The Checkpoint Program: collaborative care to reduce the reliance of frequent presenters on ED

Introduction: Growing pressures upon Emergency Departments [ED] call for new ways of working with frequent presenters who, although small in number, place extensive demands on services, to say nothing of the costs and consequences for the patients themselves. EDs are often poorly equipped to address the multi-dimensional nature of patient need and the complex circumstances surrounding repeated presentation. Employing a model of intensive short-term community-based case management, the Checkpoint program sought to improve care coordination for this patient group, thereby reducing their reliance on ED. Method: This study employed a single group interrupted time series design, evaluating patient engagement with the program and year-on-year individual differences in the number of ED visits pre and post enrolment. Associated savings were also estimated. Results: Prior to intervention, there were two dominant modes in the ED presentation trends of patients. One group had a steady pattern with ≥7 presentations in each of the last four years. The other group had an increasing trend in presentations, peaking in the 12 months immediately preceding enrolment. Following the intervention, both groups demonstrated two consecutive year-on-year reductions. By the second year, and from an overall peak of 22.5 presentations per patient per annum, there was a 53% reduction in presentations. This yielded approximate savings of $7100 per patient. Discussion: Efforts to improve care coordination, when combined with proactive case management in the community, can impact positively on ED re-presentation rates, provided they are concerted, sufficiently intensive and embed the principles of integration. Conclusion: The Checkpoint program demonstrated sufficient promise to warrant further exploration of its sustainability. However, health services have yet to determine the ideal organisational structures and funding arrangements to support such initiativ

Subcellular localisation of Medicago truncatula 9/13-hydroperoxide lyase reveals a new localisation pattern and activation mechanism for CYP74C enzymes

<p>Abstract</p> <p>Background</p> <p>Hydroperoxide lyase (HPL) is a key enzyme in plant oxylipin metabolism that catalyses the cleavage of polyunsaturated fatty acid hydroperoxides produced by the action of lipoxygenase (LOX) to volatile aldehydes and oxo acids. The synthesis of these volatile aldehydes is rapidly induced in plant tissues upon mechanical wounding and insect or pathogen attack. Together with their direct defence role towards different pathogens, these compounds are believed to play an important role in signalling within and between plants, and in the molecular cross-talk between plants and other organisms surrounding them. We have recently described the targeting of a seed 9-HPL to microsomes and putative lipid bodies and were interested to compare the localisation patterns of both a 13-HPL and a 9/13-HPL from <it>Medicago truncatula</it>, which were known to be expressed in leaves and roots, respectively.</p> <p>Results</p> <p>To study the subcellular localisation of plant 9/13-HPLs, a set of YFP-tagged chimeric constructs were prepared using two <it>M. truncatula </it>HPL cDNAs and the localisation of the corresponding chimeras were verified by confocal microscopy in tobacco protoplasts and leaves. Results reported here indicated a distribution of <it>M</it>.<it>truncatula </it>9/13-HPL (HPLF) between cytosol and lipid droplets (LD) whereas, as expected, <it>M</it>.<it>truncatula </it>13-HPL (HPLE) was targeted to plastids. Notably, such endocellular localisation has not yet been reported previously for any 9/13-HPL. To verify a possible physiological significance of such association, purified recombinant HPLF was used in activation experiments with purified seed lipid bodies. Our results showed that lipid bodies can fully activate HPLF.</p> <p>Conclusion</p> <p>We provide evidence for the first CYP74C enzyme, to be targeted to cytosol and LD. We also showed by sedimentation and kinetic analyses that the association with LD or lipid bodies can result in the protein conformational changes required for full activation of the enzyme. This activation mechanism, which supports previous <it>in vitro </it>work with synthetic detergent micelle, fits well with a mechanism for regulating the rate of release of volatile aldehydes that is observed soon after wounding or tissue disruption.</p

Treatable traits in the NOVELTY study

Background and objective: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent and complex diseases that require personalized management. Although a strategy based on treatable traits (TTs) has been proposed, the prevalence and relationship of TTs to the diagnostic label and disease severity established by the attending physician in a real-world setting are unknown. We assessed how the presence/absence of specific TTs relate to the diagnosis and severity of ‘asthma’, ‘COPD’ or ‘asthma + COPD’. Methods: The authors selected 30 frequently occurring TTs from the NOVELTY study cohort (NOVEL observational longiTudinal studY; NCT02760329), a large (n = 11,226), global study that systematically collects data in a real-world setting, both in primary care clinics and specialized centres, for patients with ‘asthma’ (n = 5932, 52.8%), ‘COPD’ (n = 3898, 34.7%) or both (‘asthma + COPD’; n = 1396, 12.4%). Results: The results indicate that (1) the prevalence of the 30 TTs evaluated varied widely, with a mean ± SD of 4.6 ± 2.6, 5.4 ± 2.6 and 6.4 ± 2.8 TTs/patient in those with ‘asthma’, ‘COPD’ and ‘asthma + COPD’, respectively (p < 0.0001); (2) there were no large global geographical variations, but the prevalence of TTs was different in primary versus specialized clinics; (3) several TTs were specific to the diagnosis and severity of disease, but many were not; and (4) both the presence and absence of TTs formed a pattern that is recognized by clinicians to establish a diagnosis and grade its severity. Conclusion: These results provide the largest and most granular characterization of TTs in patients with airway diseases in a real-world setting to date

