Consumer-driven evaluation of assistive technology usage and perceived value in people with myositis in Australia.

INTRODUCTION: Idiopathic inflammatory myopathies (known as 'myositis') are a group of rare sporadic inflammatory muscle disorders that significantly impact function and quality of life. There are no standardised approaches in the use of assistive technologies in myositis. This study was initiated to investigate current use and perceived value of assistive technology (AT) by people with myositis. METHODS: A cross-sectional online questionnaire (Qualtrics) was designed to capture information regarding AT use and perceived value and demographic information from people with myositis across Australia. The questionnaire was distributed via the Myositis Association of Australia and specialist myositis clinics. Participants were asked to identify which AT items they owned and how frequently the item was used and to rate the 'usefulness' of those items. Information was also collected on participants' engagement with health professionals regarding assistive technologies. CONSUMER AND COMMUNITY INVOLVEMENT: Consumer involvement via the Myositis Research Consumer Panel identified a knowledge gap regarding AT. The questionnaire was designed with consumer input and review. RESULTS: One hundred two people (102) with myositis completed the questionnaire. One hundred (100) participants owned at least one AT device, with a median of 12.5 items and a maximum of 65 items. The most used devices were associated with toileting, personal care and mobility. Participants rated AT devices relating to environmental support, sleeping, seating and body support as most useful. There was a positive correlation between disease duration and number of devices used (r2 = 0.248, p = 0.012). Majority of participants (75.5%) were interested in talking to health professionals about AT; however, only 50% had done so. CONCLUSION: AT device usage is high among people with myositis, with most items deemed to be useful. Greater occupational therapy input into recommendations and potential funding options may improve knowledge and access to AT.

Evaluating the druggability of TrmD, a potential antibacterial target, through design and microbiological profiling of a series of potent TrmD inhibitors.

The post-transcriptional modifier tRNA-(N1G37) methyltransferase (TrmD) has been proposed to be essential for growth in many Gram-negative and Gram-positive pathogens, however previously reported inhibitors show only weak antibacterial activity. In this work, optimisation of fragment hits resulted in compounds with low nanomolar TrmD inhibition incorporating features designed to enhance bacterial permeability and covering a range of physicochemical space. The resulting lack of significant antibacterial activity suggests that whilst TrmD is highly ligandable, its essentiality and druggability are called into question.

Discovery and structure-activity relationships of a novel oxazolidinone class of bacterial type II topoisomerase inhibitors.

There is an increasingly urgent and unmet medical need for novel antibiotic drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. Novel bacterial type II topoisomerase inhibitors (NBTIs) are of high interest due to limited cross-resistance with fluoroquinolones, however analogues with Gram-negative activity often suffer from hERG channel inhibition. A novel series of bicyclic-oxazolidinone inhibitors of bacterial type II topoisomerase were identified which display potent broad-spectrum anti-bacterial activity, including against MDR strains, along with an encouraging in vitro safety profile. In vivo proof of concept was achieved in a A. baumannii mouse thigh infection model.

Development and pilot evaluation of an educational session to support sparing opioid prescriptions to opioid naïve patients in a Canadian primary care setting.

BACKGROUND: Prescribing rates of some analgesics decreased during the public health crisis. Yet, up to a quarter of opioid-naïve persons prescribed opioids for noncancer pain develop prescription opioid use disorder. We, therefore, sought to evaluate a pilot educational session to support primary care-based sparing of opioid analgesics for noncancer pain among opioid-naïve patients in British Columbia (BC). METHODS: Therapeutics Initiative in BC has launched an audit and feedback intervention. Individual prescribing portraits were mailed to opioid prescribers, followed by academic detailing webinars. The webinars' learning outcomes included defining the terms opioid naïve and opioid sparing, and educating attendees on the (lack of) evidence for opioid analgesics to treat noncancer pain. The primary outcome was change in knowledge measured by four multiple-choice questions at the outset and conclusion of the webinar. RESULTS: Two hundred participants attended four webinars; 124 (62%) responded to the knowledge questions. Community-based primary care professionals (80/65%) from mostly urban settings (77/62%) self-identified as family physicians (46/37%), residents (22/18%), nurse practitioners (24/19%), and others (32/26%). Twelve participants (10%) recalled receiving the individualized portraits. While the correct identification of opioid naïve definitions increased by 23%, the correct identification of opioid sparing declined by 7%. Knowledge of the gaps in high-quality evidence supporting opioid analgesics and risk tools increased by 26% and 35%, respectively. CONCLUSION: The educational session outlined in this pilot yielded mixed results but appeared acceptable to learners and may need further refinement to become a feasible way to train professionals to help tackle the current toxic drugs crisis.

