Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Gout: HELP
Articles by Dr. Nicola Dalbeth
Based on 224 articles published since 2008
||||

Between 2008 and 2019, N. Dalbeth wrote the following 224 articles about Gout.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9
1 Guideline 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. 2012

Khanna, Dinesh / Khanna, Puja P / Fitzgerald, John D / Singh, Manjit K / Bae, Sangmee / Neogi, Tuhina / Pillinger, Michael H / Merill, Joan / Lee, Susan / Prakash, Shraddha / Kaldas, Marian / Gogia, Maneesh / Perez-Ruiz, Fernando / Taylor, Will / Lioté, Frédéric / Choi, Hyon / Singh, Jasvinder A / Dalbeth, Nicola / Kaplan, Sanford / Niyyar, Vandana / Jones, Danielle / Yarows, Steven A / Roessler, Blake / Kerr, Gail / King, Charles / Levy, Gerald / Furst, Daniel E / Edwards, N Lawrence / Mandell, Brian / Schumacher, H Ralph / Robbins, Mark / Wenger, Neil / Terkeltaub, Robert / Anonymous2310738. ·University of Michigan, Ann Arbor, MI, USA. ·Arthritis Care Res (Hoboken) · Pubmed #23024029.

ABSTRACT: -- No abstract --

2 Guideline 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. 2012

Khanna, Dinesh / Fitzgerald, John D / Khanna, Puja P / Bae, Sangmee / Singh, Manjit K / Neogi, Tuhina / Pillinger, Michael H / Merill, Joan / Lee, Susan / Prakash, Shraddha / Kaldas, Marian / Gogia, Maneesh / Perez-Ruiz, Fernando / Taylor, Will / Lioté, Frédéric / Choi, Hyon / Singh, Jasvinder A / Dalbeth, Nicola / Kaplan, Sanford / Niyyar, Vandana / Jones, Danielle / Yarows, Steven A / Roessler, Blake / Kerr, Gail / King, Charles / Levy, Gerald / Furst, Daniel E / Edwards, N Lawrence / Mandell, Brian / Schumacher, H Ralph / Robbins, Mark / Wenger, Neil / Terkeltaub, Robert / Anonymous2300738. ·University of Michigan, Ann Arbor, MI, USA. ·Arthritis Care Res (Hoboken) · Pubmed #23024028.

ABSTRACT: -- No abstract --

3 Editorial Gout in Aotearoa New Zealand: are we going to ignore this for another 3 years? 2016

Dalbeth, Nicola / Gow, Peter / Jackson, Gary / Shuker, Carl / Te Karu, Leanne / Gerard, Catherine / Winnard, Doone. ·Rheumatologist and Professor, Bone and Joint Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland. n.dalbeth@auckland.ac.nz. ·N Z Med J · Pubmed #26914294.

ABSTRACT: -- No abstract --

4 Editorial Is the double contour sign specific for gout? Or only for crystal arthritis? 2015

Singh, Jasvinder A / Dalbeth, Nicola. ·Medicine Service, Birmingham VA Medical Center, Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama, Birmingham, Alabama; and Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, USA; · University of Auckland, and Auckland District Health Board, Auckland, New Zealand. ·J Rheumatol · Pubmed #25729038.

ABSTRACT: -- No abstract --

5 Editorial Management of gout in primary care: challenges and potential solutions. 2013

Dalbeth, Nicola. · ·Rheumatology (Oxford) · Pubmed #23771950.

ABSTRACT: -- No abstract --

6 Review Combination urate-lowering therapy in the treatment of gout: What is the evidence? 2019

Perez-Ruiz, Fernando / Dalbeth, Nicola. ·Rheumatology Division, Hospital Universitario Cruces, University of the Basque Country, Bilbao 48903, Spain. Electronic address: fperezruiz@telefonica.net. · Bone and Joint Research Group, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand. ·Semin Arthritis Rheum · Pubmed #30075988.

