Esophageal atresia and tracheoesophageal fistula associated with tetralogy of Fallot: a review of mortality.

INTRODUCTION: Oesophageal atresia ± tracheoesophageal fistula (EA/TEF) associated with congenital heart disease (CHD) carries a worse prognosis than EA/TEF alone. Though the Spitz classification takes major CHD into account, there are no data regarding survival with the specific combination of EA/TEF and Tetralogy of Fallot (TOF). With advances in postnatal care, we hypothesised that, survival is improving in these complex patients. This study reports morbidity and mortality outcomes of newborns with oesophageal atresia and TOF cardiac malformations METHODS: All patients with EA/TEF and TOF treated at Alder Hey Children's Hospital between the years 2000-2020, were identified. Data sets regarding gestation, birth weight, associated anomalies, operative intervention, morbidity, and mortality were analysed. RESULTS: Of a total of 350, EA/TEF patients 9 (2.6%) cases had EA/TEF associated with TOF (M:F 4:5). The median gestational age was 35/40 (range 28-41 weeks) with a median birth weight of 1790 g (range 1060-3350 g). Overall survival was 56% (5/9 cases) and all survivors remain under follow up (range 37-4458 days). Surgical strategies for managing EA/TEF with Fallot's tetralogy included 6/9 primary repairs and 3/9 cases with TEF ligation only (+ gastrostomy ± oesophagostomy). CONCLUSIONS: This study reports outcome data from one of the largest series of EA TEF patients with Fallot's tetralogy. Whilst outcomes may be challenging for this unique patient cohort, survival metrics provide important prognostic information that can be widely shared with health care teams and parents.

Diagnostic accuracy of midtrimester antenatal ultrasound for multicystic dysplastic kidneys.

OBJECTIVES: To establish the diagnostic accuracy of obstetric ultrasound at a tertiary fetal medicine center in the prenatal detection of unilateral and bilateral multicystic dysplastic kidney (MCDK) in fetuses in which this condition was suspected, and to undertake a systematic review of the relevant literature. METHODS: This was a retrospective observational study of all cases referred to a regional tertiary fetal medicine unit due to suspicion of either unilateral or bilateral MCDK between 1997 and 2015. Diagnosis was confirmed by postnatal ultrasound reports or postmortem examination. The accuracy of prenatal ultrasound in the diagnosis of MCDK was calculated. Using a systematic search strategy we also performed a review of the literature regarding the prenatal diagnosis and diagnostic accuracy of MCDK. RESULTS: We included 144 women in our analysis; 37 (25.7%) opted for pregnancy termination (TOP) (due to unilateral MCDK with additional abnormalities, suspected bilateral MCDK or severe obstructive uropathy). Complete pre- and postnatal data were available in 126 pregnancies, including 104 livebirths, 19 TOPs with postmortem findings available and three intrauterine fetal deaths. Two infants died shortly after birth (due to known bilateral MCDK or known cranial vault defect). The overall number of cases of MCDK confirmed postnatally was 100; of these, 98 were diagnosed prenatally (true positive), while two were thought to be hydronephrosis prenatally (false negative) and the diagnosis of MCDK was made after birth. In nine cases, the initial antenatal diagnosis of suspected MCDK was revised, either later in pregnancy (n = 2) or postnatally (n = 7) (false positive). Overall, the diagnostic accuracy in our population for the use of antenatal ultrasound to detect MCDK was 91.3%, while that reported in the existing literature was found to range from 53.3% to 100%. MCDK was isolated in the majority (71%) of cases, while in 29% of cases it was found to be associated with other renal and extrarenal fetal abnormalities. CONCLUSIONS: Antenatal ultrasound had a diagnostic accuracy of about 91% in the prediction of postnatal MCDK and can therefore be used to guide antenatal counseling. However, prenatal or postnatal revision of the diagnosis occurred in about 7% of cases and parents should be counseled appropriately. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Body size in relation to incidence of subtypes of haematological malignancy in the prospective Million Women Study.