Dynamical analysis of the infection status in diverse communities due to COVID-19 using a modified SIR model.

In this article, we model and study the spread of COVID-19 in Germany, Japan, India and highly impacted states in India, i.e., in Delhi, Maharashtra, West Bengal, Kerala and Karnataka. We consider recorded data published in Worldometers and COVID-19 India websites from April 2020 to July 2021, including periods of interest where these countries and states were hit severely by the pandemic. Our methodology is based on the classic susceptible-infected-removed (SIR) model and can track the evolution of infections in communities, i.e., in countries, states or groups of individuals, where we (a) allow for the susceptible and infected populations to be reset at times where surges, outbreaks or secondary waves appear in the recorded data sets, (b) consider the parameters in the SIR model that represent the effective transmission and recovery rates to be functions of time and (c) estimate the number of deaths by combining the model solutions with the recorded data sets to approximate them between consecutive surges, outbreaks or secondary waves, providing a more accurate estimate. We report on the status of the current infections in these countries and states, and the infections and deaths in India and Japan. Our model can adapt to the recorded data and can be used to explain them and importantly, to forecast the number of infected, recovered, removed and dead individuals, as well as it can estimate the effective infection and recovery rates as functions of time, assuming an outbreak occurs at a given time. The latter information can be used to forecast the future basic reproduction number and together with the forecast on the number of infected and dead individuals, our approach can further be used to suggest the implementation of intervention strategies and mitigation policies to keep at bay the number of infected and dead individuals. This, in conjunction with the implementation of vaccination programs worldwide, can help reduce significantly the impact of the spread around the world and improve the wellbeing of people.

Restoring carbapenem efficacy: a novel carbapenem companion targeting metallo-ß-lactamases in carbapenem-resistant Enterobacterales.

BACKGROUND: The dissemination of MBLs compromises effective use of many ß-lactams in the treatment of patients with life-threatening bacterial infections. Predicted global increases in the prevalence of MBL-producing carbapenem-resistant Enterobacterales (CRE) are being realized, yielding infections that are untreatable with existing therapies including newly approved ß-lactam/ß-lactamase inhibitor combinations. Developing MBL inhibitors (MBLIs) now is essential to address the growing threat that MBL-producing CRE pose to patients. METHODS: A novel MBLI series was assessed by susceptibility testing and time-kill assays. Target activity and selectivity was evaluated using bacterial NDM, VIM and IMP enzyme assays and human matrix metallopeptidase enzyme assays, respectively, and cytotoxicity was assessed in HepG2 cells. In vivo efficacy of meropenem/MBLI combinations was evaluated in a mouse thigh infection model using an NDM-1-producing Escherichia coli strain. RESULTS: Combination of MBLIs with carbapenems reduced MICs for NDM/IMP/VIM-producing Enterobacterales by up to 128-fold compared with the carbapenems alone. Supplementation of meropenem with the promising compound 272 reduced the MIC90 from 128 to 0.25 mg/L in a panel of MBL-producing CRE clinical isolates (n = 115). Compound 272 restored the bactericidal activity of meropenem and was non-cytotoxic, potentiating the antimicrobial action of meropenem through specific inhibition of NDM, IMP and VIM. In vivo efficacy was achieved in a mouse thigh infection model with meropenem/272 dosed subcutaneously. CONCLUSIONS: We have developed a series of rationally designed MBLIs that restore activity of carbapenems against NDM/IMP/VIM-producing Enterobacterales. This series warrants further development towards a novel combination therapy that combats antibiotic-resistant organisms, which pose a critical threat to human health.

