Calculating evidence-based renal replacement therapy – Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy – A before and after study

Background Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given “dose” can be difficult. In research, the “dose” of renal replacement therapy is given as effluent flow rate in ml kg−1 h−1. Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses of renal replacement therapy. Our aim was to design an excel calculator which would personalise patient's treatment, deliver an effective, evidence-based dose of renal replacement therapy without large variations in practice and prolong filter life. Our calculator prescribes a haemodialfiltration dose of 25 ml kg−1 h−1 whilst limiting the filtration fraction to 15%. MethodsWe compared the episodes of renal replacement therapy received by a historical group of patients, by retrieving their data stored on the haemofiltration machines, to a group where the calculator was used. In the second group, the data were gathered prospectively. ResultsThe median delivered dose reduced from 41.0 ml kg−1 h−1 to 26.8 ml kg−1 h−1 with reduced variability that was significantly closer to the aim of 25 ml kg−1.h−1 (p < 0.0001). The median treatment time increased from 8.5 h to 22.2 h (p = 0.00001). Conclusion Our calculator significantly reduces variation in prescriptions of continuous veno-venous haemodiafiltration and provides an evidence-based dose. It is easy to use and provides personal care for patients whilst optimizing continuous veno-venous haemodiafiltration delivery and treatment times

Diagnosis and initial management in psoriatic arthritis: A qualitative study with patients

Objectives. PsA is an inflammatory condition that can cause pain, fatigue, swelling and joint stiffness.The consequences include impaired physical function, a high psychosocial burden, reduced quality of life and work disability. The presenting symptoms can be non-specific and varied, leading todelays in diagnosis or referral to specialist teams. The aim of this study was to explore patients’ experiences of being diagnosed and the initial management of PsA.Methods. The study used a qualitative design, with data collected in one-to-one, face-to-face semistructured interviews.Results. Fifteen newly diagnosed patients (less than 24 months) from three hospital sites in the southwest of England participated. Interviews were transcribed, anonymized and analysed using inductive thematicanalysis. The following two main themes with sub-themes represent the data: symptom onset to specialist care: ‘it was the blind leading the blind’ (making sense of symptoms; mis-diagnosis and missedopportunities; and fast and easy access to expertise); and diagnosis as a turning point: ‘having somebody say you’ve got something wrong with you, I was euphoric’ (validation and reassurance; weighingup treatment options; taking on self-management; and acknowledging loss and change).Conclusion. Participants were already dealing with functional limitations and were highly distressed and anxious by the time they received their diagnosis. Physical and mental outcomes could be improved by the implementation of existing psoriasis management guidelines and strategies for earlier referral from primary care to rheumatology and by the development of guidelines on educational, selfmanagement and psychological support provision soon after diagnosis

Risk assessment of failure during transitioning from in-centre to home haemodialysis

Background: Introducing a de-novo home haemodialysis (HHD) program often raises safety concerns as errors could potentially lead to serious adverse events. Despite the complexity of performing haemodialysis at home without the supervision of healthcare staff, HHD has a good safety record. We aim to pre-emptively identify and reduce the risks to our new HHD program by risk assessment and using failure mode and effects analysis (FMEA) to identify potential defects in the design and planning of HHD. Methods: We performed a general risk assessment of failure during transitioning from in-centre to HHD with a failure mode and effects analysis focused on the highest areas of failure. We collaborated with key team members from a well-established HHD program and one HHD patient. Risk assessment was conducted separately and then through video conference meetings for joint deliberation. We listed all key processes, sub-processes, step and then identified failure mode by scoring based on risk priority numbers. Solutions were then designed to eliminate and mitigate risk. Results: Transitioning to HHD was found to have the highest risk of failure with 3 main processes and 34 steps. We identified a total of 59 areas with potential failures. The median and mean risk priority number (RPN) scores from failure mode effect analysis were 5 and 38, with the highest RPN related to vascular access at 256. As many failure modes with high RPN scores were related to vascular access, we focussed on FMEA by identifying the risk mitigation strategies and possible solutions in all 9 areas in access-related medical emergencies in a bundled- approach. We discussed, the risk reduction areas of setting up HHD and how to address incidents that occurred and those not preventable. Conclusions: We developed a safety framework for a de-novo HHD program by performing FMEA in high-risk areas. The involvement of two teams with different clinical experience for HHD allowed us to successfully pre-emptively identify risks and develop solutions

Implications of the diversity of class I HLA associations in psoriatic arthritis

We sought to validate and extend the findings of a 282 psoriatic arthritis patient cohort from Dublin using a 219 patient cohort from Bath. The central finding of this study was that several structurally unrelated HLA alleles, including B*08:01:01, B*18:01:01, B*27:05:02, B*55:01:01 and C*06:02:01, were found to be significantly associated with particular phenotypic features of psoriatic arthritis, implying that the clinical diagnosis of psoriatic arthritis designates a genetically heterogeneous subset of individuals. Radiographic sacroiliitis was associated with either B*08:01:01, or B*27:05:02 with implications about the role of MHC molecules in an adaptive immune response. There are implications for psoriatic arthritis diagnostic criteria since some disease features used in the criteria are under genetic control. These findings have important implications for understanding the role of MHC alleles in directing the adaptive immune response to mediate the inflammation responsible for psoriatic arthritis

Detection of high cardiovascular risk patients with ankylosing spondylitis based on the assessment of abdominal aortic calcium as compared to carotid ultrasound

