The utility of implantable loop recorders in patient management: an age- and indication-stratified study in the outpatient-implant era

INTRODUCTION: Implantable loop recorders (ILR) are now routinely implanted for long-term cardiac monitoring in the clinic setting. This study examined the real-world performance of these devices, focusing on the management decision changes made in response to ILR-recorded data. METHODS AND RESULTS: This was a single centre, prospective observational study of consecutive patients undergoing ILR implantation. All patients who underwent implantation of a Medtronic Reveal LINQ device from September 2017 to June 2019 at Barts Heart Centre were included.501 patients were included. 302 (60%) patients underwent ILR implantation for an indication of pre-syncope/syncope, 96 (19%) for palpitations, 72 (14%) for atrial fibrillation (AF) detection with a history of cryptogenic stroke and 31 (6%) for patients deemed to be high risk of serious cardiac arrhythmia.The primary outcome of this study was that an ILR-derived diagnosis altered management in 110 (22%) of patients. Secondary outcomes concerned sub-group analyses by indication: in patients who presented with syncope/presyncope, a change in management resulting from ILR data was positively associated with age (HR: 1.04 [95%CI 1.02-1.06]; p < 0.001) and negatively associated with a normal ECG at baseline (HR 0.54 [0.31-0.93]; p = 0.03). Few patients (1/57, 2%) aged < 40 years in this group underwent device implantation, compared to 19/62 patients (31%) aged 75 years and over (p = 0.0024). 22/183 (12%) of patients in the 40-74 age range had a device implanted.In patients who underwent ILR insertion following cryptogenic stroke, 13/72 patients (18%) had AF detected leading to a decision to commence anticoagulation. CONCLUSION: These results inform the utility of ILR in the clinical setting. Diagnoses provided by ILR that lead to changes in management are rare in patients under age 40, particularly following syncope, presyncope or palpitations. In older patients new diagnoses are frequently made and trigger important changes in treatment

Impact testing to determine the mechanical properties of articular cartilage in isolation and on bone

The original publication is available at www.springerlink.comNon peer reviewedPostprin

Childhood tetanus in Australia: ethical issues for a should-be-forgotten preventable disease

Refusal of a parent to have a child vaccinated against tetanus raised ethical issues for the treating clinicians. The clinicians felt their duty to the child was compromised, but recognised that our society leaves the authority for such decisions with the parents. As there was no reason, other than different beliefs about vaccination, to doubt the parent\u27s care for the child, the clinicians limited their response to providing strong recommendations in favour of vaccination. Other issues raised by this case include community protection, and the costs to the community of treating a vaccine-preventable disease

Hypoxia Promotes Atrial Tachyarrhythmias via Opening of ATP-Sensitive Potassium Channels

BACKGROUND: Hypoxia-ischemia predisposes to atrial arrhythmia. Atrial ATP-sensitive potassium channel (KATP) modulation during hypoxia has not been explored. We investigated the effects of hypoxia on atrial electrophysiology in mice with global deletion of KATP pore-forming subunits. METHODS: Whole heart KATP RNA expression was probed. Whole-cell KATP current and action potentials were recorded in isolated wild-type (WT), Kir6.1 global knockout (6.1-gKO), and Kir6.2 global knockout murine atrial myocytes. Langendorff-perfused hearts were assessed for atrial effective refractory period (ERP), conduction velocity, wavefront path length (WFPL), and arrhymogenicity under normoxia/hypoxia using a microelectrode array and programmed electrical stimulation. Heart histology was assessed. RESULTS: Expression patterns were essentially identical for all KATP subunit RNA across human heart, whereas in mouse, Kir6.1 and SUR2 (sulphonylurea receptor) were higher in ventricle than atrium, and Kir6.2 and SUR1 were higher in atrium. Compared with WT, Kir6.2 global knockout atrial myocytes had reduced tolbutamide-sensitive current and action potentials were more depolarized with slower upstroke and reduced peak amplitude. Action potential duration was prolonged in 6.1-gKO atrial myocytes, absent of changes in other ion channel gene expression or atrial myocyte hypertrophy. In Langendorff-perfused hearts, baseline atrial ERP was prolonged and conduction velocity reduced in both KATP knockout mice compared with WT, without histological fibrosis. Compared with baseline, hypoxia led to conduction velocity slowing, stable ERP, and WFPL shortening in WT and 6.1-gKO hearts, whereas WFPL was stable in Kir6.2 global knockout hearts due to ERP prolongation with conduction velocity slowing. Tolbutamide reversed hypoxia-induced WFPL shortening in WT and 6.1-gKO hearts through ERP prolongation. Atrial tachyarrhythmias inducible with programmed electrical stimulation during hypoxia in WT and 6.1-gKO mice correlated with WFPL shortening. Spontaneous arrhythmia was not seen. CONCLUSIONS: KATP block/absence leads to cellular and tissue level atrial electrophysiological modification. Kir6.2 global knockout prevents hypoxia-induced atrial WFPL shortening and atrial arrhythmogenicity to programmed electrical stimulation. This mechanism could be explored translationally to treat ischemically driven atrial arrhythmia