ABSTRACT: BACKGROUND: Combination therapy that includes a uricosuric and xanthine oxidase inhibitor (XOI) is recommended in guidelines for patients with gout who do not meet treatment targets with XOI monotherapy alone. While the use of combination therapies has been investigated for many years, we reviewed data from the published studies to investigate the efficacy and safety of this approach. METHODS: Relevant published papers were identified by keyword search on PubMed and categorized according to the types of combination therapies included. Study methods and results were summarized. Outcomes of combination therapy were compared with respective monotherapies, where possible. RESULTS: Efficacy was assessed by changes in serum urate (sUA), urinary uric acid, gout flare rates, and /or tophi. Safety assessments, where reported, included adverse events and, for more recent studies, laboratory assessments. Early studies in the 1960s based on case reports or open-label designs and more recent, well-designed studies with large patient numbers provided consistent outcomes: that combination therapy with a uricosuric and a XOI provides substantially greater sUA lowering than achieved by either monotherapy. Greater sUA lowering translated to greater gout symptom control, including improved tophus resolution. CONCLUSIONS: Combination therapy with a uricosuric and an XOI offers additional sUA lowering compared to monotherapy alone and can provide benefit for achieving therapeutic targets in patients with gout who do not achieve target sUA or are intolerant of XOIs at appropriate monotherapy dosing.

7 Review What Is the Evidence for Treat-to-Target Serum Urate in Gout? 2018

Bursill, David / Dalbeth, Nicola. ·Bone and Joint Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand. · Bone and Joint Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand. n.dalbeth@auckland.ac.nz. ·Curr Rheumatol Rep · Pubmed #29516287.

ABSTRACT: PURPOSE OF REVIEW: Most current clinical guidelines for gout management advocate a treat-to-target serum urate approach, although notable differences exist. Serum urate is a rational target for gout treatment given the central role of urate in disease causality, its association with key outcomes and its practicality of use in clinical practice. This review analyses the evidence for this strategy in gout. RECENT FINDINGS: Recent studies have confirmed the efficacy of urate-lowering therapy in achieving serum urate targets, both in trials using fixed doses and those applying a treat-to-target strategy. In a limited number of long-term studies (> 12-month duration), interventions that incorporate a treat-to-target serum urate approach have been shown to promote regression of tophi, reduce the frequency of gout flares and improve MRI-detected synovitis. A strong case can be made for a treat-to-target serum urate strategy in gout, supported by existing knowledge of disease pathophysiology, outcomes from urate-lowering therapy studies and emerging results of randomised strategy trials of sufficient duration.

8 Review An association of smoking with serum urate and gout: A health paradox. 2018

Fanning, Niamh / Merriman, Tony R / Dalbeth, Nicola / Stamp, Lisa K. ·Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. Electronic address: niamh.fanning@otago.ac.nz. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. ·Semin Arthritis Rheum · Pubmed #29398126.

ABSTRACT: BACKGROUND: The potential effect of cigarette smoking on levels of serum urate and risk of gout has been considered by a large number of studies, either as the primary variable of interest or as a covariate. METHODS: Here we systematically review the published evidence relating to the relationship of smoking with serum urate, hyperuricaemia, and gout. RESULTS: Many studies have reported that smoking reduces serum urate, however, the evidence has not been conclusive with other studies pointing to the opposite or no effect. It has also been suggested that smoking reduces the risk of gout, although there is some evidence to contradict this finding. CONCLUSION: A consensus has yet to be reached as to the effect of smoking on serum urate levels and the risk of gout.

9 Review Association between ABCG2 rs2231142 and poor response to allopurinol: replication and meta-analysis. 2018

Wallace, Mary C / Roberts, Rebecca L / Nanavati, Payal / Miner, Jeffrey N / Dalbeth, Nicola / Topless, Ruth / Merriman, Tony R / Stamp, Lisa K. ·Department of Surgical Sciences, University of Otago, Dunedin, New Zealand. · Biology Department, Ardea Biosciences, Inc., San Diego, CA, USA. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. ·Rheumatology (Oxford) · Pubmed #29342288.

ABSTRACT: Objective: ABCG2 rs2231142 (Q141K) has been reported to be associated with poor response to allopurinol, while there are conflicting data on the association between the genetically independent ABCG2 rs10011796 variant and allopurinol response. The aim of this study was to replicate the association of ABCG2 rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis. Methods: Participants in the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) (n = 299) were studied. In patients with evidence of adherence to allopurinol therapy (plasma oxypurinol >20 μmol/l), good response was defined as serum urate <6 mg/dl on allopurinol ⩽300 mg/day and poor response as serum urate ⩾ 6 mg/dl despite allopurinol >300 mg/day. Association of rs2231142 and rs10011796 with poor response was tested in logistic regression models that included age, sex, BMI, ethnicity and estimated glomerular filtration rate. Results from the LASSO study and a subset of participants in the Genetics of Gout in Aotearoa New Zealand study (n = 296, including 264 from a previously published report) were combined by meta-analysis. Results: There was evidence for association of rs2231142 with allopurinol response [odds ratio (OR) = 2.35, P = 7.3 × 10-4] but not for rs10011796 (OR = 1.21, P = 0.33) in the LASSO cohort using an adjusted logistic regression model. Meta-analysis provided evidence of a significant association of rs2231142 with allopurinol response (OR = 2.43, P = 6.2 × 10-7), but not rs10011796 (OR = 1.06, P = 0.69). Conclusion: This study has confirmed the significant association of ABCG2 rs2231142 with poor response to allopurinol.

