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PURPOSE: Juvenile xanthogranuloma (JXG) is a subtype of histiocytosis characterised histologically by foamy non-Langerhan cells with Touton giant cells. It typically manifests as a single self-limiting cutaneous nodule in the paediatric population. Orbital JXG is extremely rare, and its clinical course and management are not well understood or defined. Herein we present 3 cases of orbital JXG and provide a detailed literature review. METHODS: Review of 3 cases with orbital JXG and literature review of all published cases. RESULTS: Three presented cases demonstrate the heterogeneous clinical course of orbital JXG. Although centred around the use of steroids, there is neither robust evidence nor consensus on its management. The wider JXG literature is currently concentrated around the classification of JXG with respect to histiocytosis, especially the exclusion of extracutaneous JXG as separate diseases. This separation is based on clinical, histopathological, and molecular findings. It is unclear where orbital JXG best fits in this emerging classification of JXG. CONCLUSION: Our review of the cases and literature on orbital JXG show that it may manifest with variable clinical course and its molecular pathogenic mechanism may be different to that of the cutaneous JXG.
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Background: There is emerging evidence which suggests the utility of artificial intelligence (AI) in the diagnostic assessment and pre-treatment evaluation of thyroid eye disease (TED). This scoping review aims to (1) identify the extent of the available evidence (2) provide an in-depth analysis of AI research methodology of the studies included in the review (3) Identify knowledge gaps pertaining to research in this area. Methods: This review was performed according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). We quantify the diagnostic accuracy of AI models in the field of TED assessment and appraise the quality of these studies using the modified QUADAS-2 tool. Results: A total of 13 studies were included in this review. The most common AI models used in these studies are convolutional neural networks (CNN). The majority of the studies compared algorithm performance against healthcare professionals. The overall risk of bias and applicability using the modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool led to most of the studies being classified as low risk, although higher deficiency was noted in the risk of bias in flow and timing. Conclusions: While the results of the review showed high diagnostic accuracy of the AI models in identifying features of TED relevant to disease assessment, deficiencies in study design causing study bias and compromising study applicability were noted. Moving forward, limitations and challenges inherent to machine learning should be addressed with improved standardized guidance around study design, reporting, and legislative framework.
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Inteligencia Artificial , Oftalmopatía de Graves , Humanos , Algoritmos , Oftalmopatía de Graves/diagnóstico , Aprendizaje Automático , Redes Neurales de la ComputaciónRESUMEN
Eosinophilic angiocentric fibrosis (EAF) has been postulated to lie on the spectrum of IgG4-related disease (IgG4-RD) in a study reported in 2011. However, the aetiology of EAF remains controversial, despite increasing literature reporting IgG4-RD targeted investigations in those studies. This review aims to formally evaluate the relationship between EAF and IgG4-RD using the latest 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification scheme for IgG4-RD. A literature search was performed on the PubMed database for all studies describing patients diagnosed with EAF. Additionally, two EAF cases were retrospectively identified from our institution and presented. The demographics, clinical presentation, histological and serological data of each patient were analysed. A total of 20 cases were evaluated, including 18 patients from 14 articles in the English literature and two cases from our institution. Six of 20 (30%) patients with EAF met the criteria for IgG4-RD with the 2019 ACR/EULAR classification scheme. This represents the first attempt at formally evaluating the relationship between EAF and IgG4-RD using a validated set of classification criteria. Using the currently available data, a small proportion of patients with EAF met the criteria for IgG4-RD. However, various limitations of this study suggest that further efforts at disease characterization of EAF may be required.
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Enfermedad Relacionada con Inmunoglobulina G4 , Fibrosis , Humanos , Inmunoglobulina G , Enfermedad Relacionada con Inmunoglobulina G4/patología , Estudios Retrospectivos , Estados UnidosRESUMEN
PURPOSE: To compare the surgical outcomes of unilateral lateral rectus recession to bilateral lateral rectus recession for small angle intermittent exotropia. METHODS: This was a retrospective cohort study of pediatric patients with an intermittent exotropia between 16 and 20 prism diopters (PD) who underwent unilateral lateral rectus recession or bilateral lateral rectus recession at a single tertiary care pediatric hospital. The primary outcome was success (exotropia < 10 PD of esotropia < 5 PD, no decrease in stereopsis > 0.6 log arcsec, and no reoperation) at 12 months postoperatively. Secondary outcomes included survival analysis of time to surgical failure, surgical dose-response, and improvement in central fusion or stereopsis. RESULTS: At 12 months, successful outcomes were achieved in 13 of 27 patients (46%) in the bilateral lateral rectus recession group and 19 of 28 patients (70%) in the unilateral lateral rectus recession group, which was not a statistically significant difference (P = .10). Survival analysis showed a trend toward a higher rate of failure in the bilateral lateral rectus recession group compared to the unilateral lateral rectus recession group (P = .04). The mean surgical dose-response was 1.7 PD/mm at 1 week and 1.0 PD/mm at 12 months for the bilateral lateral rectus recession group, and 2.0 PD/mm at 1 week postoperatively and 1.4 PD/mm at 12 months postoperatively for the unilateral lateral rectus recession group. There were no cases of long-term postoperative lateral incomitance in either group. CONCLUSIONS: Unilateral lateral rectus recession and bilateral lateral rectus recession have similar success rates for small angle intermittent exotropia after at least 12 months of follow-up. Randomized controlled trials in surgical management of intermittent exotropia should consider unilateral lateral rectus recession as a treatment arm. [J Pediatr Ophthalmol Strabismus. 2022;59(5):350-355.].
