Analysis of gout remission definitions in a randomised controlled trial of colchicine prophylaxis for people with gout initiating allopurinol.

OBJECTIVE: To investigate the effect of colchicine prophylaxis on gout remission when commencing urate lowering therapy (ULT), and illness perceptions of people in remission, using two definitions of gout remission. METHODS: Data from a 12-month double-blind placebo-controlled trial of 200 people with gout commencing allopurinol were analyzed. Participants were randomly assigned to prophylaxis with 0.5mg daily colchicine or placebo for six months, followed by six months of additional follow-up. Gout remission was assessed using the 2016 preliminary definition or simplified definition without patient reported outcomes. Illness perceptions were assessed using a gout-specific brief illness perception questionnaire (BIPQ). RESULTS: In the first six months, few participants were in remission according to either the 2016 preliminary definition (3% for colchicine and 4% for placebo) or the simplified definition (7% for colchicine and 12% for placebo). In the second six months, after study drug (colchicine or placebo) discontinuation, fewer participants in the colchicine group than in the placebo group were in remission according to the 2016 preliminary definition (4% vs. 14%, p=0.03), and the simplified definition (14% vs 28%, p=0.02). Participants fulfilling remission using either definition had more favorable perceptions about their gout symptoms and illness concerns, as well as consequences, when using the simplified definition. CONCLUSION: Using either definition, six months of colchicine prophylaxis when initiating ULT does not provide an advantage in the fulfilment of gout remission. People fulfilling either definition report fewer symptoms, lower concern about their gout, and when using the simplified definition, are less affected by gout.

The endolysosomal system in conventional and unconventional protein secretion.

Most secreted proteins are transported through the "conventional" endoplasmic reticulum-Golgi apparatus exocytic route for their delivery to the cell surface and release into the extracellular space. Nonetheless, formative discoveries have underscored the existence of alternative or "unconventional" secretory routes, which play a crucial role in exporting a diverse array of cytosolic proteins outside the cell in response to intrinsic demands, external cues, and environmental changes. In this context, lysosomes emerge as dynamic organelles positioned at the crossroads of multiple intracellular trafficking pathways, endowed with the capacity to fuse with the plasma membrane and recognized for their key role in both conventional and unconventional protein secretion. The recent recognition of lysosomal transport and exocytosis in the unconventional secretion of cargo proteins provides new and promising insights into our understanding of numerous physiological processes.

Understanding the Role of Layered Minerals in the Emergence and Preservation of Proto-Proteins and Detection of Traces of Early Life.

ConspectusThe origin of life remains one of the most profound mysteries in science. Over millennia, theories have evolved, yet the question persists: How did life emerge from inanimate matter? At its core, the study of life's origin offers insights into our place in the universe and the nature of life itself. By delving into the chemical and geological processes that led to life's emergence, scientists gain a deeper understanding of the fundamental principles that govern living systems. This knowledge not only expands our scientific understanding but also has profound implications for fields ranging from astrobiology to synthetic biology.This research employs a multidisciplinary approach, combining a diverse array of techniques, from space missions to wet laboratory experiments to theoretical modeling. Investigations into the formation of the first proto-biomolecules are tailored to explore both the complex molecular processes that underpin life and the geological contexts in which these processes may have occurred. While laboratory experiments are aimed at mimicking the processes of early planets, not every process and sample is attainable. To this end, we demonstrate the use of molecular modeling techniques to complement experimental efforts and extraterrestrial missions. The simulations enable researchers to test hypotheses and explore scenarios that are difficult or impossible to replicate in the laboratory, bridging gaps in our understanding of prebiotic processes across vast time and space scales.Minerals, particularly layered structures like clays and hydrotalcites, play diverse and pivotal roles in the origin of life. They concentrate organic species, catalyze polymerization reactions (such as peptide formation), and provide protective environments for the molecules. Minerals have also been suggested to have acted as primitive genetic materials. Nevertheless, they may lack the ability for long-term information replication. Instead, we suggest that minerals may act as transcribers of information encoded in environmental cyclic phenomena, such as tidal or seasonal changes. We argue that extensive protection of the produced polymer will immobilize it, making it inactive for any further function. Therefore, in order to generate a functional polymer, it is essential that it remains mobile and chemically active. Furthermore, we suggest a route to the identification of pseudobiosignatures, a polymer that was polymerized on the same mineral surface and consequently retained through overprotection.This Account presents a comprehensive evaluation of the current understanding of the role of layered mineral surfaces on life's origin and biosignature preservation. It highlights the complexity of mineral-organic interactions and proposes pathways for proto-biomolecule emergence and methods for identifying and interpreting potential biosignatures. Ultimately, the quest to uncover the origin of life continues to drive scientific exploration and innovation, offering profound insights into the fundamental nature of existence and our place in the universe.

