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Importance: Approximately 12 million adults in the US have a history of gout, but whether serum urate levels can help predict recurrence is unclear., Objective: To assess associations of a single serum urate measurement with subsequent risk of acute gout flares and subsequent risk of hospitalizations for gout among patients in the UK with a history of gout., Design, Setting, and Participants: This retrospective study included patients with a history of gout identified from the UK between 2006 and 2010 who were followed up through Primary Care Linked Data medical record linkage until 2017 and through the Hospital Episode Statistics database until 2020., Exposures: Serum urate levels at enrollment., Main Outcome and Measure: Rate of recurrent acute gout, ascertained by hospitalization, outpatient, and prescription/procedure records, and adjusted rate ratios using negative binomial regressions., Results: Among 3613 patients with gout (mean age, 60 years; 3104 [86%] men), 1773 gout flares occurred over a mean follow-up of 8.3 years. Of these, 1679 acute gout flares (95%) occurred in people with baseline serum urate greater than or equal to 6 mg/dL and 1731 (98%) occurred in people with baseline serum urate greater than or equal to 5 mg/dL. Rates of acute gout flares per 1000 person-years were 10.6 for participants with baseline urate levels less than 6 mg/dL, 40.1 for levels of 6.0 to 6.9 mg/dL, 82.0 for levels of 7.0 to 7.9 mg/dL, 101.3 for levels of 8.0 to 8.9 mg/dL, 125.3 for urate levels of 9.0 to 9.9 mg/dL, and 132.8 for levels greater than or equal to 10 mg/dL. Rate ratio of flares were 1.0, 3.37, 6.93, 8.67, 10.81, and 11.42, respectively, over 10 years (1.61 [1.54-1.68] per mg/dL). Rates of hospitalization per 1000 person-years during follow-up were 0.18 for those with baseline serum urate less than 6 mg/dL, 0.97 for serum urate of 6.0 to 6.9 mg/dL, 1.8 for serum urate of 7.0 to 7.9 mg/dL, 2.2 for serum urate of 8.0 to 8.9 mg/dL, 6.7 for serum urate of 9.0 to 9.9 mg/dL, and 9.7 for serum urate greater than or equal to 10 mg/dL. Rate ratios of hospitalization for gout, adjusting for age, sex, and race were 1.0, 4.70, 8.94, 10.37, 33.92, and 45.29, respectively (1.87 [1.57-2.23] per mg/dL)., Conclusions and Relevance: In this retrospective study of patients with a history of gout, serum urate levels at baseline were associated with the risk of subsequent gout flares and rates of hospitalization for recurrent gout. These findings support using a baseline serum urate level to assess risk of recurrent gout over nearly 10 years of follow-up.

Background: Gout is the most common inflammatory arthritis and is almost exclusively managed in primary care, however the course and severity of the condition is variable and poorly characterised. This research aims improve understanding about the frequency of, and factors associated with, gout flares in the UK and characterise the factors associated with the initiation of ULT., Methods: Using the Clinical Practice Research Database, patients with a coded incident gout diagnosis without a prior prescription for urate-lowering therapy (ULT) were identified. Gout flares post diagnosis and ULT initiation were identified through prescribing and coded data. Patient characteristics, co-morbidities and co-prescribing were co-variants. Factors associated with gout flares and ULT initiation were analysed using cox-proportional hazard model and logistic regression., Results: Fifty-one thousand seven hundred eighty-four patients were identified: 18,605 (35.9%, 95%CI 35.5-36.3%) had experienced ≥ 1 recurrent flare, 17.4% (95%CI 17.1-17.8%) within 12 months of diagnosis. Male sex, black ethnicity, higher BMI, heart failure, CKD, CVD and diuretic use were associated with flares, with the highest HR seen with high serum urate levels (≥ 540 µmol/L HR 4.63, 95%CI 4.03-5.31). ULT initiation was associated with similar variables, although higher alcohol intake and older age were associated with lower odds of ULT initiation but were not associated with flares. ULT was initiated in 27.7% (95%CI 27.3-28.0%): 5.7% (95%CI 5.5-5.9%) within 12 months of diagnosis. ULT initiation rates were higher in patients with recurrent flares., Conclusion: Approximately one in six people with incident gout had a second flare within 12 months. Factors associated with flare recurrence and ULT initiation were similar, but ULT initiation occurred later after diagnosis than previously thought., (© 2023. The Author(s).)

