Diane Bunn

Risk and predictors of infection leading to hospitalisation in a large primary-care-derived cohort of patients with inflammatory polyarthritis

Background: The increased mortality observed in patients with rheumatoid arthritis is partly due to an increased occurrence of serious infections. A retrospective study from the Mayo Clinic found that infection risk is increased in rheumatoid arthritis. In particular, serious infection was associated with severe disease and use of corticosteroids. Robust estimates are required from prospective studies of incident cases. Objective: To examine the risk of infection leading to hospitalisation and potential factors associated with this risk in an unselected population of patients with inflammatory polyarthritis. Design: A prospective cohort study comparing infection incidence in new-onset patients with inflammatory polyarthritis with local population experience. Patients and methods: 2108 patients with inflammatory polyarthritis from a community-based register were studied and followed up annually (median 9.2 years). The rate of hospitalisations for serious infection was compared with the rate of hospitalisations in the regional population. The contribution of potential predictors was assessed by undertaking a within-cohort analysis. Results: Overall, the incidence of infection was more than two and a half times that of the general population (varying by site). History of smoking, corticosteroid use and rheumatoid factor were found to be significantly independent predictors of infection-related hospitalisation. Patients with inflammatory polyarthritis with all three factors were more than seven times as likely to be hospitalised compared with the rest of the cohort. Discussion: These findings provide background data on the risk of infection associated with rheumatoid arthritis, and are of particular interest given the current awareness of the risk of infection associated with anti-tumour necrosis factorα treatments.

The performance of anti–cyclic citrullinated peptide antibodies in predicting the severity of radiologic damage in inflammatory polyarthritis: Results from the Norfolk Arthritis Register

Objective Anti–cyclic citrullinated peptide (anti-CCP) antibodies are a stronger predictor of the severity of rheumatoid arthritis than is rheumatoid factor (RF). Their role in predicting outcome in unselected patients with new-onset inflammatory polyarthritis (IP) has not been examined. The aims of this study were to examine the role of baseline RF and anti-CCP antibodies in determining the likelihood of patients having erosions at presentation or in predicting future radiologic damage, and to determine whether anti-CCP antibodies or RF is sufficiently robust to be clinically useful in guiding treatment decisions in early IP. Methods Patients were recruited from the Norfolk Arthritis Register. Logistic regression models were fitted to test the ability of anti-CCP antibodies and RF to predict erosions. Further models were investigated to examine the role of anti-CCP antibodies in patients stratified by RF status. Results The presence of anti-CCP antibodies at baseline was strongly associated with both prevalent erosions (odds ratio [OR] 2.53 [95% confidence interval (95% CI) 1.48–4.30]) and developing erosions at 5 years (OR 10.2 [95% CI 6.2–16.9]). These ORs were higher than those for RF (OR 1.63 [95% CI 0.94–2.82] and OR 3.4 [95% CI 2.2–5.2], respectively). The likelihood ratio (LR) for the prediction of prevalent erosions and erosions at 5 years was highest in the RF−subgroup (LR 2.2 and 5.8, respectively). However, 27% of anti-CCP−patients had developed erosions by 5 years. Conclusion Despite their strong association with the presence, development, and extent of erosions, anti-CCP antibodies alone are not a sufficiently accurate measure upon which to base clinical treatment decisions. Knowledge of anti-CCP antibody status is most informative in RF−negative patients.

Early functional disability predicts both all-cause and cardiovascular mortality in people with inflammatory polyarthritis: results from the Norfolk Arthritis Register