Baseline dual energy computed tomography urate volume predicts fulfillment of gout remission after two years of urate-lowering therapy.

OBJECTIVE: This study aimed to identify variables that predict gout remission in people with erosive gout receiving urate-lowering therapy. METHODS: We analysed data from a 2-year, double-blind randomized-controlled trial of people with erosive gout, randomized to a serum urate target of <0.20mmol/l or <0.30mmol/l using oral urate-lowering therapies. All participants had dual energy CT (DECT) scans of the feet and ankles at baseline. The proportion of participants achieving gout remission according to the 2016 preliminary gout remission criteria and simplified gout remission criteria (without the patient reported outcomes) was analyzed. Logistic regression models were used to evaluate predictors of gout remission in Year 2. RESULTS: The preliminary gout remission criteria were fulfilled in 11/97 (11%) participants at Year 1 and 21/92 (23%) participants at Year 2. The simplified criteria were fulfilled in 26/97 (27%) participants in Year 1 and 40/92 (44%) participants in Year 2. In multivariable regression models, baseline DECT monosodium urate crystal volume was the only significant independent predictor of gout remission at Year 2, using either criteria. Each one cm3 increase in the baseline DECT monosodium urate crystal volume decreased the odds of fulfilling the 2016 preliminary gout remission criteria (0.65 [95% CI 0.46-0.93], p=0.02), and the simplified gout remission criteria (0.57 [95% CI 0.41-0.78], p<0.001). CONCLUSIONS: In people with erosive gout on urate-lowering therapy, higher baseline DECT monosodium urate crystal volume is associated with lower odds of gout remission after two years of treatment, defined by either the preliminary gout remission criteria or simplified gout remission criteria.

miR-182, miR-221 and miR-222 are potential urinary extracellular vesicle biomarkers for canine urothelial carcinoma.

Current diagnostic methods for canine urothelial carcinoma (UC) are technically challenging or can lack specificity, hence there is a need for novel biomarkers of UC. To this end, we analysed the microRNA (miRNA) cargo of extracellular vesicles (EVs) from urine samples of dogs with UC to identify candidate miRNA biomarkers. Urine was fractionated using ultrafiltration combined with size-exclusion chromatography and small RNA sequencing analysis was performed on both the EV enriched and (EV free) protein fractions. A greater number of candidate miRNA biomarkers were detected in the EV fraction than the protein fraction, and further validation using droplet digital PCR (ddPCR) was performed on the EV enriched fraction of a second cohort of dogs with UC which indicated that miR-182, miR-221 and miR-222 were significantly overrepresented in dogs with UC when compared with healthy dogs and dogs with urinary tract infections. Pathway analysis confirmed that these three miRNAs are involved in cancer. In addition, their potential downstream gene targets were predicted and PIK3R1, a well-known oncogene is likely to be a shared target between miRNA-182 and miRNA-221/222. In summary, this study highlights the potential of urinary EV-associated miRNAs as a source of biomarkers for the diagnosis of canine UC.

Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.