Team-based care Evaluation and Adoption Model (TEAM) Framework: Supporting the comprehensive evaluation of primary care transformation over time.

OBJECTIVE: To introduce the new Team-based care Evaluation and Adoption Model (TEAM) Framework. QUALITY OF EVIDENCE: The initial TEAM Framework was derived from a series of reviews and consultations with academic and clinical experts. In a parallel process, team-based primary and community care evaluation in Canada was assessed through a structured review of academic literature, followed by a review of policy literature of existing primary care evaluation frameworks. MAIN MESSAGE: The review of academic articles alongside an analysis of policy documents and existing evaluation frameworks in primary care resulted in the development of the 10-dimension TEAM Framework. CONCLUSION: Primary care transformation requires evaluation over time. The TEAM Framework provides a comprehensive framework for assessing evidence needed to support short- and long-term actionable improvements for team-based primary and community care in Canada. This framework will inform the development of an evaluation tool kit for primary care teams.

Structural and mechanistic analysis of ATPase inhibitors targeting mycobacterial DNA gyrase.

OBJECTIVES: To evaluate the efficacy of two novel compounds against mycobacteria and determine the molecular basis of their action on DNA gyrase using structural and mechanistic approaches. METHODS: Redx03863 and Redx04739 were tested in antibacterial assays, and also against their target, DNA gyrase, using DNA supercoiling and ATPase assays. X-ray crystallography was used to determine the structure of the gyrase B protein ATPase sub-domain from Mycobacterium smegmatis complexed with the aminocoumarin drug novobiocin, and structures of the same domain from Mycobacterium thermoresistibile complexed with novobiocin, and also with Redx03863. RESULTS: Both compounds, Redx03863 and Redx04739, were active against selected Gram-positive and Gram-negative species, with Redx03863 being the more potent, and Redx04739 showing selectivity against M. smegmatis. Both compounds were potent inhibitors of the supercoiling and ATPase reactions of DNA gyrase, but did not appreciably affect the ATP-independent relaxation reaction. The structure of Redx03863 bound to the gyrase B protein ATPase sub-domain from M. thermoresistibile shows that it binds at a site adjacent to the ATP- and novobiocin-binding sites. We found that most of the mutations that we made in the Redx03863-binding pocket, based on the structure, rendered gyrase inactive. CONCLUSIONS: Redx03863 and Redx04739 inhibit gyrase by preventing the binding of ATP. The fact that the Redx03863-binding pocket is distinct from that of novobiocin, coupled with the lack of activity of resistant mutants, suggests that such compounds could have potential to be further exploited as antibiotics.

Dynamic tracking with model-based forecasting for the spread of the COVID-19 pandemic.

In this paper, a susceptible-infected-removed (SIR) model has been used to track the evolution of the spread of COVID-19 in four countries of interest. In particular, the epidemic model, that depends on some basic characteristics, has been applied to model the evolution of the disease in Italy, India, South Korea and Iran. The economic, social and health consequences of the spread of the virus have been cataclysmic. Hence, it is imperative that mathematical models can be developed and used to compare published datasets with model predictions. The predictions estimated from the presented methodology can be used in both the qualitative and quantitative analysis of the spread. They give an insight into the spread of the virus that the published data alone cannot, by updating them and the model on a daily basis. We show that by doing so, it is possible to detect the early onset of secondary spikes in infections or the development of secondary waves. We considered data from March to August, 2020, when different communities were affected severely and demonstrate predictions depending on the model's parameters related to the spread of COVID-19 until the end of December, 2020. By comparing the published data with model results, we conclude that in this way, it may be possible to reflect better the success or failure of the adequate measures implemented by governments and authorities to mitigate and control the current pandemic.

A SIR model assumption for the spread of COVID-19 in different communities.