Objective: To investigate the onset of comorbidities and pattern of flares over 5 years according to baseline comorbidity clusters in people with gout., Methods: In a prospective primary care-based cohort study, adults aged ≥18 years with gout were identified from primary care medical records in 20 general practices across the West Midlands, UK and followed up over 5 years. Four clusters of participants have been defined previously according to baseline comorbidity status. The associations of (i) incident comorbidities and (ii) gout flares with baseline cluster membership were estimated using age and sex-adjusted Poisson regression and mixed effects ordinal logistic regression, respectively., Results: The comorbidity with the highest incidence was coronary artery disease (39.2%), followed by hypertension (36.7%), chronic kidney disease stage ≥3 (18.1%), obesity (16.0%), hyperlipidaemia (11.7%), diabetes (8.8%) and cancer (8.4%). There were statistically significant associations observed between cluster membership and incidence of coronary artery disease, hyperlipidaemia, heart failure and hypertension. In each cluster, nearly one-third of participants reported two or more gout flares at each time-point. History of oligo/polyarticular flares (odds ratio [OR]= 2.16, 95% confidence interval [CI]: 1.73, 2.70) and obesity (1.66, 95% CI: 1.21, 2.25) were associated with increasing flares whereas current use of allopurinol was associated with lower risk (0.42, 95% CI: 0.34-0.53). Cluster membership was not associated with flares., Conclusion: Substantial numbers of people in each cluster developed new comorbidities that varies by cluster membership. People also experienced multiple flares over time, but these did not differ between clusters. Clinicians should be vigilant for the development of new comorbidities in people with gout., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The objective of this study was to explore the clinical and microbiological outcomes associated with substituting inhaled aztreonam lysine for an intravenous antibiotic in the treatment of acute pulmonary exacerbations of CF., Methods: An open-label randomised crossover pilot trial was conducted at a UK CF centre among 16 adults with CF and P. aeruginosa infection. Median [IQR] age was 29.5 [24.5-32.5], mean ± SD forced expiratory volume in 1 second (FEV1) was 52.4 ± 14.7 % predicted. Over the course of two exacerbations, participants were randomised to sequentially receive 14 days of inhaled aztreonam lysine plus IV colistimethate (AZLI+IV), or dual IV antibiotics (IV+IV). Primary outcome was absolute change in % predicted FEV1. Other outcomes evaluated changes in quality of life, bacterial load and the lung microbiota., Results: The difference between mean change in lung function at day 14 between AZLI+IV and IV+IV was +4.6% (95% CI 2.1-7.2, p=0.002). The minimum clinically important difference of the Cystic Fibrosis Revised Questionnaire (CFQ-R) was achieved more frequently with AZLI+IV (10/12, 83.3%) than IV+IV (7/16, 43.8%), p=0.05. No differences were observed for modulation of serum white cell count, C-reactive protein or sputum bacterial load. Microbiome compositional changes were observed with IV+IV (Bray-Curtis r 2 =0.14, p=0.02), but not AZLI+IV (r 2 =0.03, p=0.64)., Conclusion: In adults with CF and P. aeruginosa infection experiencing an acute pulmonary exacerbation, AZLI+IV improved lung function and quality of life compared to the current standard treatment. These findings support the need for larger definitive trials of inhaled antibiotics in the acute setting., Clinical Trial Registration: EudraCT 2016-002832-34 ClinicalTrials.org NCT02894684., Competing Interests: Declaration of Competing Interest GY, LW, NH, MJW and JF declare no conflicts of interest. FF has received honoraria from Gilead Sciences, Vertex and Chiesi. CW has received honoraria from Chiesi. DN has received research grants from Gilead Sciences and honoraria from Gilead Sciences and Vertex., (Copyright © 2020. Published by Elsevier B.V.)

Background: As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics., Methods: A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations., Results: Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p<0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p=0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p=0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively)., Conclusions: There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety., Competing Interests: Declaration of Competing Interest Sigal Kaplan is an employee of Teva Pharmaceutical Industries Ltd. Diana Bilton has no conflicts of interest. Susan C Charman, Andrew Lee, and Noreen Caine are employees of the UKCFT, which received financial support from Teva Pharmaceuticals B.V. to conduct this study., (Copyright © 2020. Published by Elsevier B.V.)