10 Review Imaging tools to measure treatment response in gout. 2018

Dalbeth, Nicola / Doyle, Anthony J. ·Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand. ·Rheumatology (Oxford) · Pubmed #29272513.

ABSTRACT: Imaging tests are in clinical use for diagnosis, assessment of disease severity and as a marker of treatment response in people with gout. Various imaging tests have differing properties for assessing the three key disease domains in gout: urate deposition (including tophus burden), joint inflammation and structural joint damage. Dual-energy CT allows measurement of urate deposition and bone damage, and ultrasonography allows assessment of all three domains. Scoring systems have been described that allow radiological quantification of disease severity and these scoring systems may play a role in assessing the response to treatment in gout. This article reviews the properties of imaging tests, describes the available scoring systems for quantification of disease severity and discusses the challenges and controversies regarding the use of imaging tools to measure treatment response in gout.

11 Review Discordant American College of Physicians and international rheumatology guidelines for gout management: consensus statement of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN). 2017

Dalbeth, Nicola / Bardin, Thomas / Doherty, Michael / Lioté, Frédéric / Richette, Pascal / Saag, Kenneth G / So, Alexander K / Stamp, Lisa K / Choi, Hyon K / Terkeltaub, Robert. ·Department of Medicine, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand. · University Paris Diderot Cité Sorbonne, Service de Rhumatologie, Centre Viggo Petersen, Lariboisière Hospital, INSERM U1132, Paris, France. · Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham (UAB), 820 Faculty Office Tower, 510 20th Street, Birmingham, Alabama 35294-3408, USA. · Service of Rheumatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Avenue Pierre Decker 4, 1011 Lausanne, Switzerland. · Department of Medicine, University of Otago, Christchurch, P.O. BOX 4345, Christchurch 8140, New Zealand. · Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit Street, Harvard Medical School, Boston, Massachusetts 02114, USA. · VA San Diego Healthcare System, 111K, 3350 La Jolla Village Drive, San Diego, California 92161, USA. ·Nat Rev Rheumatol · Pubmed #28794514.

ABSTRACT: In November 2016, the American College of Physicians (ACP) published a clinical practice guideline on the management of acute and recurrent gout. This guideline differs substantially from the latest guidelines generated by the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and 3e (Evidence, Expertise, Exchange) Initiative, despite reviewing largely the same body of evidence. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) convened an expert panel to review the methodology and conclusions of these four sets of guidelines and examine possible reasons for discordance between them. The G-CAN position, presented here, is that the fundamental pathophysiological knowledge underlying gout care, and evidence from clinical experience and clinical trials, supports a treat-to-target approach for gout aimed at lowering serum urate levels to below the saturation threshold at which monosodium urate crystals form. This practice, which is truly evidence-based and promotes the steady reduction in tissue urate crystal deposits, is promoted by the ACR, EULAR and 3e Initiative recommendations. By contrast, the ACP does not provide a clear recommendation for urate-lowering therapy (ULT) for patients with frequent, recurrent flares or those with tophi, nor does it recommend monitoring serum urate levels of patients prescribed ULT. Results from emerging clinical trials that have gout symptoms as the primary end point are expected to resolve this debate for all clinicians in the near term future.

12 Review The genetics of gout: towards personalised medicine? 2017

Dalbeth, Nicola / Stamp, Lisa K / Merriman, Tony R. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand. n.dalbeth@auckland.ac.nz. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. ·BMC Med · Pubmed #28566086.

ABSTRACT: Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.