Trithorax-related H3K4 methyltransferases, KMT2C and KMT2D, are critical epigenetic modifiers. Haploinsufficiency of KMT2C was only recently recognized as a cause of neurodevelopmental disorder (NDD), so the clinical and molecular spectrums of the KMT2C-related NDD (now designated as Kleefstra syndrome 2) are largely unknown. We ascertained 98 individuals with rare KMT2C variants, including 75 with protein-truncating variants (PTVs). Notably, ∼15% of KMT2C PTVs were inherited. Although the most highly expressed KMT2C transcript consists of only the last four exons, pathogenic PTVs were found in almost all the exons of this large gene. KMT2C variant interpretation can be challenging due to segmental duplications and clonal hematopoesis-induced artifacts. Using samples from 27 affected individuals, divided into discovery and validation cohorts, we generated a moderate strength disorder-specific KMT2C DNA methylation (DNAm) signature and demonstrate its utility in classifying non-truncating variants. Based on 81 individuals with pathogenic/likely pathogenic variants, we demonstrate that the KMT2C-related NDD is characterized by developmental delay, intellectual disability, behavioral and psychiatric problems, hypotonia, seizures, short stature, and other comorbidities. The facial module of PhenoScore, applied to photographs of 34 affected individuals, reveals that the KMT2C-related facial gestalt is significantly different from the general NDD population. Finally, using PhenoScore and DNAm signatures, we demonstrate that the KMT2C-related NDD is clinically and epigenetically distinct from Kleefstra and Kabuki syndromes. Overall, we define the clinical features, molecular spectrum, and DNAm signature of the KMT2C-related NDD and demonstrate they are distinct from Kleefstra and Kabuki syndromes highlighting the need to rename this condition.

Burnout among the podiatry profession: A survey of podiatrists in Aotearoa New Zealand.

INTRODUCTION: Burnout and occupational stress have not yet been explored within the Aotearoa New Zealand (AoNZ) podiatry workforce despite research suggesting an increased risk among this population. This study aimed to: (i) determine the prevalence and severity of burnout risk and occupational stress among AoNZ podiatrists; (ii) determine the factors associated with burnout risk and occupational stress among AoNZ podiatrists; and (iii) examine the relationship between burnout risk and occupational stress. METHODS: A cross-sectional online survey study was undertaken involving registered podiatrists practicing in AoNZ. Personal and professional demographic characteristics were captured. Participants also completed the Maslach Burnout Inventory (assessing three domains of emotional exhaustion, depersonalisation and personal accomplishment) and the Workplace Stress Scale as measures of burnout risk and occupational stress, respectively. Descriptive statistics, multiple regression analyses and correlation analyses were performed to address the research aims. RESULTS: Responses from 112 AoNZ podiatrists were included in the analyses. High levels of emotional exhaustion were identified in 43.8% of practitioners and were associated with physical activity status, sector of work, working in isolation and work hours (R2 = 0.304, F (8, N = 110) = 5.519, p < 0.001). High levels of depersonalisation were seen in 13.4% of practitioners and were associated with patient caseload and work hours, (R2 = 0.183, F (4, N = 108) = 5.770, p < 0.001). Low levels of personal accomplishment were observed in 8.9% of practitioners and associated with ethnicity, physical activity status and patient caseload, (R2 = 0.152, F (5, N = 106) = 3.577, p < 0.005). A total of 27.7% of practitioners exhibited an overall moderate to high risk of developing burnout. Over a fifth of practitioners exhibited stress at severe or dangerous levels. Stress levels were significantly associated with physical activity status, sector of work and management responsibility, (R2 = 0.282, F (5, N = 47) = 3.218, p = 0.15). A strong positive relationship was found between emotional exhaustion and stress (rho = 0.59, p < 0.001). CONCLUSIONS: The findings reflect a moderate to severe risk of developing burnout within the workforce, with high workloads and collegial isolation constituting the primary modifiable factors driving burnout development. To maintain retention and well-being within the workforce, mitigation strategies must be implemented to address this issue.

The use of antimicrobial dressings for the management of diabetic foot ulcers: A survey of podiatrists in Aotearoa New Zealand.