Background: In hospitalised patients with exacerbation of Chronic Obstructive Pulmonary Disease, European and British guidelines endorse oxygen target saturations of 88%-92%, with adjustment to 94%-98% if carbon dioxide levels are normal. We assessed the impact of admission oxygen saturation level and baseline carbon dioxide on inpatient mortality., Methods: Patients were identified from the prospective Dyspnoea, Eosinopenia, Consolidation, Acidaemia and Atrial Fibrillation (DECAF) derivation study (December 2008-June 2010) and the mixed methods DECAF validation study (January 2012 to May 2014). In six UK hospitals, of 2645 patients with COPD exacerbation, 1027 patients were in receipt of supplemental oxygen at admission. All had a clinical history of COPD and obstructive spirometry. These patients were subdivided into the following groups: admission oxygen saturations of 87% or less, 88%-92%, 93%-96% or 97%-100%. Inpatient mortality was calculated for each group and expressed as ORs. The DECAF score and National Early Warning Score 2 (excluding oxygen saturation) were used in binary logistic regression to adjust for baseline risk., Results: In patients with COPD receiving supplemental oxygen, oxygen saturations above 92% were associated with higher mortality and an adverse dose-response. Compared with the 88%-92% group, the adjusted risk of death (OR) in the 93%-96% and 97%-100% groups was 1.98 (95% CI 1.09 to 3.60, p=0.025) and 2.97 (95% CI 1.58 to 5.58, p=0.001). In the subgroup with normocapnia, the mortality signal remained significant in both the 93%-96% and 97%-100% groups., Conclusions: Inpatient mortality was lowest in those with oxygen saturations of 88%-92%. Even modest elevations in oxygen saturations above this range (93%-96%) were associated with an increased risk of death. A similar mortality trend was seen in both patients with hypercapnia and normocapnia. This shows that the practice of setting different target saturations based on carbon dioxide levels is not justified. Treating all patients with COPD with target saturations of 88%-92% will simplify prescribing and should improve outcome., Trial Registration Number: UKCRN ID 14214., Competing Interests: Competing interests: All authors declare: JS has no conflicts of interest to declare. CE reports grants from National Institute of Health Research, outside of the submitted work. SB reports grants from National Institute of Health Research, Philips Respironics and from Pfizer Open Air, personal fees from Pfizer, AstraZeneca, and ResMed, and non-financial support from Boehringer Ingelheim and GlaxoSmithKline outside the submitted work. No author has financial relationships with any organisation that might have an interest in the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma., Methods: We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000-31 December 2016) retrospective cohort of reproductive-age (16-45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition., Results: The 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3-4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use., Conclusions: Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required., Protocol Registration Number: European Union electronic Register of Post-Authorisation Studies (EUPAS22967)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Cough is an important symptom of asthma. The objective assessment of chronic cough has been enhanced by the development of ambulatory cough monitoring systems. Mepolizumab has been demonstrated to reduce exacerbations in eosinophilic asthmatics long-term. We evaluate the utility of objective cough count as an outcome measure in severe eosinophilic asthma treated with mepolizumab. Consecutive, consenting patients initiated on treatment with mepolizumab had a 24-h cough count recorded at baseline; this was repeated at 1, 3 and 6 months. Asthma control questionnaire (ACQ) scores and exacerbation frequency were also recorded. The mean 24-h cough count in 11 subjects (8 females, mean age 53.6 years) was 172.4 at baseline; at 1, 3 and 6 months following initiation of treatment this decreased to 101.4, 92 and 70.8, respectively (p < 0.02). Significant improvements were also observed in mean ACQ score (3-1.6, p < 0.01) and exacerbation frequency (5.5 per year - 1.3, p < 0.01). Objective cough measurement could be used as an early, precise and clinically relevant endpoint in assessing response to asthma therapy.

