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Physical and mental illnesses are driven by ethnicity, social, environmental and economic determinants. Novel theoretical frameworks in rheumatoid arthritis (RA) focus on links and adverse interactions between and within biological and social factors. This review aimed to summarise associations between socioeconomic status (SES) and RA disease activity, and implications for future research. Articles studying the association between SES and RA disease activity were identified, from 1946 until March 2021. The research question was: Is there an association between social deprivation and disease activity in people with RA? Articles meeting inclusion criteria were examined by one author, with 10% screened at abstract and full paper stage by a second author. Disagreements were resolved with input from a third reviewer. Information was extracted on definition/measure of SES, ethnicity, education, employment, comorbidities, disease activity and presence/absence of association between SES and disease activity. Initially, 1750 articles were identified, with 30 articles ultimately included. SES definition varied markedly—10 articles used a formal scale and most used educational attainment as a proxy. Most studies controlled for lifestyle factors including smoking and body mass index, and comorbidities. Twenty-five articles concluded an association between SES and RA disease activity; two were unclear; three found no association. We have demonstrated the association between low SES and worse RA outcomes. There is a need for further research into the mechanisms underpinning this, including application of mixed-methods methodology and consideration of syndemic frameworks to understand bio–bio and bio–social interactions, to examine disease drivers and outcomes holistically.

Current literature addressing the pharmacological principles guiding glucocorticoid (GC) administration in ARDS is scant. This paucity of information may have led to the heterogeneity of treatment protocols and misinterpretation of available findings. GCs are agonist compounds that bind to the GC receptor (GR) producing a pharmacological response. Clinical efficacy depends on the magnitude and duration of exposure to GR. We updated the meta-analysis of randomized trials investigating GC treatment in ARDS, focusing on treatment protocols and response. We synthesized the current literature on the role of the GR in GC therapy including genomic and non-genomic effects, and integrated current clinical pharmacology knowledge of various GCs, including hydrocortisone, methylprednisolone and dexamethasone. This review addresses the role dosage, timing of initiation, mode of administration, duration, and tapering play in achieving optimal response to GC therapy in ARDS. Based on RCTs’ findings, GC plasma concentration–time profiles, and pharmacodynamic studies, optimal results are most likely achievable with early intervention, an initial bolus dose to achieve close to maximal GRα saturation, followed by a continuous infusion to maintain high levels of response throughout the treatment period. In addition, patients receiving similar GC doses may experience substantial between-patient variability in plasma concentrations affecting clinical response. GC should be dose-adjusted and administered for a duration targeting clinical and laboratory improvement, followed by dose-tapering to achieve gradual recovery of the suppressed hypothalamic–pituitary–adrenal (HPA) axis. These findings have practical clinical relevance. Future RCTs should consider these pharmacological principles in the study design and interpretation of findings. Electronic supplementary material The online version of this article (10.1007/s00134-020-06289-8) contains supplementary material, which is available to authorized users.

Objectives Evidence suggests that factors beyond disease activity associate with functional disability in RA. The primary study objective was to explore associations between comorbidities, sociodemographic factors and functional outcomes at five and 10 years. Methods RA patients from two UK prospective cohorts were grouped into low ( Results In total, 2701 RA patients were recruited (mean age 56.1 years, 66.9% female). A total of 1718 (63.4%) had five-year and 820 (30.4%) 10-year follow-up data. In multivariable analysis, no association was found between RDCI and HAQ ≥ 1.5 at five or 10 years. Sociodemographic factors (increased age at disease onset, female gender, minority ethnicity) were associated with higher odds of HAQ ≥ 1.5 at five and 10 years, with worse deprivation additionally associated with HAQ ≥ 1.5 at 10 years (OR 0.79, 95% CI: 0.69, 0.90). Conclusion Comorbidities at baseline have not been found to be associated with worse RA functional outcome in the long-term. On the other hand, sociodemographic factors, independently of disease measures, are associated with worse functional outcome in RA at five and 10 years, in models adjusting for comorbidity burden. Tailoring management interventions according to not only clinical disease parameters but also patient sociodemographic factors may improve long-term outcomes including functional disability.

This systematic literature review aimed to analyse terms describing coexisting conditions in the RA literature, informing the need for an operationalized definition of multimorbidity. Articles discussing RA with multimorbidity, published 1946 until August 2020, were identified. The primary outcome was the use and/or definition of ‘multimorbidity’ in RA. Information extracted included terms defining coexisting conditions, the use of a comorbidity/multimorbidity score and the use of ‘index disease’ to describe RA (more applicable to comorbidity than multimorbidity). Thirty-nine articles were included. Eight articles used the term ‘multimorbidity’, 18 used ‘comorbidity’ and 12 used both terms, 7 synonymously. One used no term. Fourteen articles fully defined the term. The number of co-existing conditions described in included studies was one-121. Twelve articles used a comorbidity/multimorbidity score. Four articles described RA as the ‘index disease’. Our results demonstrate inconsistent use of the term multimorbidity. Improved assessment of multimorbidity is indicated in RA patients, including an operationalized use and definition.

Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3 ml/min/1.73 m2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice-weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost, maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Health care cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. Ninety-two percent of incremental and 75% of standard arm patients had a urea clearance of 2 ml/min/1.73 m2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly lower compared to standard hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.

Background Rheumatoid arthritis interstitial lung disease (RA-ILD) is a rare but significant manifestation of RA, with high mortality. Methotrexate (MTX) is known to cause hypersensitivity pneumonitis, but its effect on the onset of RA-ILD is less clear. Objectives To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early RA inception cohorts with a focus on MTX exposure. Methods Patients with new diagnosis of RA recruited to the early RA study (ERAS) and the early RA network (ERAN). Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3- 6 months, at 12 months and annually for up to 25 years thereafter. Primary outcome was the association of MTX exposure with incident RA-ILD. Secondary outcomes were the association of demographic, comorbid and RA specific factors on incident RA-ILD using univariate and multivariate analyses and the association of MTX exposure on time to RA-ILD diagnosis using time to event Cox proportional hazards analysis. Results Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of incident RA-ILD cases only developing after any csDMARD treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (O.R. 0.85 CI 0.49, 1.49 p=0.578) and a non-significant trend for delayed ILD diagnosis (O.R. 0.54 CI 0.28, 1.06 p=0.072) (see Figure). In an extended analysis including all RA-ILD cases (n=92, including those present pre csDMARD exposure), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (O.R. 0.48, CI 0.3, 0.79 p=0.004) and longer time to ILD diagnosis (O.R. 0.41, CI 0.23, 0.75 p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first out-patient visit (see Table). Conclusion In ERAS/ERAN, incident RA-ILD is significantly associated with older age of RA onset, ever smoking, nodules, RF positivity, male gender, ESR, and a longer time from first RA symptoms to first secondary care visit. There is no association between MTX treatment and incident RA-ILD. MTX may have a protective role in delaying the onset of RA-ILD. Acknowledgement All recruiting ERAS and ERAN centers Disclosure of Interests Patrick KIELY Paid instructor for: Amgen, Gilead, BMS, Speakers bureau: Abbvie, BMS, UCB, Lilly, Pfizer, Amanda Busby: None declared, Elena Nikiphorou: None declared, Keith Sullivan: None declared, Adam Young: None declared

ObjectivesTo assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure.DesignMulticentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN).SettingSecondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland.ParticipantsPatients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3–6 months, at 12 months and annually thereafter.Primary and secondary outcome measuresPrimary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis.ResultsOf 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit.ConclusionsMTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD.

Initiating twice-weekly haemodialysis (2×HD) in patients who retain significant residual kidney function (RKF) may have benefits. We aimed to determine differences between patients initiated on twice- and thrice-weekly regimes, with respect to loss of kidney function, survival and other safety parameters.We conducted a single-centre retrospective study of patients initiating dialysis with a residual urea clearance (KRU) of ≥3 mL/min, over a 20-year period. Patients who had 2×HD for ≥3 months during the 12 months following initiation of 2×HD were identified for comparison with those dialysed thrice-weekly (3×HD).The 2×HD group consisted of 154 patients, and the 3×HD group 411 patients. The 2×HD patients were younger (59 ± 15 versus 62 ± 15 years: P = 0.014) and weighed less (70 ± 16 versus 80 ± 18 kg: P 0.001). More were females (34% versus 27%: P = 0.004). Fewer had diabetes (25% versus 34%: P = 0.04) and peripheral vascular disease (PVD) (13% versus 23%: P = 0.008). Baseline KRU was similar in both groups (5.3 ± 2.4 for 2 × HD versus 5.1 ± 2.8 mL/min for 3 × HD: P = 0.507). In a mixed effects model correcting for between-group differences in comorbidities and demographics, 3×HD was associated with increased rate of loss of KRU and separation of KRU. In separate mixed effects models, group (2×HD versus 3×HD) was not associated with differences in serum potassium or phosphate, and the groups did not differ with respect to total standard Kt/V. Survival, adjusted for age, gender, weight, baseline KRU and comorbidity (prevalence of diabetes, cardiac disease, PVD and malignancy) was greater in the 2×HD group (hazard ratio 0.755: P = 0.044). In sub-analyses, the survival benefit was confined to women, and those of less than median bodyweight.2×HD initiation as part of an incremental programme with regular monthly monitoring of KRU was safe and associated with a reduced rate of loss of RKF early after dialysis initiation and improved survival. Randomized controlled trials of this approach are indicated.

© 2018 The Author(s). This an open access work distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.