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Exotropía , Niño , Enfermedad Crónica , Exotropía/cirugía , Estudios de Seguimiento , Humanos , Músculos Oculomotores/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Estudios Retrospectivos , Resultado del Tratamiento , Visión Binocular/fisiologíaRESUMEN
The Taiwan Photon Source (TPS) with high brightness and energy tunability is suitable for applications in spectroscopy. The tender X-ray absorption beamline will be optimized for X-ray absorption spectroscopy measurements using a bending-magnet source in a unique photon energy range (1.7-10â keV) and two crystal pairs [InSb(111) and Si(111)] separated using back-to-back double-crystal monochromators (DCMs). InSb crystals are typically used in the lower photon energy range of 1.7-3.5â keV. However, the poor thermal conductivity of InSb crystals leads to severe deformation. This factor should be considered when the monochromator is installed on a tender X-ray beamline in a storage ring with a high power density. There are many approaches to reducing the thermal load on the first crystal of a DCM. Double-bounce high harmonics rejection mirrors in front of the DCM serve not only to reduce the high-order harmonics but also to absorb considerable quantities of heat. Two coating stripes on the silicon surfaces with a variable incident angle will be key to solving the thermal load on this beamline.
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Celulitis Orbitaria , Enfermedades Orbitales , Absceso/diagnóstico , Absceso/tratamiento farmacológico , Absceso/etiología , Antibacterianos/uso terapéutico , Capnocytophaga , Niño , Humanos , Celulitis Orbitaria/diagnóstico , Celulitis Orbitaria/tratamiento farmacológico , Celulitis Orbitaria/etiología , Enfermedades Orbitales/complicaciones , Enfermedades Orbitales/diagnósticoRESUMEN
The vast majority of marketed drugs are orally administrated. As such, drug absorption is one of the important drug metabolism and pharmacokinetics parameters that should be assessed in the process of drug discovery and development. A nonlinear quantitative structure-activity relationship (QSAR) model was constructed in this investigation using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to render the extremely complicated relationships between descriptors and intestinal permeability that can take place through various passive diffusion and carrier-mediated active transport routes. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 53, r2 = 0.93, q CV 2 = 0.84, RMSE = 0.17, s = 0.08), test set (n = 13, q2 = 0.75-0.89, RMSE = 0.26, s = 0.14), and even outlier set (n = 8, q2 = 0.78-0.92, RMSE = 0.19, s = 0.09). The built HSVR model consistently met the most stringent criteria when subjected to various statistical assessments. A mock test also assured the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.
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Simulación por Computador , Intestinos/fisiología , Máquina de Vectores de Soporte , Animales , Humanos , Permeabilidad , Ratas , Análisis de Regresión , Reproducibilidad de los ResultadosRESUMEN
Oral administration is the preferred and predominant route of choice for medication. As such, drug absorption is one of critical drug metabolism and pharmacokinetics (DM/PK) parameters that should be taken into consideration in the process of drug discovery and development. The cell-free in vitro parallel artificial membrane permeability assay (PAMPA) has been adopted as the primary screening to assess the passive diffusion of compounds in the practical applications. A classical quantitative structure-activity relationship (QSAR) model and a machine learning (ML)-based QSAR model were derived using the partial least square (PLS) scheme and hierarchical support vector regression (HSVR) scheme to elucidate the underlying passive diffusion mechanism and to predict the PAMPA effective permeability, respectively, in this study. It was observed that HSVR executed better than PLS as manifested by the predictions of the samples in the training set, test set, and outlier set as well as various statistical assessments. When applied to the mock test, which was designated to mimic real challenges, HSVR also showed better predictive performance. PLS, conversely, cannot cover some mechanistically interpretable relationships between descriptors and permeability. Accordingly, the synergy of predictive HSVR and interpretable PLS models can be greatly useful in facilitating drug discovery and development by predicting passive diffusion.