In this paper, we study the effectiveness of the modelling approach on the pandemic due to the spreading of the novel COVID-19 disease and develop a susceptible-infected-removed (SIR) model that provides a theoretical framework to investigate its spread within a community. Here, the model is based upon the well-known susceptible-infected-removed (SIR) model with the difference that a total population is not defined or kept constant per se and the number of susceptible individuals does not decline monotonically. To the contrary, as we show herein, it can be increased in surge periods! In particular, we investigate the time evolution of different populations and monitor diverse significant parameters for the spread of the disease in various communities, represented by China, South Korea, India, Australia, USA, Italy and the state of Texas in the USA. The SIR model can provide us with insights and predictions of the spread of the virus in communities that the recorded data alone cannot. Our work shows the importance of modelling the spread of COVID-19 by the SIR model that we propose here, as it can help to assess the impact of the disease by offering valuable predictions. Our analysis takes into account data from January to June, 2020, the period that contains the data before and during the implementation of strict and control measures. We propose predictions on various parameters related to the spread of COVID-19 and on the number of susceptible, infected and removed populations until September 2020. By comparing the recorded data with the data from our modelling approaches, we deduce that the spread of COVID-19 can be under control in all communities considered, if proper restrictions and strong policies are implemented to control the infection rates early from the spread of the disease.

Design, synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase.

According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled. As a result, novel approaches to treating broad-spectrum bacterial infections are of vital importance. During the course of our wider efforts to discover unique methods of targeting multidrug-resistant (MDR) pathogens, we identified a novel series of amide-linked pyrimido[4,5-b]indol-8-amine inhibitors of bacterial type II topoisomerases. Compounds from the series were highly potent against gram-positive bacteria and mycobacteria, with excellent potency being retained against a panel of relevant Mycobacterium tuberculosis drug-resistant clinical isolates.

Do acute hospitalised patients in Australia have a different body mass index to the general Australian population: a point prevalence study?

Objective The aim of the present study was to provide a current snapshot of the body mass index (BMI) of the entire patient cohort of an Australian tertiary hospital on one day and compare these data with current published Australian and state (Western Australia) population norms. Methods A single-centre prospective point prevalence study was performed whereby BMI was calculated following actual measurement of patient weight (nurse) and height (physiotherapist) on one day during 2015. Variables were summarised descriptively, and one-way analysis of variance was used to investigate the relationship between continuous BMI and hospital speciality. Multivariate Cox proportional hazards regression was used to analyse the time to leaving hospital, where those who died were censored at their date of death. Results Data were collected from 416 patients (96% of the hospital population on that day). The mean (± s.e.m.) BMI across the whole hospital population was 26.6±2.2kgm-2, with 37% of patients having normal BMI, 8% being underweight, 32% being overweight, 19% being obese and 4% being severely obese. Comparison with both national and state population norms for 2014-15 reflected higher proportions of the hospital population in the underweight and extremely obese categories, and lower proportions in the overweight and obese categories. There was no significant difference in BMI across medical specialties. Conclusions Despite health warnings about the direct relationship between illness and being overweight or obese, the results of the present study reveal fewer hospitalised patients in these BMI categories and more underweight patients than in the non-hospitalised general Australian population. Being overweight or obese may offer some protection against hospitalisation, but there is a point where the deleterious effect of obesity results in more extremely obese individuals being hospitalised than the proportion represented in the general population. What is known about the topic? Although there is significant current published data relating to general Australian population BMI, there is little pertaining specifically to the hospitalised population. Accordingly, although we know that as an affluent Western country we are seeing growing rates of overweight and obese people and relatively few underweight or undernourished people in the general population, we do not know whether these trends are mirrored or magnified in those who are sick in hospital. We also know that although caring for obese patients carries a significant burden, there is the suggestion in some healthcare literature of an 'obesity paradox', whereby in certain disease states being overweight actually decreases mortality and promotes a faster recovery from illness compared with underweight people, who have poorer outcomes. What does this paper add? This paper is the first of its kind to actually measure and calculate the BMI of a whole tertiary Australian hospital population and provide some comparison with published Australian norms. On average, the hospital cohort was overweight, with a mean (± s.e.m.) BMI of 26.6±2.2kgm-2, but less so than the general population, which had a mean BMI of 27.5±0.2kgm-2. The results also indicate that compared with state and national norms, underweight and extremely obese patients were over-represented in the hospitalised cohort, whereas overweight or obese patients were under-represented. What are the implications for practitioners? Although only a single-centre study, the case-mix and socioeconomic catchment area of the hospital evaluated in the present study suggest that it is a typical tertiary urban West Australian facility and, as such, there may be some implications for practitioners. Primarily, administrators need to ensure that we are able to accommodate people of increasing weight in our hospital facilities and have the resources with which to do so, because, on average, hospitalised patients were overweight. In addition, resources need to be available for managing the extremely obese if numbers in this subset of the population increase. Finally, practitioners may also need to consider that although the management of underweight and undernourished patients may be less of a physical burden, there are actually more of these patients in hospital compared with the general population, and they may require a different package of resource utilisation.