BACKGROUND: Greater adiposity and height have been associated with increased risk of haematological malignancies. Associations for disease subtypes are uncertain. METHODS: A cohort of 1.3 million middle-aged U.K. women was recruited in 1996-2001 and followed for 10 years on average. Potential risk factors were assessed by questionnaire. Death, emigration, and incident cancer were ascertained by linkage to national registers. Adjusted relative risks were estimated by Cox regression. RESULTS: During follow-up, 9162 participants were diagnosed with lymphatic or haematopoietic cancers. Each 10 kg m(-2) increase in body mass index was associated with relative risk of 1.20 (95% confidence interval: 1.13-1.28) for lymphoid and 1.37 (1.22-1.53) for myeloid malignancy (P=0.06 for heterogeneity); similarly, Hodgkin lymphoma 1.64 (1.21-2.21), diffuse large B-cell lymphoma 1.36 (1.17-1.58), plasma cell neoplasms 1.21 (1.06-1.39), acute myeloid leukaemia 1.47 (1.19-1.81), and myeloproliferative/myelodysplastic syndromes 1.32 (1.15-1.52). Each 10 cm increase in height was associated with relative risk of 1.21 (1.16-1.27) for lymphoid and 1.11 (1.02-1.21) for myeloid malignancy (P=0.07 for heterogeneity); similarly, mature T-cell malignancies 1.36 (1.03-1.79), diffuse large B-cell lymphoma 1.28 (1.14-1.43), follicular lymphoma 1.28 (1.13-1.44), plasma cell neoplasms 1.12 (1.01-1.24), chronic lymphocytic leukaemia/small lymphocytic lymphoma 1.23 (1.08-1.40), and acute myeloid leukaemia 1.22 (1.04-1.42). There was no significant heterogeneity between subtypes. CONCLUSION: In middle-aged women, greater body mass index and height were associated with modestly increased risks of many subtypes of haematological malignancy.

Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol.

The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles. The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted.

Within-diver variability in venous gas emboli (VGE) following repeated dives.

Introduction: Venous gas emboli (VGE) are widely used as a surrogate endpoint instead of decompression sickness (DCS) in studies of decompression procedures. Peak post-dive VGE grades vary widely following repeated identical dives but little is known about how much of the variability in VGE grades is proportioned between-diver and within-diver. Methods: A retrospective analysis of 834 man-dives on six dive profiles with post-dive VGE measurements was conducted under controlled laboratory conditions. Among these data, 151 divers did repeated dives on the same profile on two to nine occasions separated by at least one week (total of 693 man-dives). Data were analysed for between- and within-diver variability in peak post-dive VGE grades using mixed-effect models with diver as the random variable and associated intraclass correlation coefficients. Results: Most divers produced a wide range of VGE grades after repeated dives on the same profile. The intraclass correlation coefficient (repeatability) was 0.33 indicating that 33% of the variability in VGE grades is between-diver variability; correspondingly, 67% of variability in VGE grades is within-diver variability. DCS cases were associated with an individual diver's highest VGE grades and not with their lower VGE grades. Conclusions: These data demonstrate large within-diver variability in VGE grades following repeated dives on the same dive profile and suggest there is substantial within-diver variability in susceptibility to DCS. Post-dive VGE grades are not useful for evaluating decompression practice for individual divers.

Alcohol drinking, tobacco smoking and subtypes of haematological malignancy in the UK Million Women Study.