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Absorción Fisiológica , Permeabilidad de la Membrana Celular , Simulación por Computador , Relación Estructura-Actividad Cuantitativa , Descubrimiento de Drogas/métodos , Humanos , Aprendizaje AutomáticoRESUMEN
IMPORTANCE: There is limited literature on oral statin use and its association with dry eye. BACKGROUND: To analyse the association between dyslipidaemia, use of oral statin drugs, and symptoms of dry eye disease (DED) among older adults. DESIGN: Population-based study. PARTICIPANTS: Participants of the Blue Mountains Eye Study III (BMESIII), a large cohort study in suburban Sydney, aged 60 years or older (mean age = 74, range = 60-97, n = 1680) were analysed. METHODS: Information on DED symptoms and statin use were obtained from an interviewer-administered questionnaire. Serum lipid profiles were determined from fasting blood tests. MAIN OUTCOME MEASURES: The association of various DED symptoms, as well as their number and their severity, with dyslipidaemia and oral statin intake was evaluated. RESULTS: At least one DED symptom was reported in 52% (n = 1029) of the population. Patients with hypercholesterolaemia (>5.5 mmol/L) did not report more DED symptoms than those without hypercholesterolaemia. Neither serum high-density lipoprotein nor low-density lipoprotein levels were associated with any DED symptoms. Patients taking oral statins were more likely to report one or more moderate to severe symptoms of DED (odds ratio: 2.054, 95% confidence interval: 1.281-3.295). CONCLUSIONS AND RELEVANCE: The association between oral statin use and presence of moderate to severe DED symptomatology is a novel finding that deserves further mechanistic and clinical correlation in order to determine its potential, or lack thereof, for the management of dry eye.
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Síndromes de Ojo Seco/inducido químicamente , Dislipidemias/inducido químicamente , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Administración Oral , Anciano , Anciano de 80 o más Años , Estudios Transversales , Síndromes de Ojo Seco/diagnóstico , Dislipidemias/diagnóstico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Lípidos/sangre , Masculino , Persona de Mediana Edad , Nueva Gales del Sur/epidemiología , Oportunidad Relativa , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or bloodâ»brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structureâ»activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, qCV2 = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80â»0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/química , Simulación por Computador , Modelos Moleculares , Máquina de Vectores de Soporte , Humanos , Relación Estructura-Actividad CuantitativaRESUMEN
One recognized complication of trabeculectomy with visually devastating potential is blebitis. We present a case of a 74-year-old woman with a culture and polymerase chain reaction-positive Abiotrophia defectiva bleb-associated endophthalmitis. Abiotrophia defectiva is a rare but possible cause of endophthalmitis secondary to blebitis and should be considered in culture-negative cases. Prompt identification, hence directed eradication, of the causative organism in such visually threatening cases may be facilitated by requesting polymerase chain reaction and 16S ribosomal RNA sequencing.
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Endoftalmitis/microbiología , Infecciones Bacterianas del Ojo/microbiología , Infecciones por Bacterias Grampositivas/microbiología , Estructuras Creadas Quirúrgicamente/microbiología , Abiotrophia , Anciano , Antibacterianos/uso terapéutico , Atropina/administración & dosificación , Ceftazidima/uso terapéutico , Cefalotina/administración & dosificación , Quimioterapia Combinada , Endoftalmitis/diagnóstico , Endoftalmitis/tratamiento farmacológico , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Femenino , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , Implantación de Lentes Intraoculares , Midriáticos/administración & dosificación , Facoemulsificación , Reacción en Cadena de la Polimerasa , ARN Bacteriano/genética , ARN Ribosómico 16S , Trabeculectomía , Vancomicina/uso terapéutico , Cuerpo Vítreo/microbiologíaRESUMEN
OBJECTIVE: Allopurinol, an antihyperuricaemic agent, is one of the common causes of life-threatening severe cutaneous adverse reactions (SCAR), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The prognostic factors for allopurinol-related SCAR remain unclear. This study aimed to investigate the relationship of dosing, renal function, plasma levels of oxypurinol and granulysin (a cytotoxic protein of SJS/TEN), the disease severity and mortality in allopurinol-SCAR. METHODS: We prospectively enrolled 48 patients with allopurinol-SCAR (26 SJS/TEN and 22 DRESS) and 138 allopurinol-tolerant controls from 2007 to 2012. The human leucocyte antigen (HLA)-B*58:01 status, plasma concentrations of oxypurinol and granulysin were determined. RESULTS: In this cohort, HLA-B*58:01 was strongly associated with allopurinol-SCAR (p<0.001, OR (95% CI) 109 (25 to 481)); however, the initial/maintenance dosages showed no relationship with the disease. Poor renal function was significantly associated with the delayed clearance of plasma oxypurinol, and increased the risk of allopurinol-SCAR (p<0.001, OR (95% CI) 8.0 (3.9 to 17)). Sustained high levels of oxypurinol after allopurinol withdrawal correlated with the poor prognosis of allopurinol-SCAR. In particular, the increased plasma levels of oxypurinol and granulysin linked to the high mortality of allopurinol-SJS/TEN (p<0.01), and strongly associated with prolonged cutaneous reactions in allopurinol-DRESS (p<0.05). CONCLUSIONS: Impaired renal function and increased plasma levels of oxypurinol and granulysin correlated with the poor prognosis of allopurinol-SCAR. Allopurinol prescription is suggested to be avoided in subjects with renal insufficiency and HLA-B*58:01 carriers. An early intervention to increase the clearance of plasma oxypurinol may improve the prognosis of allopurinol-SCAR.