INTRODUCTION: Diabetic foot ulcers (DFUs) are commonly contaminated with pathogenic organisms and precede most diabetes-related amputations. Antimicrobial dressings are used in the treatment of DFUs; however, recent guidelines do not support their use. There are no data describing the experience of antimicrobial dressing use among podiatrists in Aotearoa New Zealand (AoNZ). This study aimed to (i) determine which antimicrobial dressings podiatrists in AoNZ use for the management of diabetic foot ulcers; and (ii) determine what factors influence AoNZ podiatrists' use of antimicrobial dressing when managing DFUs. METHODS: An anonymous cross-sectional web-based survey was undertaken. Participants were AoNZ registered podiatrists who managed DFUs in their practice. The survey included questions relating to personal and professional demographic characteristics and DFU management and dressing practices. Descriptive statistics were computed to address the research aims. RESULTS: Responses from 43 AoNZ podiatrists were included. Participants reported both cadexomer iodine and silver dressings were the most common antimicrobial dressings used, with honey dressings being the least frequently used. The most influential factors in choosing antimicrobial dressings when managing DFUs were the presence of current infection, ulcer exudate and ability to prevent future infection. The least influential factors in choosing antimicrobial dressings when managing DFUs were patient preferences, cost of dressings and comfort of dressing/pain on removal. CONCLUSIONS: AoNZ podiatrists managing DFUs primarily use antimicrobial dressings containing cadexomer iodine or silver as active ingredients, while lower-cost options, such as honey and povidone iodine are less often used. Current recommendations highlight the lack of evidence to support positive outcomes from any particular antimicrobial dressing over another and advocate that exudate control, comfort and cost be prioritised in decision-making. As cost has been an increasing burden to our healthcare funding, clinicians and organisations may consider this before purchasing and stocking expensive dressings.

The development of recommendations for the assessment and management of sesamoiditis by podiatrists: A Delphi and content validity study.

INTRODUCTION: Sesamoiditis is a common, and often painful, musculoskeletal pathology frequently encountered by podiatrists. However, there are currently no recommendations to guide podiatrists in the assessment and management of people with sesamoiditis. The aim of this study was to develop consensus-driven clinical recommendations on the assessment and management of people with sesamoiditis. METHODS: A four-round online Delphi survey was conducted with a panel of New Zealand and Australian podiatrists. In the first round, panellists answered open-ended questions that were used to create statements. In round two, the panellists scored the statements from 1 to 9 (1 = not at all important, 9 = absolutely essential). Consensus was defined using the RAND/University of California Los Angles Disagreement Index. Panellists were asked to reconsider statements that did not achieve consensus in round three. In the final round, content validity and acceptability of the statements for inclusion in clinical recommendations were determined using content validity ratios and the Content Validity Index (CVI). RESULTS: Eighteen panellists completed round one with 16 (89%) completing all four rounds. A total of 118 statements were generated following round one. Following rounds two and three, 78 statements were accepted by panellists as being important, with 62 statements achieving sufficient content validity for inclusion in clinical recommendations. The CVI for these 62 statements was 0.58. These recommendations provide guidance on subjective assessment (pain characteristics/symptomology, activity/sports/training history and medical history) objective assessment (establishing a diagnosis, identifying contributing biomechanical factors, footwear/orthoses, ruling out differential diagnoses) and management (temporary padding/strapping, education, footwear, foot orthoses and when to consider referral). CONCLUSION: This consensus exercise has provided a set of consensus-based recommendations for the assessment and management of people with sesamoiditis. In the current absence of research-based evidence in this area, these recommendations are intended to support clinicians. The recommendations may also serve as a basis for future clinical trials evaluating the efficacy of conservative interventions for people with sesamoiditis.

Objective grading of rib eye traits using the Q-FOM™ camera in Australian beef carcasses.