BACKGROUND: Previous research suggests associations of lower alcohol intake and higher tobacco consumption with increased risks of haematological malignancy. The prospective Million Women Study provides sufficient power for reliable estimates of subtype-specific associations in women. METHODS: Approximately 1.3 million middle-aged women were recruited in the United Kingdom during 1996-2001 and followed for death, emigration and cancer registration until 2009 (mean 10.3 years per woman); potential risk factors were assessed by questionnaire. Adjusted relative risks were estimated by Cox regression. RESULTS: During follow-up, 9162 incident cases of haematological malignancy were recorded, including 7047 lymphoid and 2072 myeloid cancers. Among predominantly moderate alcohol drinkers, higher intake was associated with lower risk of lymphoid malignancies, in particular diffuse large B-cell lymphoma (relative risk 0.85 per 10 g alcohol per day (95% confidence interval 0.75-0.96)), follicular lymphoma (0.86 (0.76-0.98)) and plasma cell neoplasms (0.86 (0.77-0.96)). Among never- and current smokers, higher cigarette consumption was associated with increased risk of Hodgkin lymphoma (1.45 per 10 cigarettes per day (1.22-1.72)), mature T-cell malignancies (1.38 (1.10-1.73)) and myeloproliferative/myelodysplastic disease (1.42 (1.31-1.55)). CONCLUSION: These findings confirm and extend existing evidence for associations of subtypes of haematological malignancy with two common exposures in women.

Emotion modulates cognitive flexibility in patients with major depression.

BACKGROUND: Depression is associated with alterations of emotional and cognitive processing, and executive control in particular. Previous research has shown that depressed patients are impaired in their ability to shift attention from one emotional category to another, but whether this shifting deficit is more evident on emotional relative to non-emotional cognitive control tasks remains unclear. METHOD: The performance of patients with major depressive disorder and matched healthy control participants was compared on neutral and emotional variants of a dynamic cognitive control task that requires participants to shift attention and response from one category to another. RESULTS: Relative to controls, depressed patients were impaired on both tasks, particularly in terms of performance accuracy. In the neutral go/no-go task, the ability of depressed patients to flexibly shift attention and response from one class of neutral stimuli to the other was unimpaired. This contrasted with findings for the emotional go/no-go task, where responding was slower specifically on blocks of trials that required participants to shift attention and response from one emotional category to the other. CONCLUSIONS: The present data indicate that any depression-related difficulties with cognitive flexibility and control may be particularly evident on matched tasks that require processing of relevant emotional, rather than simply neutral, stimuli. The implications of these findings for our developing understanding of cognitive and emotional control processes in depression are discussed.

Poly(methyl methacrylate) coating of soft magnetic amorphous and crystalline Fe,Co-B nanoparticles by chemical reduction.

The structural and magnetic properties of a collection of nanoparticles coated by Poly(methyl methacrylate) through a wet chemical synthesis have been investigated. The particles display either an amorphous (M = Fe, Co) M-B arrangement or a mixed structure bcc-Fe and fcc-Co + amorphous M-B. Both show the presence of a metal oxi-hydroxide formed in aqueous reduction. The organic coating facilitates technological handling. The cost-effective synthesis involves a reduction in a Poly(methyl methacrylate) aqueous solution of iron(II) or cobalt(II) sulphates (< 0.5 M) by sodium borohydride (< 0.5 M). The particles present an oxidized component, as deduced from X-ray diffraction, Mössbauer and Fe- and Co K-edge X-ray absorption spectroscopy and electron microscopy. For the ferrous alloys, this Fe-oxide is alpha-goethite, favoured by the aqueous solution. The Poly(methyl methacrylate) coating is confirmed by Fourier transform infrared spectroscopy. In pure amorphous core alloys there is a drastic change of the coercivity from bulk to around 30 Oe in the nanoparticles. The mixed structured alloys also lie in the soft magnetic regime. Magnetisation values at room temperature range around 100 emu/g. The coercivity stems from multidomain particles and their agglomeration, triggering the dipolar interactions.

Asylum seekers and refugees in Northern Ireland: the impact of post-migration stressors on mental health.

