The British Society for Rheumatology Biologics Registers in Ankylosing Spondylitis (BSRBR-AS) study: Protocol for a prospective cohort study of the long-term safety and quality of life outcomes of biologic treatment

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Axial spondyloarthropathy typically has its onset in early adulthood and can impact significantly on quality of life. In the UK, biologic anti-tumour necrosis factor therapy is recommended for patients who are unresponsive to non-steroidal anti-inflammatory drugs. There remain several unresolved issues about the long-term safety and quality of life outcomes of biologic treatment in axial spondyloarthropathy. Long-term "real-world" surveillance data are required to complement data from randomised controlled trials. METHODS/DESIGN: We are conducting a UK-wide prospective cohort study of patients with axial spondyloarthropathy who are naïve to biologic therapy at the time of recruitment. Those about to commence anti-tumour necrosis factor biologic therapy will enter a "biologic" sub-cohort with other patients assigned to a "non-biologic" sub-cohort. The primary objective is to determine whether the use of biologic therapy is associated with an increased risk of serious infection, while secondary objectives are to assess differences in malignancy, serious comorbidity, all-cause mortality but also assess impact on specific clinical domains (physical health, mental health and quality of life) including work outcomes between biologic and non-biologic patient cohorts. Patients will be followed-up for up to 5 years. Data are obtained at baseline and at standard clinical follow-up visits - at 3, 6 and 12 months and then annually for the biologic cohort and annually for the non-biologic cohort. This study will also collect biological samples for genetic analysis. DISCUSSION: Although biologic therapy is widely used for ankylosing spondylitis patients who are unresponsive to non-steroidal anti-inflammatory drugs, the majority of the available safety information comes from rheumatoid arthritis, where increased infection risk has consistently been shown. However, given the typical demographic differences between rheumatoid arthritis and axial spondyloarthropathy patients, it is important to develop an epidemiologically rigorous cohort of patients receiving biologic therapy to effectively evaluate outcomes with regard not only to safety but also to quantify benefits across clinical, psychosocial and work outcomes. CLINICAL TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was not required or obtained.BSRBR-AS is funded by the BSR, which in turn receives funding from the manufacturers of the biologic therapies included in this study (currently AbbVie, Pfizer and UCB). Pharmaceutical companies providing funds to BSR do not have a role in the oversight of the study, but they do receive advance notice of publications on which they are able to comment. They do not have access to the data collected but can request analyses of the data, for which additional funds are provided. GJM chairs a Pfizer competitive grant committee for which he receives an honorarium. GJM and GTJ have received separate funding from AbbVie and Pfizer to study spondyloarthritis in the Scotland Registry for Ankylosing Spondylitis (SIRAS) study. LK has received an unrestricted educational grant from UCB. AK has received research funding from Abbvie and Pfizer as well as speaker/chairman fees and payments for attending advisory boards from Abbvie, Pfizer and UCB. The remaining authors have no competing interests

Prospective randomized study comparing the Teleflex Medical SaphLITE Retractor to the Ethicon CardioVations Clearglide Endoscopic System

BACKGROUND: Several minimally invasive saphenous vein harvesting techniques have been developed to reduce morbidities associated with coronary artery bypass grafting. This prospective, randomized study was designed to compare two commonly used minimally invasive saphenous vein harvesting techniques, the SaphLITE Retractor System (Teleflex Medical) and the Clearglide Endoscopic Vessel Harvesting System (Ethicon CardioVations, Inc.). METHODS: Between January 2003 and March 2004, a total of 200 patients scheduled for primary, nonemergent coronary artery bypass grafting, with or without concomitant procedures were randomized into two groups: SaphLITE (n = 100) and Clearglide (n = 100). Pre-, intra- and postoperative data was collected and subjected to statistical analysis. Randomization provided homogenous groups with respect to preoperative risk factors. RESULTS: Harvest location for the SaphLITE group was thigh (n = 40), lower leg (n = 5) and both lower leg and thigh (n = 55). The location of harvest for the Clearglide group was thigh (n = 3), lower leg (n = 16) and both lower leg and thigh (n = 81). The mean incision length was 3.6 cm (range, 2–6) in the SaphLITE group versus 2.1 cm (range, 1–4) in the Clearglide group (p < 0.05). The total incision length was 12.9 cm versus 8.9 (p < 0.05) in the SaphLITE and Clearglide groups. Conversion to the open technique occurred in 5 SaphLITE patients and 7 Clearglide patients. Intraoperative leg exploration for bleeding occurred in two of the Clearglide patients and none of the SaphLITE patients. Post-operative complications specifically related to minimally invasive harvesting technique, including a two-week post-discharge visit, were not statistically different between the groups. CONCLUSION: The saphenous vein can be safely harvested utilizing the SaphLITE and Clearglide systems. While the Clearglide system allows for fewer incisions (number and length) and less harvest time, these benefits may be outweighed by the increased cost of the Clearglide system compared to the SaphLITE retractor