Novel Bacterial Topoisomerase Inhibitors with Potent Broad-Spectrum Activity against Drug-Resistant Bacteria.

The novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that does not have cross-resistance with the quinolones. Here, we report the evaluation of the in vitro properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms and Mycobacterium tuberculosis No cross-resistance with fluoroquinolone-resistant Staphylococcus aureus and E. coli isolates was observed. Measured MIC90 values were 4 and 8 µg/ml against a panel of contemporary multidrug-resistant isolates of Acinetobacter baumannii and E. coli, respectively. In addition, representative compounds exhibited greater antibacterial potency than the quinolones against obligate anaerobic species. Spontaneous mutation rates were low, with frequencies of resistance typically <10-8 against E. coli and A. baumannii at concentrations equivalent to 4-fold the MIC. Compound-resistant E. coli mutants that were isolated following serial passage were characterized by whole-genome sequencing and carried a single Arg38Leu amino acid substitution in the GyrA subunit of DNA gyrase. Preliminary in vitro safety data indicate that the series shows a promising therapeutic index and potential for low human ether-a-go-go-related gene (hERG) inhibition (50% inhibitory concentration [IC50], >100 µM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable in vitro safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents.

In vitro biological evaluation of novel broad-spectrum isothiazolone inhibitors of bacterial type II topoisomerases.

OBJECTIVES: To evaluate the in vitro biological properties of a novel class of isothiazolone inhibitors of the bacterial type II topoisomerases. METHODS: Inhibition of DNA gyrase and topoisomerase IV activity was assessed using DNA supercoiling and decatenation assays. MIC and MBC were determined according to CLSI guidelines. Antibacterial combinations were assessed using a two-dimensional chequerboard MIC method. Spontaneous frequency of resistance was measured at various multiples of the MIC. Resistant mutants were generated by serial passage at subinhibitory concentrations of antibacterials and genetic mutations were determined through whole genome sequencing. Mammalian cytotoxicity was evaluated using the HepG2 cell line. RESULTS: Representative isothiazolone compound REDX04957 and its enantiomers (REDX05967 and REDX05990) showed broad-spectrum bactericidal activity against the ESKAPE organisms, with the exception of Enterococcus spp., as well as against a variety of other human bacterial pathogens. Compounds retained activity against quinolone-resistant strains harbouring GyrA S83L and D87G mutations (MIC ≤4 mg/L). Compounds inhibited the supercoiling activity of wild-type DNA gyrase and the decatenation function of topoisomerase IV. Frequency of resistance of REDX04957 at 4× MIC was <9.1 × 10(-9). Against a panel of recent MDR isolates, REDX05967 demonstrated activity against Acinetobacter baumannii with MIC50 and MIC90 of 16 and 64 mg/L, respectively. Compounds showed a lack of cytotoxicity against HepG2 cells at 128 mg/L. CONCLUSIONS: Isothiazolone compounds show potent activity against Gram-positive and -negative pathogens with a dual targeting mechanism-of-action and a low potential for resistance development, meriting their continued investigation as broad-spectrum antibacterial agents.

YPTB3816 of Yersinia pseudotuberculosis strain IP32953 is a virulence-related metallo-oligopeptidase.

