as the treatment of chronic breathlessness evolves

Sources of Relativistic Jets in the Galaxy

Black holes of stellar mass and neutron stars in binary systems are first detected as hard X-ray sources using high-energy space telescopes. Relativistic jets in some of these compact sources are found by means of multiwavelength observations with ground-based telescopes. The X-ray emission probes the inner accretion disk and immediate surroundings of the compact object, whereas the synchrotron emission from the jets is observed in the radio and infrared bands, and in the future could be detected at even shorter wavelengths. Black-hole X-ray binaries with relativistic jets mimic, on a much smaller scale, many of the phenomena seen in quasars and are thus called microquasars. Because of their proximity, their study opens the way for a better understanding of the relativistic jets seen elsewhere in the Universe. From the observation of two-sided moving jets it is inferred that the ejecta in microquasars move with relativistic speeds similar to those believed to be present in quasars. The simultaneous multiwavelength approach to microquasars reveals in short timescales the close connection between instabilities in the accretion disk seen in the X-rays, and the ejection of relativistic clouds of plasma observed as synchrotron emission at longer wavelengths. Besides contributing to a deeper comprehension of accretion disks and jets, microquasars may serve in the future to determine the distances of jet sources using constraints from special relativity, and the spin of black holes using general relativity.Comment: 39 pages, Tex, 8 figures, to appear in vol. 37 (1999) of Annual Reviews of Astronomy and Astrophysic

The "Artificial Mathematician" Objection: Exploring the (Im)possibility of Automating Mathematical Understanding

Reuben Hersh confided to us that, about forty years ago, the late Paul Cohen predicted to him that at some unspecified point in the future, mathematicians would be replaced by computers. Rather than focus on computers replacing mathematicians, however, our aim is to consider the (im)possibility of human mathematicians being joined by “artificial mathematicians” in the proving practice—not just as a method of inquiry but as a fellow inquirer

Analysis of dental care of children receiving comprehensive care under general anaesthesia at a teaching hospital in England

Objectives: This study aimed to analyse the characteristics of comprehensive dental care provided under general anaesthesia (CDGA) and to review the additional treatment required by children over the 6 years subsequent to CDGA. Method: Information collected from hospital records for the 6-year period following the first CDGA included the types of dental treatment performed at CDGA, the return rates for follow-up appointments, further treatment required subsequent to CDGA and the types of dental treatment performed at repeat DGA. Results: The study population consisted of 263 children, of whom 129 had a significant medical history, with mean age of 6.7 years. The results revealed that the waiting time for CDGA was significantly shorter in children who had a significant medical history, with 49 % being admitted for CDGA within 3 months of pre-GA assessment, as compared to 29 % of healthy children. 67 % of children had follow-up care recorded, with a slightly higher proportion of children with significant medical history returning for follow-up [70 % (90/129)] compared with 65 % (87/134) of healthy children. Re-treatment rates were 34 % (88/263), the majority of cases being treated under local analgesia (42/88). 34 of 263 children had repeat DGA (12.9 %). Of these 71 % (24/34) were children with significant medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children (74 %), repeat DGA was due to trauma, oral pathology, supernumerary removal, hypomineralized teeth or new caries of previously sound or un-erupted teeth at CDGA. The ratio of extraction over restoration (excluding fissure sealants) performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial CDGA. Conclusions: There was a higher ratio of extraction over restorations at the repeat DGA. This suggests that the prescribed treatments at repeat DGA were more aggressive as compared to the initial CDGA in 1997. The majority of the treatment required at repeat DGA was to treat new disease

Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases

Behavioral Problems In The Utilization Of New Technology To Control Caries: Patients And Provider Readiness And Motivation

New research developments frequently are neither adopted by providers nor utilized by patients. This dual problem of impacting the behaviors of providers and patients presents a challenge. This paper will present behavioral theories and technologies that can be utilized to impact both provider and patient behaviors

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

Background: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation

Using “Omics” and Integrated Multi-Omics Approaches to Guide Probiotic Selection to Mitigate Chytridiomycosis and Other Emerging Infectious Diseases

Emerging infectious diseases in wildlife are responsible for massive population declines. In amphibians, chytridiomycosis caused by Batrachochytrium dendrobatidis, Bd, has severely affected many amphibian populations and species around the world. One promising management strategy is probiotic bioaugmentation of antifungal bacteria on amphibian skin. In vivo experimental trials using bioaugmentation strategies have had mixed results, and therefore a more informed strategy is needed to select successful probiotic candidates. Metagenomic, transcriptomic, and metabolomic methods, colloquially called “omics,” are approaches that can better inform probiotic selection and optimize selection protocols. The integration of multiple omic data using bioinformatic and statistical tools and in silico models that link bacterial community structure with bacterial defensive function can allow the identification of species involved in pathogen inhibition. We recommend using 16S rRNA gene amplicon sequencing and methods such as indicator species analysis, the Kolmogorov–Smirnov Measure, and co-occurrence networks to identify bacteria that are associated with pathogen resistance in field surveys and experimental trials. In addition to 16S amplicon sequencing, we recommend approaches that give insight into symbiont function such as shotgun metagenomics, metatranscriptomics, or metabolomics to maximize the probability of finding effective probiotic candidates, which can then be isolated in culture and tested in persistence and clinical trials. An effective mitigation strategy to ameliorate chytridiomycosis and other emerging infectious diseases is necessary; the advancement of omic methods and the integration of multiple omic data provide a promising avenue toward conservation of imperiled species

Different atmospheric moisture divergence responses to extreme and moderate El Niños

On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST

A new rhynchocephalian from the late jurassic of Germany with a dentition that is unique amongst tetrapods.

Rhynchocephalians, the sister group of squamates (lizards and snakes), are only represented by the single genus Sphenodon today. This taxon is often considered to represent a very conservative lineage. However, rhynchocephalians were common during the late Triassic to latest Jurassic periods, but rapidly declined afterwards, which is generally attributed to their supposedly adaptive inferiority to squamates and/or Mesozoic mammals, which radiated at that time. New finds of Mesozoic rhynchocephalians can thus provide important new information on the evolutionary history of the group. A new fossil relative of Sphenodon from the latest Jurassic of southern Germany, Oenosaurus muehlheimensis gen. et sp. nov., presents a dentition that is unique amongst tetrapods. The dentition of this taxon consists of massive, continuously growing tooth plates, probably indicating a crushing dentition, thus representing a previously unknown trophic adaptation in rhynchocephalians. The evolution of the extraordinary dentition of Oenosaurus from the already highly specialized Zahnanlage generally present in derived rhynchocephalians demonstrates an unexpected evolutionary plasticity of these animals. Together with other lines of evidence, this seriously casts doubts on the assumption that rhynchocephalians are a conservative and adaptively inferior lineage. Furthermore, the new taxon underlines the high morphological and ecological diversity of rhynchocephalians in the latest Jurassic of Europe, just before the decline of this lineage on this continent. Thus, selection pressure by radiating squamates or Mesozoic mammals alone might not be sufficient to explain the demise of the clade in the Late Mesozoic, and climate change in the course of the fragmentation of the supercontinent of Pangaea might have played a major role