13 Review Severe gout: Strategies and innovations for effective management. 2017

Pascual, Eliseo / Andrés, Mariano / Vázquez-Mellado, Janitzia / Dalbeth, Nicola. ·Sección de Reumatología, Hospital General Universitario de Alicante, Av. Pintor Baeza 12, 03010 Alicante, Spain; Departamento de Medicina Clínica (Reumatología), Universidad Miguel Hernández, Carretera Nacional 332 S/N, 03550, San Juan de Alicante, 03010 Alicante, Spain. Electronic address: pascual_eli@gva.es. · Sección de Reumatología, Hospital General Universitario de Alicante, Av. Pintor Baeza 12, 03010 Alicante, Spain; Departamento de Medicina Clínica (Reumatología), Universidad Miguel Hernández, Carretera Nacional 332 S/N, 03550, San Juan de Alicante, 03010 Alicante, Spain. · Servicio de Reumatología, Hospital General de México, Dr. Balmis 148, Cuauhtémoc, Doctores, 06726 Ciudad de México, D.F., Mexico. · Department of Rheumatology, Auckland District Health Board and Department of Medicine, University of Auckland, Auckland 1010, New Zealand. ·Joint Bone Spine · Pubmed #27932279.

ABSTRACT: Severe gout is characterised by frequent polyarticular flares, numerous tophi, joint damage, and musculoskeletal disability. This is a preventable condition and in many cases, represents a disease that has been insufficiently managed for years. Standard management recommendations may be insufficient for patients with severe gout; these patients frequently require intensive individualised pharmacological management with combinations of urate-lowering therapy and anti-inflammatory agents. In this article, we aim to integrate recent therapeutic advances to provide a practical framework for optimal management of severe gout.

14 Review Review: Gout: A Roadmap to Approaches for Improving Global Outcomes. 2017

Dalbeth, Nicola / Choi, Hyon K / Terkeltaub, Robert. ·University of Auckland, Auckland, New Zealand. · Massachusetts General Hospital and Harvard Medical School, Boston. · VA San Diego Healthcare System and University of California, San Diego. ·Arthritis Rheumatol · Pubmed #27389665.

ABSTRACT: -- No abstract --

15 Review Gout. 2016

Dalbeth, Nicola / Merriman, Tony R / Stamp, Lisa K. ·Department of Medicine, University of Auckland, Auckland, New Zealand. Electronic address: n.dalbeth@auckland.ac.nz. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. ·Lancet · Pubmed #27112094.

ABSTRACT: Gout is a chronic disease of deposition of monosodium urate crystals, which form in the presence of increased urate concentrations. Although environmental factors contribute to hyperuricaemia, renal and gut excretion of urate is central to regulation of serum urate, and genetic factors are important. Activation of the NLRP3 inflammasome and release of interleukin 1β have key roles in initiation of acute gout flares. A "treat to target serum urate" approach is essential for effective gout management; long-term lowering of serum urate to less than 360 μmol/L leads to crystal dissolution and ultimately to suppression of flares. An allopurinol dose-escalation strategy is frequently effective for achieving treatment targets, and several new urate-lowering drugs are also available. Worldwide, rates of initiation and continuation of urate-lowering therapy are very low, and, consequently, achievement of serum urate targets is infrequent. Strategies to improve quality of gout care are needed.

16 Review The first metatarsophalangeal joint in gout: a systematic review and meta-analysis. 2016

Stewart, Sarah / Dalbeth, Nicola / Vandal, Alain C / Rome, Keith. ·Faculty of Health and Environmental Sciences, Health & Rehabilitation Research Institute, Auckland University of Technology, Private Bag 92006, Auckland, 1142, New Zealand. sarah.stewart@aut.ac.nz. · Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. n.dalbeth@auckland.ac.nz. · Department of Biostatistics & Epidemiology, School of Public Health & Psychosocial Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Private Bag 92006, Auckland, 1142, New Zealand. alain.vandal@aut.ac.nz. · Health Intelligence & Informatics, Ko Awatea, Counties Manukau Health, Private Bag 93311, Auckland, 1640, New Zealand. alain.vandal@aut.ac.nz. · Faculty of Health and Environmental Sciences, Health & Rehabilitation Research Institute, Auckland University of Technology, Private Bag 92006, Auckland, 1142, New Zealand. keith.rome@aut.ac.nz. ·BMC Musculoskelet Disord · Pubmed #26864742.