Objective: To investigate the predictive value of early functional disability in patients with inflammatory polyarthritis (IP), for all-cause and cardiovascular disease (CVD) mortality. Methods: 1010 subjects with new-onset IP from the Norfolk Arthritis Register were studied. All were seen at baseline and at 1 year. Health Assessment Questionnaire (HAQ) scores were obtained at both time points. Vital status at 10 years from registration was established through central records. Mortality (all-cause and CVD) per 1000 person-years were calculated by HAQ stratum (HAQ scores <1, 1–2 and ⩾2). The predictive value of HAQ (per unit increase) at the two time points, adjusted for age at onset of symptom, sex and other factors found to predict mortality, was assessed using Cox regression models. The analysis was repeated for those who satisfied the 1987 American College of Rheumatology criteria for rheumatoid arthritis (RA) by 5 years. Results: By 10 years, 171 (16.9%) subjects had died. 89 deaths (52%) were attributed to CVD. Mortality was greatest in the highest HAQ group at both time points. Following adjustment for other predictors, HAQ score at year 1 remained a significant predictor of all-cause mortality (HR 1.46; 95% CI 1.15 to 1.85) and CVD mortality (HR 1.49; 95% CI 1.12 to 1.97). The predictive value of HAQ at year 1 was similar in the RA subgroup. Conclusions: Our data show that at 1 year of follow-up, HAQ score is an important independent predictor of subsequent all-cause and CVD mortalities in people with IP and RA. Baseline HAQ scores are of less value.

Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis

Purpose: Methotrexate (MTX) is the first choice conventional disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It is not universally effective, however; although to date it is not possible to predict with any accuracy which patients will respond to treatment. The aim of this analysis was to examine whether clinical and genetic variables could be used to predict response to MTX. Methods: Patients recruited to the Norfolk Arthritis Register (NOAR), a primary care based inception cohort of patients with inflammatory polyarthritis, were eligible for this analysis if they were commenced on MTX as their first DMARD within 3 months of their baseline visit and had at least 2 years of follow-up data. Outcome on MTX was defined as: (1) stopped for adverse events; (2) stopped for inefficacy or second DMARD added; (3) stopped for other reasons; or (4) remained on MTX monotherapy. Multiple logistic regression was used to establish which variables (including demographics, disease activity and Health Assessment Questionnaire score) predicted stopping monotherapy for inefficacy or adverse event (with those remaining on treatment taken as the referent category). The area under the Receiver Operating Characteristic curves (AUC ROC), were used to determine how accurate the model was at predicting outcome. Results: 309 patients were included in this analysis. At 1 year (2 years), 34 (46) patients had stopped for adverse events and 25 (49) had either stopped monotherapy for inefficacy or had a second DMARD added. 231 (188) patients remained on MTX monotherapy. The strongest predictor of inefficacy at both time points was shared epitope positivity: odds ratios (OR) 5.8 (95% confidence intervals (CI) 1.3 to 25.6) at 1 year, OR 3.0 (95% CI 1.3 to 7.3) at 2 years. High Health Assessment Questionnaire score (OR 1.84 95% CI 1.12 to 3.01) and female gender (OR 2.2, 95% CI 0.92 to 5.28) were associated with adverse events on MTX at 1 year. However, even the most optimal combinations of the factors analysed were only weakly predictive of treatment outcome: AUC ROC for adverse events 0.68 (95% CI 0.58 to 0.78) and for inefficacy AUC ROC 0.71 (95% CI 0.6 to 0.81). Conclusions: Within this cohort, routine clinical and laboratory factors were poor at predicting outcome of treatment with MTX. Given the major therapeutic advantage to be derived from accurate prediction of treatment outcome, further studies will need to investigate novel biological and other markers.

Water-loss dehydration and aging ☆

This review defines water-loss and salt-loss dehydration. For older people serum osmolality appears the most appropriate gold standard for diagnosis of water-loss dehydration, but clear signs of early dehydration have not been developed. In older adults, lower muscle mass, reduced kidney function, physical and cognitive disabilities, blunted thirst, and polypharmacy all increase dehydration risk. Cross-sectional studies suggest a water-loss dehydration prevalence of 20-30% in this population. Water-loss dehydration is associated with higher mortality, morbidity and disability in older people, but evidence is still needed that this relationship is causal. There are a variety of ways we may be able to help older people reduce their risk of dehydration by recognising that they are not drinking enough, and being helped to drink more. Strategies to increase fluid intake in residential care homes include identifying and overcoming individual and institutional barriers to drinking, such as being worried about not reaching the toilet in time, physical inability to make or to reach drinks, and reduced social drinking and drinking pleasure. Research needs are discussed, some of which will be addressed by the FP7-funded NU-AGE (New dietary strategies addressing the specific needs of elderly population for a healthy ageing in Europe) trial.