OBJECTIVES: In recent years, Northern Ireland has seen an increase in the numbers of asylum seekers and refugees. Given its status as a post-conflict region, this is a relatively new phenomenon for the area. Northern Ireland is also the only part of the United Kingdom (UK) without a refugee integration strategy. In 2016, we conducted an extensive study for the racial equality unit of the Office of the First and Deputy First Minister in Stormont on the everyday life experience of asylum seekers and refugees in Northern Ireland with view to understanding how service delivery and notions of integration/inclusion impact. METHODS: This was a mixed methods study using quantitative survey methods and in-depth semi-structured interviews with service providers, asylum seekers, refugees and new UK citizens. We examined a range of service provision such as education, labour, legal provision, housing and health. RESULTS: This article examines the issue of mental health with respect to asylum seekers and refugees in Northern Ireland. The results delineate how asylum seekers and refugee's mental health is dramatically impacted by the asylum system in Northern Ireland (and hence, the UK) and the dearth thereof, of particular and necessary supports and access issues in the space of health and mental health in Northern Ireland. We describe how post-migration stressors experienced through the UK asylum system further compound mental health issues. The findings provide a focus on the asylum system, housing and employment. CONCLUSIONS: Our research found a dearth of mental health supports in Northern Ireland and concluded that the asylum system in the UK (as a form of post-migration stressor) further exacerbates and contributes to poor mental health and well-being for many asylum seekers and refugees.

Disease activity and treatment efficacy using patient-level Psoriasis Area and Severity Index scores from tildrakizumab phase 3 clinical trials.

BACKGROUND: It is unclear whether primary efficacy outcomes in plaque psoriasis clinical trials represent residual disease during treatment. OBJECTIVES: To evaluate supplementing dichotomous efficacy with residual disease activity. METHODS: This post hoc analysis used pooled, patient-level data after tildrakizumab 100 mg (N = 616) or placebo (N = 309) treatment from reSURFACE 1/2 (NCT01722331/NCT01729754) phase 3 clinical trials of patients with moderate to severe plaque psoriasis. RESULTS: Median baseline Psoriasis Area and Severity Index (PASI) was 17.9 for patients receiving tildrakizumab 100 mg. At Week 12, median PASI was 2.9, whereas dichotomous PASI 90 response rate was 36.9%, and absolute PASI <5.0, <3.0, and <1.0 were 64.0%, 50.8%, and 23.3%, respectively. At Week 28, median PASI was 1.7, whereas PASI 90 response rate was 51.9%, and absolute PASI <5.0, <3.0, and <1.0 were 75.3%, 62.8%, and 38.0%, respectively. Dermatology Life Quality Index and PASI scores were correlated through Week 28 (r = 0.51, p ≤ .0001). CONCLUSIONS: Disease activity was more reliably estimated by PASI scores than percentage PASI improvement; this may partially explain efficacy disparities between clinical trials and practice. These results suggest supplementing dichotomous PASI improvement with PASI scores and consideration of patient treatment goals could facilitate clinical decisions.

Developing Integrated Approaches for Testing and Assessment (IATAs) in order to support nanomaterial safety.

Due to the unique characteristics of nanomaterials (NM) there has been an increase in their use in nanomedicines and innovative medical devices (MD). Although large numbers of NMs have now been developed, comprehensive safety investigations are still lacking. Current gaps in understanding the potential mechanisms of NM-induced toxicity can make it challenging to determine the safety testing necessary to support inclusion of NMs in MD applications. This article provides guidance for implementation of pre-clinical tailored safety assessment strategies with the aim to increase the translation of NMs from bench development to clinical use. Integrated Approaches to Testing and Assessment (IATAs) are a key tool in developing these strategies. IATAs follow an iterative approach to answer a defined question in a specific regulatory context to guide the gathering of relevant information for safety assessment, including existing experimental data, integrated with in silico model predictions where available and appropriate, and/or experimental procedures and protocols for generating new data to fill gaps. This allows NM developers to work toward current guidelines and regulations, while taking NM specific considerations into account. Here, an example IATA for NMs with potential for direct blood contact was developed for the assessment of haemocompatibility. This example IATA brings together the current guidelines for NM safety assessment within a framework that can be used to guide information and data gathering for the safety assessment of intravenously injected NMs. Additionally, the decision framework underpinning this IATA has the potential to be adapted to other testing needs and regulatory contexts.

Risk of arterial thromboembolic events in patients with advanced colorectal cancer receiving bevacizumab.