ABSTRACT: BACKGROUND: The aim of this review was to qualitatively synthesise studies that have investigated characteristics of the first metatarsophalangeal joint (1(st) MTP) in gout and to undertake a meta-analysis to estimate the average prevalence of acute 1(st) MTP arthritis across studies in people with gout. METHODS: Studies published in English were included if they involved participants who had a diagnosis of gout and presented original findings relating to the following outcome measures associated with the 1(st) MTP: epidemiology; clinical features; structural and functional characteristics; and microscopic and imaging features. RESULTS: Forty-five studies were included in the qualitative synthesis. 1(st) MTP pain was a prominent feature in people with gout. People with 1(st) MTP gout reported walking- and general-disability. Structural and functional characteristics of 1(st) MTP gout included hallux valgus, osteoarthritis, and restricted joint motion. Successful crystal aspiration ranged from 81 to 91 % and positive crystal identification via microscopy ranged from 83 to 93 % in patients with a history of 1(st) MTP gout. Imaging features were common at the 1(st) MTP including the double contour sign, tophi and erosions. Eleven studies involving 2,325 participants were included in the meta-analysis, providing an estimate of the average prevalence of acute 1(st) MTP arthritis across studies of 73 % (95 % prediction interval 40-92 %; range 48-97 %; I(2) = 93 %). CONCLUSIONS: 1(st) MTP acute arthritis is highly prevalent in people with gout and has a substantial impact on patient-reported pain and disability. Gout affects the structure and function of the 1(st) MTP. Microscopic and imaging studies have demonstrated crystal deposition and joint damage at the 1(st) MTP in people with gout.

17 Review Imaging as a potential outcome measure in gout studies: A systematic literature review. 2016

Durcan, Laura / Grainger, Rebecca / Keen, Helen I / Taylor, William J / Dalbeth, Nicola. ·Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland; Department of Rheumatology, Johns Hopkins University School of Medicine, 1830 East Monument St, Baltimore, MD 21287. Electronic address: ldurcan1@jhmi.edu. · Department of Medicine, University of Otago, Wellington, New Zealand. · University of Western Australia, Perth, Australia. · Division of Medicine, University of Auckland, Auckland, New Zealand. ·Semin Arthritis Rheum · Pubmed #26522139.

ABSTRACT: OBJECTIVE: Despite major progress in the imaging of gout, it is unclear which domains these techniques can evaluate and whether imaging modalities have the potential to provide valid outcome measures. The aim of this study was to assess the use of imaging instruments in gout according to the Outcomes in Rheumatology Clinical Trials (OMERACT) filter to inform the development of imaging as an outcome measure. METHODS: A systematic literature search of imaging modalities for gout was undertaken. Articles were assessed by two reviewers to identify imaging domains and summarize information according to the OMERACT filter. RESULTS: The search identified 78 articles (one abstract). Modalities included were conventional radiography (CR) (16 articles), ultrasound (US) (29), conventional computed tomography (CT) (11), dual energy computed tomography (DECT) (20), and magnetic resonance imaging (MRI) (16). Three domains were identified as follows: urate deposition, joint damage, and inflammation. Although sufficient data were available to assess feasibility, validity, and reliability, comprehensive assessment of discrimination was not possible due to the paucity of prospective imaging studies. CR is widely accessible, inexpensive with a validated damage scoring system. US and MRI offer radiation-free methods of evaluating urate deposition, damage and inflammation, but may be limited by accessibility. DECT provides excellent definition of urate deposition and bone damage, but has restricted availability and requires radiation. CONCLUSIONS: Imaging methods can detect urate deposition, damage, and inflammation in gout. More than one modality may be required depending on the domains and therapeutic agent of interest. No single imaging method currently fulfils all aspects of the OMERACT filter for any domain.

18 Review Factors influencing the crystallization of monosodium urate: a systematic literature review. 2015

Chhana, Ashika / Lee, Gerald / Dalbeth, Nicola. ·Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. a.chhana@auckland.ac.nz. · Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. clee958@aucklanduni.ac.nz. · Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz. ·BMC Musculoskelet Disord · Pubmed #26467213.