BACKGROUND: Although bacterial peptidases are known to be produced by various microorganisms, including pathogenic bacteria, their role in bacterial physiology is not fully understood. In particular, oligopeptidases are thought to be mainly involved in degradation of short peptides e.g. leader peptides released during classical protein secretion pathways. The aim of this study was to investigate effects of inactivation of an oligopeptidase encoding gene opdA gene of Yersinia pseudotuberculosis on bacterial properties in vivo and in vitro, and to test dependence of the enzymatic activity of the respective purified enzyme on the presence of different divalent cations. RESULTS: In this study we found that oligopeptidase OpdA of Yersinia pseudotuberculosis is required for bacterial virulence, whilst knocking out the respective gene did not have any effect on bacterial viability or growth rate in vitro. In addition, we studied enzymatic properties of this enzyme after expression and purification from E. coli. Using an enzyme depleted of contaminant divalent cations and different types of fluorescently labelled substrates, we found strong dependence of its activity on the presence of particular cations. Unexpectedly, Zn2+ showed stimulatory activity only at low concentrations, but inhibited the enzyme at higher concentrations. In contrast, Co2+, Ca2+ and Mn2+ stimulated activity at all concentrations tested, whilst Mg2+ revealed no effect on the enzyme activity at all concentrations used. CONCLUSIONS: The results of this study provide valuable contribution to the investigation of bacterial peptidases in general, and that of metallo-oligopeptidases in particular. This is the first study demonstrating that opdA in Yersinia pseudotuberculsosis is required for pathogenicity. The data reported are important for better understanding of the role of OpdA-like enzymes in pathogenesis in bacterial infections. Characterisation of this protein may serve as a basis for the development of novel antibacterials based on specific inhibition of this peptidase activity.

Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors.

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.

Poly(ε-lysine) dendrons as modulators of quorum sensing in Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa is a significant contributor to recalcitrant multi-drug resistant infections. In a vigorous search for alternative therapeutic approaches, the communication system used by this bacterium to synchronise the expression of genes involved in pathogenicity has been identified as a potential target. Poly(ε-lysine) dendrons, composed of three branching generations, were examined herein for their anti-virulence potential and ability to disperse within P. a eruginosa biofilms. These hyperbranched macromolecules reduced attachment and biomass production under different nutrient growth conditions, and at concentrations that were not lethal to planktonic cells (0.2, 0.4 and 0.8 mg/mL). Fluorescent labelling revealed the intracellular localisation and cell-penetrating capacity of the dendron, and showed the rapid uptake and release of unexploited dendron from pre-established P. a eruginosa biofilms. Additionally, the dendron induced complete attenuation of LasA protease, a marker of quorum sensing inactivation, by preventing its accumulation in the external environment. This study thus demonstrates the anti-virulence potential of this class of macromolecules, and could represent a novel therapeutic approach for the treatment of antibiotic-resistant P. a eruginosa infections.

Tick hazard in the South Downs National Park (UK): species, distribution, key locations for future interventions, site density, habitats.

Background: South Downs National Park (SDNP) is UK's most visited National Park, and a focus of tick-borne Lyme disease. The first presumed UK autochthonous cases of tick-borne encephalitis and babesiosis were recorded in 2019-20. SDNP aims to conserve wildlife and encourage recreation, so interventions are needed that reduce hazard without negatively affecting ecosystem health. To be successful these require knowledge of site hazards. Methods: British Deer Society members submitted ticks removed from deer. Key potential intervention sites were selected and six 50 m2 transects drag-sampled per site (mostly twice yearly for 2 years). Ticks were identified in-lab (sex, life stage, species), hazard measured as tick presence, density of ticks (all life stages, DOT), and density of nymphs (DON). Sites and habitat types were analysed for association with hazard. Distribution was mapped by combining our results with records from five other sources. Results: A total of 87 Ixodes ricinus (all but one adults, 82% F) were removed from 14 deer (10 Dama dama; three Capreolus capreolus; one not recorded; tick burden, 1-35) at 12 locations (commonly woodland). Five key potential intervention sites were identified and drag-sampled 2015-16, collecting 623 ticks (238 on-transects): 53.8% nymphs, 42.5% larvae, 3.7% adults (13 M, 10 F). Ticks were present on-transects at all sites: I. ricinus at three (The Mens (TM); Queen Elizabeth Country Park (QECP); Cowdray Estate (CE)), Haemaphysalis punctata at two (Seven Sisters Country Park (SSCP); Ditchling Beacon Nature Reserve (DBNR)). TM had the highest DOT at 30/300 m2 (DON = 30/300 m2), followed by QECP 22/300 m2 (12/300 m2), CE 8/300 m2 (6/300 m2), and SSCP 1/300 m2 (1/300 m2). For I. ricinus, nymphs predominated in spring, larvae in the second half of summer and early autumn. The overall ranking of site hazard held for DON and DOT from both seasonal sampling periods. DBNR was sampled 2016 only (one adult H. punctata collected). Woodland had significantly greater hazard than downland, but ticks were present at all downland sites. I. ricinus has been identified in 33/37 of SDNPs 10 km2 grid squares, Ixodes hexagonus 10/37, H. punctata 7/37, Dermacentor reticulatus 1/37. Conclusions: Mapping shows tick hazard broadly distributed across SDNP. I. ricinus was most common, but H. punctata's seeming range expansion is concerning. Recommendations: management of small heavily visited high hazard plots (QECP); post-visit precaution signage (all sites); repellent impregnated clothing for deerstalkers; flock trials to control H. punctata (SSCP, DBNR). Further research at TM may contribute to knowledge on ecological dynamics underlying infection density and predator re-introduction/protection as public health interventions. Ecological research on H. punctata would aid control. SDNP Authority is ideally placed to link and champion policies to reduce hazard, whilst avoiding or reducing conflict between public health and ecosystem health.