BACKGROUND: Bevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab. PATIENTS AND METHODS: We recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C. RESULTS: Bevacizumab-treated patients had 12 grade 3, 4, or 5 ATEs (3.8% incidence). ATEs occurred in 2.1% of patients >65 years, 5% of those with a history of ATE, and 5% of those with cardiac risk factors. Age, history of ATE, or vascular risk factors did not increase risk. Aspirin users had a higher incidence than nonusers (8.9% versus 2.7%) but had higher rates of vascular risk factors. CONCLUSIONS: Bevacizumab was associated with a modestly higher risk of ATE, but safety was not significantly worse in older patients or patients with a history of ATE or vascular risk factors. The effect of aspirin in preventing ATE in patients receiving bevacizumab could not be determined from this study.

Controlled tissue expansion in the initial management of the short bowel state.

The treatment of short gut syndrome has evolved dramatically during the past decade. The combination of surgical techniques and medical management in the context of a multidisciplinary approach has improved the outcomes of these children. The authors describe in detail their technique of controlled tissue expansion of the bowel before lengthening procedures. Monitoring of the child and troubleshooting actions during the controlled tissue expansion program also are discussed.

The impact of teaching experimental research on-line: Research-informed teaching and COVID-19.

INTRODUCTION: As part of the BSc (Hons) Diagnostic Radiography programme students learn and undertake research relevant to their development as first post radiographers (dose optimisation and image quality) within the Research-Informed Teaching experience (RiTe). Due to the COVID-19 pandemic, the delivery of RiTe to our year 2 students was moved to an online format using Microsoft Teams and Blackboard Collaborate and focused on a key area of current practice - COVID-19 and chest X-ray imaging. Within RiTe students are placed into collaborative enquiry-based learning (CEBL) groups to share tasks, but to also support and learn from one another. METHODS: An online survey was used to explore the year 2 student cohort task value and self-efficacy of this online version of RiTe. RESULTS: A 73% (32/44) response rate was achieved. Students found the online version of RiTe to be a positive learning and development experience. There was strong agreement that they not only found it relevant to their area of practice (task-value), but also strongly agreed that they understood and could master the skills taught (self-efficacy). CONCLUSION: This online version of RiTe was effectively structured to help scaffold student learning and development of research data analysis skills despite the lack of face-to-face teaching. The students also valued the topic area (COVID-19 and chest X-ray imaging). A blended learning approach with RiTe will be used next year with a combination of collaborative online teaching and physical data collection and analysis in the university-based X-ray imaging laboratory. Further evaluation and data collection will also be undertaken. IMPLICATIONS FOR PRACTICE: University-based empirical work in groups to learn about research can be replaced by an online mechanism whilst still maintaining task-value and acceptable self-efficacy.

Problem based learning in radiography education: A narrative review.

OBJECTIVES: Radiography practice is fast developing with new imaging updates and challenging scenarios to deal with on a frequent basis. There is a need to equip students with the skill to be independent learners and develop critical thinking skills, so they can change their practice as the profession evolves. Problem Based Learning (PBL) has widely been adopted in medical and nursing training worldwide as a result of its desirable benefits. In order to ascertain the efficacy of the technique, this paper presents a review of the essential aspects of PBL, such as the theories, process, key roles and implication for radiography education and practice. KEY FINDINGS: The use of a defined model provides a useful structure to the PBL exercise with the addition of reflection, which is a pertinent inclusion within the process. The role of the facilitator in PBL is significant to students' learning as they help guide the students to the learning outcomes and provide support to the group; however, their skills development is an important factor to consider in PBL. CONCLUSION: This teaching approach has key benefits in radiography education and training in particular, its impact on preparing students for autonomous clinical practice. IMPLICATIONS FOR PRACTICE: The application of PBL in developing students' critical thinking and decision-making abilities support the narrowing of the spoon-feeding expectation of students and render it a useful pedagogical implementation within radiography programmes.

Hemodialysis catheter integrity during mechanical power injection of iodinated contrast medium for computed tomography angiography.