ABSTRACT: BACKGROUND: Gout is a chronic disease of monosodium urate (MSU) crystal deposition. Although hyperuricaemia is the central risk factor for development of gout, not all people with hyperuricaemia have subclinical MSU crystal deposition or indeed, symptomatic disease. The aim of this systematic literature review was to identify factors that contribute to MSU crystallization. METHODS: A search was conducted of the electronic databases PubMed, Science Direct and Scopus. Articles were included if they contained original data related to MSU crystallization. The methods and results were summarized and categorized into articles describing at least one of the three key steps in MSU crystallization (reduced urate solubility, nucleation and growth). RESULTS: A total of 2175 articles were initially identified in our systematic search with 35 of these articles included in the final analysis. Elevated urate concentration was identified as a central factor driving all three stages of MSU crystallization. Factors that were found to consistently reduce urate solubility were reduced temperatures, pH 7-9 and various ions including sodium ions. Connective tissue factors including bovine cartilage homogenates and healthy human synovial fluid and serum all enhanced urate solubility. MSU nucleation was found to be increased by a number of factors, including sodium ions, uric acid binding antibodies, and synovial fluid or serum from patients with gout. Other than elevated urate concentrations, no other specific factors were identified as promoters of MSU crystal growth. CONCLUSIONS: Increased urate concentration is the key factor required at each stage of MSU crystallization. Different proteins and factors within connective tissues may promote MSU crystallization and may be important for determining the sites at which MSU crystallization occurs in the presence of elevated urate concentrations.

19 Review The gouty tophus: a review. 2015

Chhana, Ashika / Dalbeth, Nicola. ·Bone and Joint Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd. Grafton, Auckland, New Zealand, a.chhana@auckland.ac.nz. ·Curr Rheumatol Rep · Pubmed #25761926.

ABSTRACT: The tophus is the cardinal feature of advanced gout. This review summarises recent research into the biology, impact and treatment of tophaceous gout. Microscopically, tophi are chronic foreign body granuloma-like structures containing collections of monosodium urate (MSU) crystals surrounded by inflammatory cells and connective tissue. Extracellular trap formation mediated by neutrophil interactions with MSU crystals may be a central checkpoint in tophus formation. Gouty tophi impact on many aspects of health-related quality of life. Tophi are also implicated in the development of structural joint damage and increased mortality risk in people with gout. Effective treatment of tophaceous gout requires long-term urate-lowering therapy, ideally to achieve a serum urate concentration of <5 mg/dL (300 μmol/L). Recent advances in gout therapeutics have expanded urate-lowering therapy options for patients with severe tophaceous disease to allow faster regression of tophi, improved health-related quality of life and, potentially, improved structural outcomes.

20 Review Imaging as an Outcome Measure in Gout Studies: Report from the OMERACT Gout Working Group. 2015

Grainger, Rebecca / Dalbeth, Nicola / Keen, Helen / Durcan, Laura / Lawrence Edwards, N / Perez-Ruiz, Fernando / Diaz-Torne, Cesar / Singh, Jasvinder A / Khanna, Dinesh / Simon, Lee S / Taylor, William J. ·From the Department of Medicine, University of Otago Wellington, Wellington; Department of Medicine, University of Auckland, New Zealand; Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Medicine, University of Florida, Gainesville, Florida, USA; Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute, Vizcaya; Division of Rheumatology, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham, Birmingham, Alabama; Division of Rheumatology, Department of Medicine, University of Michigan, Ann Arbor, Michigan; SDG LLC, Cambridge, Massachusetts, USA.R. Grainger, PhD, FRACP, Senior Lecturer, Rheumatologist, Department of Medicine, University of Otago Wellington; N. Dalbeth, MD, FRACP, Associate Professor, Department of Medicine, University of Auckland; L. Durcan, Rheumatology Fellow, MD, Mater Misericordiae University Hospital; H. Keen, PhD, Associate Professor, School of Medicine and Pharmacology, University of Western Australia; N.L. Edwards, MD, Professor of Medicine, Department of Medicine, University of Florida; F. Perez-Ruiz, MD, Professor, Rheumatology Division, Hospital Universitario Cruces and BioCruces Health Research Institute; C. Diaz-Torne, PhD, Associate Professor and Rheumatologist; J.A. Singh, MBBS, MPH, Associate Professor of Medicine; Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham; D. Khanna, MD, MSc, Associate Professor of Medicine, Division of Rheumatology, Department of Medicine, University of Michigan; L.S. Simon, MD, Principal Advisor, SDG LLC; W.J. Taylor, PhD, FRACP, Associate Professor and Rheumatologist, Department of Medicine, University of Otago Wellington. ·J Rheumatol · Pubmed #25641895.