Study Design: Retrospective chart audit., Objectives: The National Early Warning Score (NEWS) is based on seven physiological parameters which can be altered in some individuals with spinal cord injuries (SCI). The aim was to start the development of adapted NEWS suitable for SCI population. The objective was to determine the SBP NEWS specificity based on neurological level of injury (NLI) and completeness of injury., Setting: Tertiary centre in the UK., Methods: Adult patients admitted for the first time to the National Spinal Injuries Centre between 1 January 2015 and 31 December 2016 were included if they were >6 months post injury. Data were extracted retrospectively including the last ten consecutive BP and heart rate readings before discharge. Data were analysed based on different AIS grades, completeness of injury and NLI., Results: One hundred and ninety one patients were admitted in 2015 and 2016 and 142 patients were included in the primary analysis. The mean SBP ranged between 92 and 151 mmHg. Patients with the NLI of T6 and above (≥T6) motor complete lesions had a significantly lower SBP than motor incomplete lesions. The specificity of the SBP NEWS was 35.3% in ≥T6 motor complete individuals versus 80.3% in ≥T6 motor incomplete individuals., Conclusion: The baseline BP is significantly lower in the ≥T6 motor complete SCI individuals (>6 months post injury) resulting in a very low specificity of 35.3% to SBP NEWS, which could lead to mismatch between clinical deterioration and NEWS resulting in lack of timely clinical response.

Background: Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β 2 -agonist and long-acting muscarinic antagonist)., Methods: In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution., Results: Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included. Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL. Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year. In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability. Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases., Conclusion: A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions. A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.

Some researches with different designs investigated the seasonal pattern of psoriasis; however, the seasonal variation in public interest in psoriasis has not yet been examined. The monitoring of internet search activity has increasingly been used to gain insights into public interest in health-related topics. The aim of the investigation is to employ the Google Trends datasets to evaluate whether a seasonal trend exists in the internet searches of psoriasis by the general public. In the observational investigation, the Google Trends was queried for the [psoriasis] in the United States, the United Kingdom, Canada, Ireland, Australia, and New Zealand between January 2004 and December 2018. The cosinor analysis demonstrated a statistically significant seasonal pattern of searches for [psoriasis] in the United Kingdom (p < 0.001), Canada (p = 0.002), Ireland (p < 0.001), Australia (p < 0.001), and New Zealand (p < 0.001), and a trend towards a seasonal variation in searches in the United States (p = 0.079), with the zenith in late winter/early spring and through in late summer/early fall. A zenith in late winter/early spring and valley in late summer/early fall presented an approximately 6-month difference between hemispheres. Public interest in seeking psoriasis information through internet searches displayed a seasonal pattern, with the highest interest in the late winter/early spring. If a more comprehensive study validated the association of psoriasis flares with patterns in online searches, beyond investigating only seasonality in public interest, the internet data could be used to guide public health interventions and to manage the care of patients with psoriasis.

Background: The impact of smoking at diagnosis and subsequent smoking cessation on clinical outcomes in Crohn's disease (CD) has not been evaluated in a population-based cohort., Methods: Using a nationally representative clinical research database, we identified incident cases of CD between 2005 and 2014. We compared the following outcomes: overall corticosteroid (CS) use; flares requiring CS; CS dependency and intestinal surgery between smokers and non-smokers at time of CD diagnosis. Differences in these outcomes were also compared between persistent smokers and smokers who quit within 2 years of diagnosis., Results: We identified 3553 patients with a new CD diagnosis over the study period of whom 1121 (32%) were smokers. Smokers at CD diagnosis had significantly higher CS-use (56 versus 47%, p < 0.0001), proportionally more CS flares (>1 CS flare/year: 9 versus 6%, p < 0.0001), and higher CS dependency (27 versus 21%, p < 0.0001) than non-smokers. Regression analysis identified smoking at diagnosis to be associated with a higher risk of intestinal surgery (HR 1.64, 95% CI 1.16-2.52). There was a significantly higher proportion of 'quitters' who remained steroid-free through follow-up in comparison to 'persistent smokers' (45.4 versus 37.5%, respectively, p = 0.02). 'Quitters' also had lower rates of CS dependency compared to 'persistent smokers' (24 versus 33%, p = 0.008)., Conclusions: Smokers at CD diagnosis have higher CS-use, CS dependency and higher risk of intestinal surgery. Quitting smoking appears to have beneficial effects on disease related outcomes, including reducing CS dependency highlighting the importance of offering early smoking cessation support.