The objective of this study was to develop calibration models against rib eye traits and independently validate the precision, accuracy, and repeatability of the Frontmatec Q-FOM™ Beef grading camera in Australian carcasses. This study compiled 12 different research datasets acquired from commercial processing facilities and were comprised of a diverse range of carcass phenotypes, graded by industry identified expert Meat Standards Australia (MSA) graders and sampled for chemical intramuscular fat (IMF%). Calibration performance was maintained when the device was independently validated. For continuous traits, the Q-FOM™ demonstrated precise (root mean squared error of prediction, RMSEP) and accurate (coefficient of determination, R2) prediction of eye muscle area (EMA) (R2 = 0.89, RMSEP = 4.3 cm2, slope = 0.96, bias = 0.7), MSA marbling (R2 = 0.95, RMSEP = 47.2, slope = 0.98, bias = -12.8) and chemical IMF% (R2 = 0.94, RMSEP = 1.56%, slope = 0.96, bias = 0.64). For categorical traits, the Q-FOM™ predicted 61%, 64.3% and 60.8% of AUS-MEAT marbling, meat colour and fat colour scores equivalent, and 95% within ±1 classes of expert grader scores. The Q-FOM™ also demonstrated very high repeatability and reproducibility across all traits.

Identifying determinants of adherence to adjuvant endocrine therapy following breast cancer: A systematic review of reviews.

BACKGROUND: In oestrogen-receptor positive breast cancer, daily oral adjuvant endocrine therapy (ET) for at least 5 years significantly reduces risks of recurrence and breast cancer-specific mortality. However, many women are poorly adherent to ET. Development of effective adherence support requires comprehensive understanding of influences on adherence. We undertook an umbrella review to identify determinants of ET adherence. METHODS: We searched PubMed, Embase, CINAHL, PsycINFO, Cochrane and PROSPERO (inception to 08/2022) to identify systematic reviews on factors influencing ET adherence. Abstracted determinants were mapped to the World Health Organization's dimensions of adherence. Reviews were quality appraised and overlap assessed. RESULTS: Of 5732 citations screened, 17 reviews were eligible (9 quantitative primary studies; 4 qualitative primary studies; 4 qualitative or quantitative studies) including 215 primary papers. All five WHO dimensions influenced ET non-adherence: The most consistently identified non-adherence determinants were patient-related factors (e.g. lower perceived ET necessity, more treatment concerns, perceptions of ET 'cons' vs. 'pros'). Healthcare system/healthcare professional-related factors (e.g. perceived lower quality health professional interaction/relationship) were also important and, to a somewhat lesser extent, socio-economic factors (e.g. lower levels of social/economic/material support). Evidence was more mixed for medication-related and condition-related factors, but several may be relevant (e.g. experiencing side-effects, cost). Potentially modifiable factors are more influential than non-modifiable/fixed factors (e.g. patient characteristics). CONCLUSIONS: The evidence-base on ET adherence determinants is extensive. Future empirical studies should focus on less well-researched areas and settings. The determinants themselves are numerous and complex in indicating that adherence support should be multifaceted, addressing multiple determinants.

An updated systematic review and meta-analysis of randomised controlled trials on the effects of urate-lowering therapy initiation during a gout flare.

BACKGROUND: There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the effects of ULT initiation during a gout flare. METHODS: This systematic review was conducted in accordance with PRISMA methodology. MEDLINE, EMBASE and The Cochrane Library were searched for studies published between database inception to 1 March 2023. RCTs published in English that examined ULT initiation during a gout flare in adults ≥18 years were included. The quality of included studies was assessed using the revised Cochrane Risk of Bias tool 2.0. Data were extracted for the following outcomes: patient-rated pain score, duration of gout flare, recurrent gout flares, time to achieve target serum urate, adherence to ULT, patient satisfaction with treatment and adverse events. Meta-analyses were performed using Review Manager v5.4. This study is registered on PROSPERO, number CRD42023404680. RESULTS: A total of 972 studies were identified and of these, six RCTs met the criteria for inclusion in the analysis. Three studies were assessed as having high risk of bias, one study as having some concerns, and two studies as having low risk of bias. In total, there were 445 pooled participants; 226 participants randomised to early initiation of ULT and 219 to placebo or delayed initiation of ULT. Allopurinol was used in three studies, febuxostat in two studies and probenecid in one study. Few participants (n = 62, 13.9 %) had tophaceous gout. Participants with renal impairment were excluded from most studies. There were no differences in patient-rated pain scores at baseline, days 3-4, days 7-8, day 10 or days 14-15 (p ≥ 0.42). Additionally, there was no significant difference in time to resolution of gout flare (standardised mean difference 0.77 days; 95 % CI -0.26 to 1.79; p = 0.14) or the risk of recurrent gout flare in the subsequent 28 to 30 days (RR 1.06; 95 % CI 0.59 to 1.92; p = 0.84). Adverse events were similar between groups. The included studies did not report time to achieve target serum urate, long-term adherence to ULT, or patient satisfaction with treatment. CONCLUSION: There appears to be no evidence for harm or for benefit to initiating ULT during a gout flare. These findings have limited applicability to patients with tophaceous gout, or those with renal impairment.