ABSTRACT: OBJECTIVE: The gout working group at the Outcome Measures in Rheumatology (OMERACT) 12 meeting in 2014 aimed to determine which imaging modalities show the most promise for use as measurement instruments for outcomes in studies of people with chronic gout and to identify the key foci for future research about the performance of these imaging techniques with respect to the OMERACT filter 2.0. METHODS: During the gout session, a systematic literature review of the data addressing imaging modalities including plain radiography (XR), conventional computed tomography (CT), dual-energy computed tomography (DECT), magnetic resonance imaging (MRI), and ultrasound (US) and the fulfillment of the OMERACT filter 2.0 was presented. RESULTS: The working group identified 3 relevant domains for imaging in gout studies: urate deposition (tophus burden), joint inflammation, and structural joint damage. CONCLUSION: The working group prioritized gaps in the data and identified a research agenda.

21 Review Advances in pharmacotherapy for the treatment of gout. 2015

Robinson, Philip C / Dalbeth, Nicola. ·University of Queensland, Queensland Brain Institute, Centre for Neurogenetics and Statistical Genomics , Queensland , Australia. ·Expert Opin Pharmacother · Pubmed #25547991.

ABSTRACT: INTRODUCTION: Gout is a common inflammatory arthritis affecting almost 6% of US males and 2% of US females. The central cause of gout is deposition of monosodium urate crystals, and the focus of treatment is aimed at crystal dissolution using urate-lowering therapy. AREAS COVERED: The review describes the current treatments for urate-lowering therapy including allopurinol, febuxostat, probenecid, benzbromarone and pegloticase. Anti-inflammatory treatment of acute flares and prophylaxis of flares with NSAIDs, colchicine, corticosteroids and anti-IL-1 agents is also reviewed. In addition, drugs in Phase III clinical trials for gout indications are reviewed. EXPERT OPINION: In the last decade, there has been major progress in the pharmacotherapy of gout. Management guidelines have emphasized the importance of a therapeutic serum urate target for effective gout management. Studies have identified the safe and effective dosing strategies for 'old' drugs such as allopurinol and colchicine. New therapeutic agents have been developed and approved for both urate-lowering therapy and anti-inflammatory treatment of acute flares. However, quality of care remains a major challenge in gout management, and strategies to ensure best practice require further focus to ensure that the progress of the last decade translates into clinical benefit for people with gout.

22 Review A review of uric acid, crystal deposition disease, and gout. 2015

Perez-Ruiz, Fernando / Dalbeth, Nicola / Bardin, Tomas. ·Servicio de Reumatologia, Hospital Universitario Cruces, and BioCruces Health Research Institute, 48903, Baracaldo, Vizcaya, Spain, fernando.perezruiz@osakidetza.net. ·Adv Ther · Pubmed #25533440.

ABSTRACT: There has been increased interest in gout in both academic and clinical practice settings. Several reasons may explain this. The prevalence of both hyperuricemia and gout has risen in the last decades in developed countries and therefore the burden of gout has increased. The association of hyperuricemia and gout with cardiovascular outcomes and the opportunity of further benefits of intervention on hyperuricemia have been recently highlighted in the literature. Imaging techniques have proven to be useful for detection of urate deposition, even prior to the first clinical symptoms, enabling the evaluation of the extent of deposition and providing objective measurement of crystal depletion during urate-lowering treatment. Treating to target is increasingly used as the approach to treatment of diverse diseases. Therefore, different targets have been recommended for different stages of the burden of disease and for different stages of treatment. The final strategic target, to which any effort should be taken into consideration, is to completely dissolve urate crystals in tissues and therefore avoid further symptoms and structural damage of involved musculoskeletal structures. In summary, evidence suggest that an early approach to the treatment of gout and associated comorbidities is advisable, that new imaging techniques may help to evaluate both the burden of deposition and response to urate-lowering treatment in selected patients, and finally that the final strategic objective of healthcare for patients with gout is to completely resolve urate crystal deposits.

23 Review Imaging modalities for the classification of gout: systematic literature review and meta-analysis. 2015

Ogdie, Alexis / Taylor, William J / Weatherall, Mark / Fransen, Jaap / Jansen, Tim L / Neogi, Tuhina / Schumacher, H Ralph / Dalbeth, Nicola. ·Division of Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Medicine, University of Otago, Wellington, New Zealand. · Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. · Sections of Epidemiology and Rheumatology, Boston University School of Medicine, Boston, Massachusetts, USA. · Department of Medicine, University of Auckland, Auckland, New Zealand. ·Ann Rheum Dis · Pubmed #24915980.