ABSTRACT: Background: This study aimed to determine whether, besides carotid ultrasound (US), a lateral lumbar spine radiography may also help identify ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. Methods: A set of 125 AS patients older than 35 years without a history of CV events, diabetes mellitus, or chronic kidney disease was recruited. Carotid US and lateral lumbar spine radiography were performed in all of them. The CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC- CORE) algorithm. Presence of carotid plaques was defined following the Mannheim Carotid Intima-media Thickness and Plaque Consensus. Abdominal aortic calcium (AAC) in a plain radiography was defined as calcific densities visible in an area parallel and anterior to the lumbar spine. Results: Carotid US showed higher sensitivity than lateral lumbar spine radiography to detect high CV risk in the 54 patients with moderate TC-SCORE (61% versus 38.9%). Using carotid plaques as the gold standard test, a predictive model that included a TC-SCORE >= 5% or the presence of AAC in the lateral lumbar spine radiography in patients with both moderate and low CV risk (< 5%) according to the TC-SCORE yielded a sensitivity of 50.9% with a specificity of 95.7% to identify high/very high CV-risk AS patients. A positive correlation between AAC and carotid plaques was observed (r2 = 0.49, p < 0.001). Conclusions: A lateral lumbar spine radiography is a useful tool to identify patients with AS at high risk of CV disease

The GOLMePsA study protocol: an investigator-initiated, double-blind, parallel-group, randomised, controlled trial of GOLimumab and methotrexate versus methotrexate in early diagnosed psoriatic arthritis using clinical and whole body MRI outcomes

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis which impacts significantly on the quality of life and work capacity of affected individuals. Recent evidence has shown that early control of inflammation in PsA leads to improved long-term outcomes. It is postulated that prompt intervention after diagnosis using a remission-induction treatment strategy will lead to improved outcomes and optimal disease control of PsA. The aim of the present study was to compare the clinical efficacy of a treatment strategy in newly diagnosed, treatment naïve PsA subjects, using the combination of golimumab (GOL), methotrexate (MTX) and steroids versus standard care (MTX monotherapy plus steroids). Methods/design: GOLMePsA is an investigator initiated, phase IIIb, single-centre, randomised, double-blind, placebo-controlled, two-armed, parallel-group, imaging-supplemented study. Eighty-eight PsA patients, diagnosed within 24 months prior to screening and treatment naïve, will be randomised at baseline to receive: (arm 1) the combination of intramuscular/intra-articular prednisolone, MTX and GOL or (arm 2) the combination of intramuscular/intra-articular prednisolone, MTX and placebo for 24 weeks (interventional period). Primary outcome measure is clinical improvement (at least 1 unit difference) in the Psoriatic ArthritiS Disease Activity Score (PASDAS) composite index. Reflecting a “step down” therapeutic approach, all participants successfully completing the interventional period will be followed up for a further 28 weeks. During this observational period, stable maintenance MTX monotherapy will continue for both arms, unless in case of intolerance or PsA relapse. In the latter case, additional treatment will be provided. Overall, the GOLMePsA study length is planned to be 52 weeks. Discussion: The hypothesis underlining this study is that very early treatment with first-line GOL reduces disease activity in PsA, in comparison to conventional therapy. Trial registration: EudraCT 2013–004122-28. 24/09/2013

Group for research and assessment of psoriasis and psoriatic arthritis:treatment recommendations for psoriatic arthritis 2015

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageTo update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA).GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire.Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema.We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) AbbVie Amgen Bristol-Myers Squibb Celgene Janssen Eli Lilly Novartis Pfizer UCB Covagen as Innovation Partner Crescendo as Innovation Partner Boehringer Ingelheim MSD Consortium of Rheumatology Researchers of North America (CORRONA) Genentech Lilly Merck Roche Almirall Biogen Idec Astellas Akros Pharma Centocor (Janssen) Beiersdorf Abbott (AbbVie) Teva Actelion Novo Nordisk Dermipsor Incyte Canfite Coronado Vertex Karyopharm CSL Behring GlaxoSmithKline XenoPort Catabasis Meiji Seika Pharma Takeda Mitsubishi Tanabe Pharma Development America Kineta Antares Medac Hospira AP Pharma Regenero

Research review: the role of cytokines in depression in adolescents: a systematic review

Background: While cytokines have been implicated in the pathophysiology of depression in adults, the potential role in younger age groups such as adolescents is less clear. This article therefore reviews the literature (a) to explore the relationship between cytokines and depression in adolescents, and (b) to examine how cytokines may be related to adolescent depression in the context of other neurobiological theories of depression. Method: A systematic review of the scientific literature on the subject was conducted in February 2013, searching the Web of Knowledge, PubMed (Medline), PsycInfo and Cochrane electronic databases. Results: Eighteen studies were identified measuring both depression or depressive symptoms and cytokines or immune markers in adolescents. Adolescents with depression show age-specific characteristics of the immune and inflammatory system, specifically in NK cell activity and in pro-inflammatory cytokines (such as IL-1 beta and TNF-alpha). In addition, the role of cytokines in adolescent depression is influenced by neurodevelopment, hormonal changes, stress and trauma. Conclusions: There may be differences in the neurobiology of adolescent major depressive disorder (MDD) compared with adult MDD. Increased understanding of the role of cytokines in adolescent MDD may lead to improved outcomes in the treatment of adolescent depression