Time-Series Analysis of First-Time Pediatric Speech Delays From 2018 to 2022.

This cohort study evaluates changes in pediatric speech delay diagnoses before and after the COVID-19 pandemic.

UK clinicians' attitudes towards the application of molecular diagnostics to guide antibiotic use in ICU patients with pneumonias: a quantitative study.

BACKGROUND: Molecular diagnostic tests may improve antibiotic prescribing by enabling earlier tailoring of antimicrobial therapy. However, clinicians' trust and acceptance of these tests will determine their application in practice. OBJECTIVES: To examine ICU prescribers' views on the application of molecular diagnostics in patients with suspected hospital-acquired and ventilator-associated pneumonia (HAP/VAP). METHODS: Sixty-three ICU clinicians from five UK hospitals completed a cross-sectional questionnaire between May 2020 and July 2020 assessing attitudes towards using molecular diagnostics to inform initial agent choice and to help stop broad-spectrum antibiotics early. RESULTS: Attitudes towards using molecular diagnostics to inform initial treatment choices and to stop broad-spectrum antibiotics early were nuanced. Most (83%) were positive about molecular diagnostics, agreeing that using results to inform broad-spectrum antibiotic prescribing is good practice. However, many (58%) believed sick patients are often too unstable to risk stopping broad-spectrum antibiotics based on a negative result. CONCLUSIONS: Positive attitudes towards the application of molecular diagnostics to improve antibiotic stewardship were juxtapositioned against the perceived need to initiate and maintain broad-spectrum antibiotics to protect unstable patients.

Vesiclepedia 2024: an extracellular vesicles and extracellular particles repository.

Vesiclepedia (http://www.microvesicles.org) is a free web-based compendium of DNA, RNA, proteins, lipids and metabolites that are detected or associated with extracellular vesicles (EVs) and extracellular particles (EPs). EVs are membranous vesicles that are secreted ubiquitously by cells from all domains of life from archaea to eukaryotes. In addition to EVs, it was reported recently that EPs like exomeres and supermeres are secreted by some mammalian cells. Both EVs and EPs contain proteins, nucleic acids, lipids and metabolites and has been proposed to be implicated in several key biological functions. Vesiclepedia catalogues proteins, DNA, RNA, lipids and metabolites from both published and unpublished studies. Currently, Vesiclepedia contains data obtained from 3533 EV studies, 50 550 RNA entries, 566 911 protein entries, 3839 lipid entries, 192 metabolite and 167 DNA entries. Quantitative data for 62 822 entries from 47 EV studies is available in Vesiclepedia. The datasets available in Vesiclepedia can be downloaded as tab-delimited files or accessible through the FunRich-based Vesiclepedia plugin.

Virtual Reality for Pain Management During High-Resolution Manometry: A Randomized Clinical Trial.