Glial Hsp70 Protects K+ Homeostasis in the Drosophila Brain during Repetitive Anoxic Depolarization

Neural tissue is particularly vulnerable to metabolic stress and loss of ion homeostasis. Repetitive stress generally leads to more permanent dysfunction but the mechanisms underlying this progression are poorly understood. We investigated the effects of energetic compromise in Drosophila by targeting the Na+/K+-ATPase. Acute ouabain treatment of intact flies resulted in subsequent repetitive comas that led to death and were associated with transient loss of K+ homeostasis in the brain. Heat shock pre-conditioned flies were resistant to ouabain treatment. To control the timing of repeated loss of ion homeostasis we subjected flies to repetitive anoxia while recording extracellular [K+] in the brain. We show that targeted expression of the chaperone protein Hsp70 in glial cells delays a permanent loss of ion homeostasis associated with repetitive anoxic stress and suggest that this is a useful model for investigating molecular mechanisms of neuroprotection

ATP signalling in epilepsy

This paper focuses on a role for ATP neurotransmission and gliotransmission in the pathophysiology of epileptic seizures. ATP along with gap junctions propagates the glial calcium wave, which is an extraneuronal signalling pathway in the central nervous system. Recently astrocyte intercellular calcium waves have been shown to underlie seizures, and conventional antiepileptic drugs have been shown to attenuate these calcium waves. Blocking ATP-mediated gliotransmission, therefore, represents a potential target for antiepileptic drugs. Furthermore, while knowledge of an antiepileptic role for adenosine is not new, a recent study showed that adenosine accumulates from the hydrolysis of accumulated ATP released by astrocytes and is believed to inhibit distant synapses by acting on adenosine receptors. Such a mechanism is consistent with a surround-inhibitory mechanism whose failure would predispose to seizures. Other potential roles for ATP signalling in the initiation and spread of epileptiform discharges may involve synaptic plasticity and coordination of synaptic networks. We conclude by making speculations about future developments

Measurement of J/ψ -pair production in pp collisions at √s = 13 TeV and study of gluon transverse-momentum dependent PDFs

The production cross-section of J/ψ pairs in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV is measured using a data sample corresponding to an integrated luminosity of 4.2 fb−1 collected by the LHCb experiment. The measurement is performed with both J/ψ mesons in the transverse momentum range 0 &lt; pT&lt; 14 GeV/c and rapidity range 2.0 &lt; y &lt; 4.5. The cross-section of this process is measured to be 16.36 ± 0.28 (stat) ± 0.88 (syst) nb. The contributions from single-parton scattering and double-parton scattering are separated based on the dependence of the cross-section on the absolute rapidity difference ∆y between the two J/ψ mesons. The effective cross-section of double-parton scattering is measured to be σeff = 13.1 ± 1.8 (stat) ± 2.3 (syst) mb. The distribution of the azimuthal angle ϕCS of one of the J/ψ mesons in the Collins-Soper frame and the pT-spectrum of the J/ψ pairs are also measured for the study of the gluon transverse-momentum dependent distributions inside protons. The extracted values of ⟨cos 2ϕCS⟩ and ⟨cos 4ϕCS⟩ are consistent with zero, but the presence of azimuthal asymmetry at a few percent level is allowed