The influence of age at symptom onset and length of followup on mortality in patients with recent-onset inflammatory polyarthritis

Objective To investigate the influence of age at symptom onset and length of followup on mortality in patients with recent-onset inflammatory polyarthritis (IP), and to examine predictors of mortality in relation to disease duration. Methods From 1990 to 1994, patients with recent-onset IP were registered with the Norfolk Arthritis Register (NOAR) and followed up prospectively. Standardized mortality ratios (SMRs) were calculated for all-cause and cardiovascular disease (CVD) mortality and for those who were younger than age 55 years at disease onset and for the first 5 and 10 years of followup. Cox proportional hazards models were developed to assess predictors of early and later mortality. Results Of 1,098 patients, 224 (20%) had died by the end of 2004. All-cause and CVD mortality were increased in rheumatoid factor (RF)–positive patients and in this subgroup, CVD mortality was increased at both early and later followup (SMR 5-year followup 1.93 [95% confidence interval 1.08–3.19]; SMR 10-year followup 2.00 [95% confidence interval 1.37–2.80]). CVD mortality was highest in seropositive patients <55 years of age at disease onset (SMR 5.58 [95% confidence interval 2.24–11.50]). In multivariate models, age at onset, male sex, RF positivity, Health Assessment Questionnaire score ≥1.5, and nodules were predictors of early and later mortality. Conclusion Patients with IP had higher rates of CVD mortality throughout the followup period studied, and this was highest in seropositive patients who were <55 years of age at symptom onset. This subgroup deserves particular attention in terms of disease and risk factor modification. Nodules were independent predictors of CVD mortality, suggesting that extraarticular/vascular inflammation identifies patients at particularly high CVD risk.

Effectiveness of interventions to improve, maintain or facilitate oral food and/or drink intake in people with dementia: systematic review

© 2014 Abdelhamid et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Using lifestyle factors to identify individuals at higher risk of inflammatory polyarthritis (results from the European Prospective Investigation of Cancer-Norfolk and the Norfolk Arthritis Register—the EPIC-2-NOAR Study)

Objectives To investigate the association of lifestyle factors with risk of inflammatory polyarthritis (IP) and rheumatoid arthritis (RA). Methods The European Prospective Investigation of Cancer, Norfolk, UK (EPIC-Norfolk) gathered lifestyle data from participants aged 40–79 years from 1993 to 1997. Individuals who subsequently developed IP were identified by linkage with the Norfolk Arthritis Register. A Cox proportional hazard model was developed, and a score assigned to each risk factor to calculate the odds of developing IP. Results 25 455 EPIC participants were followed for a median (IQR) of 14.2 (12.9, 15.3) years; 184 developed incident IP (138 cumulatively fulfilled criteria for RA; 107 were seropositive). Pack-years of smoking were associated with increased risk of IP and RA in men (HR 1.21 (95% CI 1.08 to 1.37) per 10-pack-years) and seropositive IP (HR 1.24 (95% CI 1.10 to 1.41)) for all. Diabetes mellitus was associated with increased risk of IP (HR 2.54 (95% CI 1.26 to 5.09)), while alcohol (HR 0.86 (95% CI 0.74 to 0.99) per unit/day) and higher social class (HR 0.36 (95% CI 0.15 to 0.89) for professionals vs manual workers) were associated with reduced risk. Body mass index was associated with seronegative IP (HR 2.75 (95% CI 1.39 to 5.46) for obese vs normal-weight participants). In women, parity (HR 2.81 (95% CI 1.37 to 5.76) for ≥2 vs no children) was associated with increased risk, and breast feeding (HR 0.66 (95% CI 0.46 to 0.94) for every 52 weeks of breast feeding) was inversely associated with risk. Risk factors from the model were used to generate a ‘risk score’. A total of 1159 (8.4%) women had scores reflecting a >3-fold increased risk of IP over those with a score of 0. Conclusions Several easily ascertained clinical and lifestyle factors can be used to stratify populations for risk of IP.