Does inspiratory muscle training improve lung function and quality of life in people with inclusion body myositis? A pilot study.

Inclusion body myositis is the most common acquired myositis in adults, predominantly weakening forearm flexor and knee extensor muscles. Subclinical respiratory muscle weakness has recently been recognised in people with inclusion body myositis, increasing their risk of respiratory complications. Inspiratory muscle training, a technique which demonstrates efficacy and safety in improving respiratory function in people with neuromuscular disorders, has never been explored in those with inclusion body myositis. In this pilot study, six adults with inclusion body myositis (age range 53 to 81 years) completed eight weeks of inspiratory muscle training. Measures of respiratory function, quality of life, sleep quality and a two-minute walk test were performed pre and post-intervention. All participants improved their respiratory function, with maximal inspiratory pressure, sniff nasal inspiratory pressure and forced vital capacity increasing by an average of 50 % (p = .002), 43 % (p = .018) and 13 % (p = .003) respectively. No significant change was observed in quality of life, sleep quality or two-minute walk test performance. No complications occurred due to inspiratory muscle training This pilot study provides the first evidence that inspiratory muscle training may be safe and effective in people with Inclusion Body Myositis, potentially mitigating the complications of poor respiratory function.

Descriptive analysis and evaluation of Health Link referrals to the emergency department before and during the COVID-19 pandemic.

BACKGROUND: In Alberta, Health Link (HL) provides a 24-h, nurse-staffed, phone resource to the public for health-care advice. HL directs callers to either seek care in the emergency department (ED), with a primary care provider or provide self-care at home. This work aims to describe HL ED referrals prior to and during the COVID-19 pandemic. METHODS: Data from January 1, 2018-December 31, 2019, and July 1, 2020-June 30, 2022, were selected. HL calls were categorized as likely appropriate if the patient was referred and presented to the ED within 24 h and had a Canadian Triage and Acuity Scale (CTAS) of 1-3; or a CTAS of 4-5 and the patient was admitted, specialist consulted, or diagnostic imaging or laboratory tests were completed. The primary outcome was the percentage of likely appropriate referrals among all HL ED referrals. RESULTS: In the 2018-2019 and 2020-2022 samples, respectively, there were 845,372 and 832,730 calls. Of the 211,723 and 213,486 ED referrals, only 140,614 (66.4%) and 143,322 (67.1%) presented to an ED. Of these, 84.3 and 86.7 per 100 patient visits were categorized as likely appropriate referrals. Health Link referrals account for 3.2% and 3.8% of all ED visits. IMPACT: HL referrals to the ED represent only a small percentage of all ED visits. Based on our definition, most referrals by HL are likely appropriate. The COVID-19 pandemic does not appear to have altered the rates of calls to HL, the number of HL calls referred to the ED, nor the likely appropriateness of those referrals.