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Alopurinol/efectos adversos , Antígenos de Diferenciación de Linfocitos T/sangre , Erupciones por Medicamentos/etiología , Antígenos HLA-B/inmunología , Oxipurinol/sangre , Insuficiencia Renal/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Erupciones por Medicamentos/sangre , Erupciones por Medicamentos/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Insuficiencia Renal/sangre , Insuficiencia Renal/mortalidad , Tasa de Supervivencia/tendencias , Taiwán/epidemiología , Adulto JovenAsunto(s)
Alopurinol/efectos adversos , Pueblo Asiatico/genética , Antígenos HLA-B/genética , Síndrome de Stevens-Johnson/etiología , Alopurinol/uso terapéutico , Artritis Gotosa/tratamiento farmacológico , Pruebas Genéticas , Humanos , Riesgo , Síndrome de Stevens-Johnson/inducido químicamente , Síndrome de Stevens-Johnson/genéticaRESUMEN
BACKGROUND: Recurrent corneal erosion is a common cause of disabling ocular symptoms and predisposes the cornea to infection. It may follow corneal trauma. Measures to prevent the development of recurrent corneal erosion following corneal trauma have not been firmly established. Once recurrent corneal erosion develops simple medical therapy (standard treatment) may lead to resolution of the episode. However, some patients continue to suffer when such therapy fails and once resolved further episodes of recurrent erosion may occur. A number of treatment and prophylactic options are then available but there is no agreement as to the best option. OBJECTIVES: To assess the effectiveness and safety of prophylactic and treatment regimens for recurrent corneal erosion. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to June 2012), EMBASE (January 1980 to June 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2012. We also contacted researchers in the field. SELECTION CRITERIA: We included randomised and quasi-randomised trials that compared a prophylactic or treatment regimen with another prophylaxis/treatment or no prophylaxis/treatment for patients with recurrent corneal erosion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. We contacted study authors for additional information. MAIN RESULTS: Seven randomised and one quasi-randomised controlled trial were included in the review. The trials were heterogenous and of poor quality. Safety data presented were incomplete. For the treatment of recurrent corneal erosion, a single-centre trial in the UK with 30 participants showed that oral tetracycline 250 mg twice daily for 12 weeks or topical prednisolone 0.5% four times daily for one week, or both, in addition to standard treatment, accelerated healing rates and improved symptoms. A single-centre trial in Sweden with 56 participants showed that excimer laser ablation in addition to mechanical debridement may reduce the number of erosions and improve symptoms. Furthermore, in a single-centre trial in Germany with 100 participants, transepithelial technique for excimer laser ablation had the same efficacy as the traditional subepithelial excimer laser technique but caused less pain. In a small study of 24 participants in UK, therapeutic contact lens wear was inferior to lubricant drops and ointment in abolishing the symptoms of recurrent corneal erosion and had a high complication rate, although the contact lenses used were the older generation with low oxygen permeability. A recent study in Hong Kong with 48 participants found diamond burr polishing to reduce episodes of recurrent corneal erosion. For prophylaxis of further episodes of recurrent corneal erosion, there was no difference in the occurrence of objective signs of recurrent erosion between hypertonic saline ointment versus tetracycline ointment or lubricating ointment in a small Japanese study with 26 participants. Also, in a single-centre study in the UK with 117 participants, there was no difference in symptom improvement between hypertonic saline versus paraffin ointment when used for prophylaxis. In a UK study with 42 participants, lubricating ointment at night in addition to standard treatment to prevent recurrence following traumatic corneal abrasion (erosion) caused by fingernail injury led to increased symptoms of recurrent corneal erosion compared to standard therapy alone. AUTHORS' CONCLUSIONS: Well-designed, masked, randomised controlled trials using standardised methods are needed to establish the benefits of new and existing prophylactic and treatment regimes for recurrent corneal erosion. International consensus is also needed to progress research efforts towards evaluation of the major effective treatments for recurrent corneal erosions.