Increasing Fluid Intake and Reducing Dehydration Risk in Older People Living in Long-Term Care: A Systematic Review

OBJECTIVE To assess the efficacy of interventions and environmental factors on increasing fluid intake or reducing dehydration risk in older people living in long-term care facilities. DESIGN Systematic review of intervention and observational studies. DATA SOURCES Thirteen electronic databases were searched from inception until September 2013 in all languages. References of included papers and reviews were checked. ELIGIBILITY CRITERIA Intervention and observational studies investigating modifiable factors to increase fluid intake and/or reduce dehydration risk in older people (≥65 years) living in long-term care facilities who could drink orally. REVIEW METHODS Two reviewers independently screened, selected, abstracted data, and assessed risk of bias from included studies; narrative synthesis was performed. RESULTS A total of 4328 titles and abstracts were identified, 325 full-text articles were obtained and 23 were included in the review. Nineteen intervention and 4 observational studies from 7 countries investigated factors at the resident, institutional, or policy level. Overall, the studies were at high risk of bias due to selection and attrition bias and lack of valid outcome measures of fluid intake and dehydration assessment. Reported findings from 6 of the 9 intervention studies investigating the effect of multicomponent strategies on fluid intake or dehydration described a positive effect. Components included greater choice and availability of beverages, increased staff awareness, and increased staff assistance with drinking and toileting. Implementation of the US Resident Assessment Instrument reduced dehydration prevalence from 3% to 1%, P = .01. Two smaller studies reported positive effects: one on fluid intake in 9 men with Alzheimer disease using high-contrast red cups, the other involved supplementing 13 mildly dehydrated residents with oral hydration solution over 5 days to reduce dehydration. Modifications to the dining environment, advice to residents, presentation of beverages, and mode of delivery (straw vs beaker; prethickened drinks vs those thickened at the bedside) were inconclusive. Two large observational studies with good internal validity investigated effects of ownership; in Canada, for-profit ownership was associated with increased hospital admissions for dehydration; no difference was seen in dehydration prevalence between US for-profit and not-for-profit homes, although chain facilities were associated with lower odds of dehydration. This US study did not suggest any effect of staffing levels on dehydration prevalence. CONCLUSIONS A wide range of interventions and exposures were identified, but the efficacy of many strategies remains unproven due to the high risk of bias present in many studies. Reducing dehydration prevalence in long-term care facilities is likely to require multiple strategies involving policymakers, management, and care staff, but these require further investigation using more robust study methodologies. The review protocol was registered with the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42012003100).

The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosive disease in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register

Objectives. Recent whole-genome and candidate gene association studies in RA have identified a number of single nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. It remains poorly understood how recently identified genetic factors may contribute to RA severity. We therefore sought to investigate the role of recently identified RA susceptibility SNP markers in predicting erosive outcome in patients with recent-onset inflammatory polyarthritis (IP). Methods. DNA and X-ray data were available for 1049 patients who were registered between 1990 and 2003 with the Norfolk Arthritis Register (NOAR); a primary care-based inception cohort of patients with recent-onset IP. Demographic and clinical data were recorded at inclusion, and at yearly assessments thereafter. Patients were genotyped for 18 SNP markers. The presence of serum anti citrullinated peptide antibodies (ACPAs) was assessed in samples collected at inclusion to the NOAR. The association of serological and genetic markers with poor radiological (Larsen) score at Years 1 and 5, and erosions at Years 1 and 5 was investigated. Results. Baseline ACPA positivity was associated with erosive disease and higher radiological damage. SNP markers within the TRAF1/C5 locus were associated with erosive disease at Year 1 [rs2900180: odds ratio (OR) 1.53 (95% CI 1.14, 2.05)] and Year 5 [rs2900180: OR 1.47 (95% CI 1.07, 2.02)]. None of the SNP markers tested was associated with Larsen score. Conclusion. Our results are in keeping with a previous report and suggest that the TRAF1/C5 region is associated with risk of development of radiological erosions in IP/RA patients. The finding requires replication in other large data sets.