OBJECTIVE: High-resolution esophageal manometry (HRM) is the gold standard for the diagnosis of esophageal motility disorders. HRM is typically performed in the office with local anesthesia only, and many patients find it unpleasant and painful. The aim of this study was to examine the effects of the use of a virtual reality (VR) headset on pain and anxiety outcomes in patients with dysphagia undergoing HRM. METHODS: Patients with dysphagia were prospectively recruited and randomized to undergo HRM with and without VR distraction. Data collected included the State-Trait Anxiety Inventory-6 (STAI-6), the Short-Form McGill Pain Questionnaire, heart rate, and galvanic skin response (GSR) tracings. RESULTS: Forty subjects completed the study, including 20 subjects in the intervention arm and 20 in the control arm. There was evidence of a significant positive effect of VR on calmness (p = 0.0095) STAI-6 rating, as well as on physiologic measures of pain with significantly decreased GSR rise time (p = 0.0137) and average rate of change of conductance change (p = 0.0035). CONCLUSION: The use of VR during HRM catheter insertion increased calmness compared to control. Change of skin conductance was also reduced in the VR group, suggesting decreased physiologic pain. This study supports the consideration of the use of VR as a distraction tool to improve patient comfort during HRM. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1118-1126, 2024.

Do Dynamic Plantar Pressures Differ Based on Sonographic Evidence of Metatarsophalangeal Joint Synovitis in People With Rheumatoid Arthritis?

OBJECTIVE: The metatarsophalangeal joints (MTPJs) are the most common location for synovitis in people with rheumatoid arthritis (RA), yet their association with plantar foot pressures has received very little attention. This study aimed to determine whether plantar pressures differed based on sonographic evidence of MTPJ synovitis in people with RA. METHOD: Ultrasound was used to assess synovitis (grey scale synovial hypertrophy and power Doppler signal) in MTPJs 1 to 5 using the combined EULAR/Outcome Measures in Rheumatology scoring system. Peak pressure (PP) and pressure time integrals (PTIs) were assessed during barefoot walking for seven plantar foot regions (heel, midfoot, first metatarsal, second metatarsal, third to fifth metatarsals, hallux, lesser toes). Mixed-effects linear regression was used to determine the difference in PP and PTI between MTPJs with none/minimal synovitis and MTPJs with moderate/severe synovitis. RESULTS: Thirty-five participants with RA were included. Mean age was 66.3 years and mean disease duration was 22.2 years. Participants with sonographic evidence of moderate/severe synovitis at the first MTPJ had reduced PTI at the hallux compared with those with none/minimal synovitis at this joint (P = 0.039). Participants with moderate/severe synovitis at the second MTPJ and fourth MTPJ had reduced PP and reduced PTI at lesser toes compared with those with none/minimal synovitis in these joints (all P ≤ 0.048). No significant differences were observed for synovitis in other joints. CONCLUSION: These findings may be suggestive of an inverse relationship between plantar pressure and soft tissue pathology, which is consistent with an offloading strategy and reduced use of the toes during propulsion.

The statistical challenge of analysing changes in dual energy computed tomography (DECT) urate volumes in people with gout.

BACKGROUND: Dual energy computed tomography (DECT) allows direct visualization of monosodium urate crystal deposition in gout. However, DECT urate volume data are often highly skewed (mostly small volumes with the remainder considerably larger), making statistical analyses challenging in longitudinal research. The aim of this study was to explore the ability of various analysis methods to normalise DECT urate volume data and determine change in DECT urate volumes over time. METHODS: Simulated datasets containing baseline and year 1 DECT urate volumes for 100 people with gout were created from two randomised controlled trials. Five methods were used to transform the DECT urate volume data prior to analysis: log-transformation, Box-Cox transformation, log(X-(min(X)-1)) transformation; inverse hyperbolic sine transformation, and rank order. Linear regression analyses were undertaken to determine the change in DECT urate volume between baseline and year 1. Cohen's d were calculated as a measure of effect size for each data treatment method. These analyses were then tested in a validation clinical trial dataset containing baseline and year 1 DECT urate volumes from 91 people with gout. RESULTS: No data treatment method successfully normalised the distribution of DECT urate volumes. For both simulated and validation data sets, significant reductions in DECT urate volumes were observed between baseline and Year 1 across all data treatment methods and there were no significant differences in Cohen's d effect sizes. CONCLUSIONS: Normalising highly skewed DECT urate volume data is challenging. Adopting commonly used transformation techniques may not significantly improve the ability to determine differences in measures of central tendency when comparing the change in DECT urate volumes over time.