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Enfermedades de la Córnea/prevención & control , Lesiones de la Cornea , Infecciones del Ojo/prevención & control , Antibacterianos/uso terapéutico , Lentes de Contacto , Enfermedades de la Córnea/terapia , Desbridamiento/métodos , Infecciones del Ojo/etiología , Glucocorticoides/uso terapéutico , Humanos , Prednisolona/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención Secundaria , Tetraciclina/uso terapéuticoRESUMEN
Benzbromarone, a potent uricosuric drug, was introduced in the 1970s and was viewed as having few associated serious adverse reactions. It was registered in about 20 countries throughout Asia, South America and Europe. In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies. The withdrawal has greatly limited its availability around the world, and increased difficulty in accessing it in other countries where it has never been available.The overall aim of this paper is to determine if the withdrawal of benzbromarone was in the best interests of gouty patients and to present a benefit-risk assessment of benzbromarone. To determine this, we examined (i) the clinical benefits associated with benzbromarone treatment and compared them with the success of alternative therapies such as allopurinol and probenecid, particularly in patients with renal impairment; (ii) the attribution of the reported cases of hepatotoxicity to treatment with benzbromarone; (iii) the incidence of hepatotoxicity possibly due to benzbromarone; (iv) adverse reactions to allopurinol and probenecid. From these analyses, we present recommendations on the use of benzbromarone.Large reductions in plasma urate concentrations in patients with hyperuricaemia are achieved with benzbromarone and most patients normalize their plasma urate. The half-life of benzbromarone is generally short (about 3 hours); however, a uricosuric metabolite, 6-hydroxybenzbromarone, has a much longer half-life (up to 30 hours) and is the major species responsible for the uricosuric activity of benzbromarone, although its metabolism by cytochrome P450 (CYP) 2C9 in the liver may vary between patients as a result of polymorphisms in this enzyme. It is effective in patients with moderate renal impairment. Standard dosages of benzbromarone (100 mg/day) tend to produce greater hypouricaemic effects than standard doses of allopourinol (300 mg/day) or probenecid (1000 mg/day).Adverse effects associated with benzbromarone are relatively infrequent, but potentially severe. Four cases of benzbromarone-induced hepatotoxicity were identified from the literature. Eleven cases have been reported by Sanofi-Synthélabo, but details are not available in the public domain. Only one of the four published cases demonstrated a clear relationship between the drug and liver injury as demonstrated by rechallenge. The other three cases lacked incontrovertible evidence to support a diagnosis of benzbromarone-induced hepatotoxicity. If all the reported cases are assumed to be due to benzbromarone, the estimated risk of hepatotoxicity in Europe was approximately 1 in 17 000 patients but may be higher in Japan.Benzbromarone is also an inhibitor of CYP2C9 and so may be involved in drug interactions with drugs dependent on this enzyme for clearance, such as warfarin. Alternative drugs to benzbromarone have significant adverse reactions. Allopurinol is associated with rare life-threatening hypersensitivity syndromes; the risk of these reactions is approximately 1 in 56 000. Rash occurs in approximately 2% of patients taking allopurinol and usually leads to cessation of prescription of the drug. Probenecid has also been associated with life-threatening reactions in a very small number of case reports, but it frequently interacts with many renally excreted drugs. Febuxostat is a new xanthine oxidoreductase inhibitor, which is still in clinical trials, but abnormal liver function is the most commonly reported adverse reaction.Even assuming a causal relationship between benzbromarone and hepatotoxicity in the identified cases, benefit-risk assessment based on total exposure to the drug does not support the decision by the drug company to withdraw benzbromarone from the market given the paucity of alternative options. It is likely that the risks of hepatotoxicity could be ameliorated by employing a graded dosage increase, together with regular monitoring of liver function. Determination of CYP2C9 status and consideration of potential interactions through inhibition of this enzyme should be considered. The case for wider and easier availability of benzbromarone for treating selected cases of gout is compelling, particularly for patients in whom allopurinol produces insufficient response or toxicity.We conclude that the withdrawal of benzbromarone was not in the best interest of patients with gout.