Targeting of the Tumor Suppressor GRHL3 by a miR-21-Dependent Proto-Oncogenic Network Results in PTEN Loss and Tumorigenesis

SummaryDespite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice, and demonstrate that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling. Restoration of Pten expression completely abrogates SCC formation. Reduced levels of GRHL3 and PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC

Evidence-based planning and costing palliative care services for children : novel multi-method epidemiological and economic exemplar

Background: Children’s palliative care is a relatively new clinical specialty. Its nature is multi-dimensional and its delivery necessarily multi-professional. Numerous diverse public and not-for-profit organisations typically provide services and support. Because services are not centrally coordinated, they are provided in a manner that is inconsistent and incoherent. Since the first children’s hospice opened in 1982, the epidemiology of life-limiting conditions has changed with more children living longer, and many requiring transfer to adult services. Very little is known about the number of children living within any given geographical locality, costs of care, or experiences of children with ongoing palliative care needs and their families. We integrated evidence, and undertook and used novel methodological epidemiological work to develop the first evidence-based and costed commissioning exemplar. Methods: Multi-method epidemiological and economic exemplar from a health and not-for-profit organisation perspective, to estimate numbers of children under 19 years with life-limiting conditions, cost current services, determine child/parent care preferences, and cost choice of end-of-life care at home. Results: The exemplar locality (North Wales) had important gaps in service provision and the clinical network. The estimated annual total cost of current children’s palliative care was about £5.5 million; average annual care cost per child was £22,771 using 2007 prevalence estimates and £2,437- £11,045 using new 2012/13 population-based prevalence estimates. Using population-based prevalence, we estimate 2271 children with a life-limiting condition in the general exemplar population and around 501 children per year with ongoing palliative care needs in contact with hospital services. Around 24 children with a wide range of life-limiting conditions require end-of-life care per year. Choice of end-of-life care at home was requested, which is not currently universally available. We estimated a minimum (based on 1 week of end-of-life care) additional cost of £336,000 per year to provide end-of-life support at home. Were end-of-life care to span 4 weeks, the total annual additional costs increases to £536,500 (2010/11 prices). Conclusions: Findings make a significant contribution to population-based needs assessment and commissioning methodology in children’s palliative care. Further work is needed to determine with greater precision which children in the total population require access to services and when. Half of children who died 2002-7 did not have conditions that met the globally used children's palliative care condition categories, which need revision in light of findings

Shadowing in Inelastic Scattering of Muons on Carbon, Calcium and Lead at Low XBj

Nuclear shadowing is observed in the per-nucleon cross-sections of positive muons on carbon, calcium and lead as compared to deuterium. The data were taken by Fermilab experiment E665 using inelastically scattered muons of mean incident momentum 470 GeV/c. Cross-section ratios are presented in the kinematic region 0.0001 < XBj <0.56 and 0.1 < Q**2 < 80 GeVc. The data are consistent with no significant nu or Q**2 dependence at fixed XBj. As XBj decreases, the size of the shadowing effect, as well as its A dependence, are found to approach the corresponding measurements in photoproduction.Comment: 22 pages, incl. 6 figures, to be published in Z. Phys.