ABSTRACT: BACKGROUND: Although there has been major progress in gout imaging, no gout classification criteria currently include advanced imaging techniques. OBJECTIVE: To examine the usefulness of imaging modalities in the classification of gout when compared to monosodium urate (MSU) crystal confirmation as the gold standard, in order to inform development of new gout classification criteria. METHODS: We systematically reviewed the published literature concerning the diagnostic performance of plain film radiography, MRI, ultrasound (US), conventional CT and dual energy CT (DECT). Only studies with MSU crystal confirmation as the gold standard were included. When more than one study examined the same imaging feature, the data were pooled and summary test characteristics were calculated. RESULTS: 11 studies (9 manuscripts and 2 meeting abstracts) satisfied the inclusion criteria. All were set in secondary care, with mean gout disease duration of at least 7 years. Three features were examined in more than one study: the double contour sign (DCS) on US, tophus on US, and MSU crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus, were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively. CONCLUSIONS: US and DECT show promise for gout classification but the few studies to date have mostly been in patients with longstanding, established disease. The contribution of imaging over clinical features for gout classification criteria requires further examination.

24 Review Sugar-sweetened beverages, urate, gout and genetic interaction. 2014

Merriman, T R / Dalbeth, N / Johnson, R J. · ·Pac Health Dialog · Pubmed #25928993.

ABSTRACT: The clinical manifestations of gout occur as a result of immune responses to monosodium urate crystals. Elevated serum levels of urate (hyperuricemia) are a prerequisite for the development of gout with reduced fractional renal excretion of uric acid (FEUA) an important cause. In New Zealand, Mãori and Pacific Island people have inherently raised urate levels with one consequence a higher prevalence of more severe gout. One characteristic metabolic effect of fructose, present in sugar-sweetened beverages (SSB), is raised urate from hepatic processing of fructose. Here we discuss, and place in a biological context evidence, linking consumption of SSB with hyperuricemia and gout, including the first review of recent ecological and clinical studies of the impact of fructose and SSB exposure in Pacific Island people. Both increased serum urate and increased FEUA are observed in clinical studies examining the effects of an acute fructose load. In contrast, chronic exposure to increased fructose in the diet also leads to increased serum urate concentrations, but reduced FEUA. Epidemiological studies have consistently associated SSB consumption with increased serum urate levels and increased risk of gout. Non-additive interaction of SSB consumption with a genetic variant of a uric acid transporter in serum urate levels and gout risk emphasizes the causality of SSB in gout. Taken together these data demonstrate the hyperuricemic effect of SSB and fructose, with biochemical pathways reasonably well understood. The evidence that dietary fructose increases urate is strong. The evidence summarized here is of sufficient weight to recommend reduction of SSB consumption, particularly in Pacific Island and Mãori people, to reduce the burden of gout.

25 Review Mechanism of action of colchicine in the treatment of gout. 2014

Dalbeth, Nicola / Lauterio, Thomas J / Wolfe, Henry R. ·Department of Medicine, University of Auckland, Auckland, New Zealand. Electronic address: n.dalbeth@auckland.ac.nz. · Medical Affairs, URL Pharma Inc, Philadelphia, Pennsylvania. · Kyowa Kirin Pharma, Inc, New Jersey. ·Clin Ther · Pubmed #25151572.

ABSTRACT: PURPOSE: The aims of this article were to systematically review the literature about the mechanism of action of colchicine in the multimodal pathology of acute inflammation associated with gout and to consider the clinical utility of colchicine in other chronic inflammatory diseases. METHODS: The English-language literature on PubMed was searched for articles published between 1990 and October 2013, with a cross-reference to citations across all years. Relevant articles pertaining to the mechanism of action of colchicine and the clinical applications of colchicine in gout and other inflammatory conditions were identified and reviewed. FINDINGS: The molecular pathology of acute inflammation associated with gouty arthritis involves several concurrent pathways triggered by a variety of interactions between monosodium urate crystals and the surface of cells. Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Many of these cellular processes can be found in other diseases involving chronic inflammation. The multimodal mechanism of action of colchicine suggests potential efficacy of colchicine in other comorbid conditions associated with gout, such as osteoarthritis and cardiovascular disease. IMPLICATIONS: Colchicine has multiple mechanisms of action that affect inflammatory processes and result in its utility for treating and preventing acute gout flare. Other chronic inflammatory diseases that invoke these molecular pathways may represent new therapeutic applications for colchicine.

Next