PURPOSE: CT angiography (CTA) requires vascular access with flow rates of 5-7 mL/s. Hemodialysis (HD) is performed at 6-10 mL/s. The purpose of our study is to evaluate the structural integrity of HD catheters in the administration of contrast media via a mechanical power injector under varying conditions. METHODS: Four HD catheters were evaluated in an in vitro study. Tested were contrast media type (iopamidol 300 and 370 mgI/mL), temperature (25 and 37 °C), catheter diameter (14 Fr to 16 Fr all with double-lumen capacity), catheter length (19-32 cm), and simultaneous double-lumen or single-lumen injection within each of the catheters. Peak plateau pressures (psi) were recorded with flow rates from 5 to 20 mL/s in 5 mL/s increments. In total, 864 unique injections were performed. RESULTS: No catheter failure (bulging/rupture) was observed in 864 injections. Maximum pressure for single-lumen injection was 51.7 psi (double-lumen: 26.3 psi). Peak pressures were significantly lower in simultaneous double-lumen vs. single-lumen injections (p < 0.001) and low vs. high viscosity contrast media (p < 0.001). Neither larger vs. smaller diameter lumens (p = 0.221) nor single-lumen injection in arterial vs. venous (p = 0.834) were significantly different. CONCLUSION: HD catheters can be used to safely administer iodinated contrast media via mechanical power injection in in vitro operating conditions. Maximum peak pressure is below the manufacturer's 30 psi limit at flow rates up to 20 mL/s in double-lumen injections and up to 10 mL/s in single-lumen injections, which is higher than the usual maximum of 8 mL/s for CT angiography in clinical settings.

Immunopathology of lymphocytic choriomeningitis viurs infection of newborn mice. Antithymocyte serum effects on glomerulonephritis and wasting disease.

Antithymocyte serum, when administered neonatally to mice, delayed the maturation of the lymphoid system, permitting development of cellular tolerance to LCM virus at an older age than is ordinarily possible. Humoral antibody formation was not prevented and the animals exhibited the paradox of high titers of both circulating virus and antibody. This, in turn, was followed by a chronic immunopathologic glomerulonephritis in most animals. Some animals developed wasting disease between 1 and 2 months of age, characterized by reticular cell hyperplasia and widespread infiltration into tissues and organs.

Cellular immunity in vaccinia infection of mice. Anti-thymocyte serum effects on primary and secondary responsiveness.

Rabbit anti-mouse thymocyte serum suppressed host cell-mediated responsiveness to intravenously administered vaccinia virus, thereby augmenting the morbidity and mortality of this infection. It did not affect either humoral antibody or interferon production in response to vaccinia virus. No effects were noted on primary or secondary immunity to intracerebral virus inoculation.

The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study.

BACKGROUND: Recent studies suggest that blockade of the NLRP3 (cryopyrin) inflammasome interleukin 1beta (IL1beta) pathway may offer a new treatment strategy for gout. OBJECTIVE: To explore the potential utility of rilonacept (IL1 Trap) in patients with chronic active gouty arthritis in a proof-of-concept study. METHODS: This 14-week, multicentre, non-randomised, single-blind, monosequence crossover study of 10 patients with chronic active gouty arthritis included a placebo run-in (2 weeks), active rilonacept treatment (6 weeks) and a 6-week post-treatment follow-up. RESULTS: Rilonacept was generally well tolerated. No deaths and no serious adverse events occurred during the study. One patient withdrew owing to an injection-site reaction. Patients' self-reported median pain visual analogue scale scores significantly decreased from week 2 (after the placebo run-in) to week 4 (2 weeks of rilonacept) (5.0 to 2.8; p<0.049), with sustained improvement at week 8 (1.3; p<0.049); 5 of 10 patients reported at least a 75% improvement. Median symptom-adjusted and severity-adjusted joint scores were significantly decreased. High-sensitivity C-reactive protein levels fell significantly. CONCLUSIONS: This proof-of-concept study demonstrated that rilonacept is generally well tolerated and may offer therapeutic benefit in reducing pain in patients with chronic refractory gouty arthritis, supporting the need for larger, randomised, controlled studies of IL1 antagonism such as with rilonacept for this clinical indication.