Validation of a diagnosis-agnostic symptom questionnaire for asthma and/or COPD

ACKNOWLEDGEMENTS The authors wish to acknowledge the work of the NOVELTY study investigators, who are listed in full in the supplementary material, and Sharon MacLachlan (Evidera, London, UK), who participated in the analysis of sections of the data. Medical writing support, under the direction of the authors, was provided by Lauren McNally, MSci, CMC Connect, McCann Health Medical Communications, and was funded by AstraZeneca, Cambridge, UK, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015; 163: 461–464). Support statement: The NOVELTY study is funded by AstraZenecaPeer reviewedPublisher PD

Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?

Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown. Objective: To assess hypothalamic–pituitary–gonadal axis, muscle volume and function 5 years after pubertal induction. Methods: A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2 years) then evaluated at +2.5 years and +5 y ears (final follow-up ~3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function, and limb muscle MRI. Results: Participants were 18.7 years (s.d. 1.6) at the final follow-up and had been on GC for 11.2 years (s.d. 2.2). Testosterone levels were similar at +2.5 years (8.6 nmol /L (s.d. 3.4) and 5 years (11.0 nmol/L (s.d. 6.1). TV increased from 2.8 mL ( s.d. 0.9) at +2 years to 7.1 mL (s.d. 1.8) then 10.6 mL (s.d. 3.5) at +2.5 years and +5.0 years (P < 0.001). Inhibin B levels increased from 55.6 pg/mL (s.d. 47.0) at baseline to 158.2 pg/mL ( s.d. 87.6), P =0.004 at 5 years but remained lower than reference values (mean 305 pg/mL). Muscle contractile bulk decreased. Interpretation: Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in inhibin B, TV, and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle, and well-being, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important

Cluster analyses from the real-world NOVELTY study : six clusters across the asthma COPD spectrum

Funding The NOVELTY study is funded by AstraZeneca. ACKNOWLEDGMENTS The authors would like to thank the patients who participated in this study and the NOVELTY Scientific Community and the NOVELTY study investigators who are listed in full in Tables E7 and E8 in the Online Repository. Medical writing support, under the direction of the authors, was provided by Richard Knight, PhD, CMC Connect, a division of IPG Health Medical Communications, funded by AstraZeneca in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med. 2022;175[9]:1298-1304). J. Vestbo is supported by the NIHR Manchester Biomedical Research Centre and the NIHR Manchester Clinical Research FacilityPeer reviewedPublisher PD

Polymyalgia Rheumatica (PMR) Special Interest Group at OMERACT 11: outcomes of importance for patients with PMR

We worked toward developing a core outcome set for clinical research studies in polymyalgia rheumatica (PMR) by conducting (1) patient consultations using modified nominal group technique; (2) a systematic literature review of outcome measures in PMR; (3) a pilot observational study of patients presenting with untreated PMR, and further discussion with patient research partners; and (4) a qualitative focus group study of patients with PMR on the meaning of stiffness, using thematic analysis. (1) Consultations included 104 patients at 4 centers. Symptoms of PMR included pain, stiffness, fatigue, and sleep disturbance. Function, anxiety, and depression were also often mentioned. Participants expressed concerns about diagnostic delay, adverse effects of glucocorticoids, and fear of relapse. (2) In the systematic review, outcome measures previously used for PMR include pain visual analog scores (VAS), morning stiffness, blood markers, function, and quality of life; standardized effect sizes posttreatment were large. (3) Findings from the observational study indicated that asking about symptom severity at 7 AM, or "on waking," appeared more relevant to disease activity than asking about symptom severity "now" (which depended on the time of assessment). (4) Preliminary results were presented from the focus group qualitative study, encompassing broad themes of stiffness, pain, and the effect of PMR on patients' lives. It was concluded that further validation work is required before a core outcome set in PMR can be recommended. Nevertheless, the large standardized effect sizes suggest that pain VAS is likely to be satisfactory as a primary outcome measure for assessing response to initial therapy of PMR. Dissection of between-patient heterogeneity in the subsequent treatment course may require attention to comorbidity as a potential confounding factor

Heterogeneity within and between physician-diagnosed asthma and/or COPD : NOVELTY cohort

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Magnetic resonance imaging protocols for paediatric neuroradiology

Increasingly, radiologists are encouraged to have protocols for all imaging studies and to include imaging guidelines in care pathways set up by the referring clinicians. This is particularly advantageous in MRI where magnet time is limited and a radiologist’s review of each patient’s images often results in additional sequences and longer scanning times without the advantage of improvement in diagnostic ability. The difficulties of imaging small children and the challenges presented to the radiologist as the brain develops are discussed. We present our protocols for imaging the brain and spine of children based on 20 years experience of paediatric neurological MRI. The protocols are adapted to suit children under the age of 2 years, small body parts and paediatric clinical scenarios