Pain in rheumatoid arthritis: a seven-year follow-up study of pain distribution and factors associated with transition from and to chronic widespread pain.

OBJECTIVE: To study transitions from and to chronic widespread pain (CWP) over 7 years in patients with rheumatoid arthritis (RA). METHOD: Two postal questionnaires were sent to patients included in the BARFOT (Better Anti-Rheumatic Pharmacotherapy) study, the first in 2010 and the second in 2017. The questionnaires assessed pain, number of tender and swollen joints, functional disability, health-related quality of life (HRQoL), pharmacological treatment, lifestyle factors, and patient-reported body mass index (BMI). The responders to both questionnaires were divided into three groups according to the reported pain duration and distribution: patients having no chronic pain (NCP), chronic regional pain (CRP), and CWP. RESULTS: In all, 953 patients answered the questionnaires at both time-points. One-third (324) of the patients reported CWP in 2010, and 140 (43%) of the patients had transition to NCP or CRP in 2017. In multivariate logistic regression models, adjusting for age, gender, and disease duration, transition from CWP was associated with normal BMI, fewer tender joints, less pain, less fatigue, fewer pain regions, less disability, better HRQoL, and biologic treatment. In 2010, 628 patients reported NCP or CRP, whereas 114 of them reported CWP in 2017. Transition to CWP was associated with female gender, obesity, more tender and swollen joints, higher pain-related variables, worse disability, and worse HRQoL. CONCLUSION: There are modifiable factors associated with transitions from and to CWP that could be identified. Paying attention to these factors could improve pain treatment in the management of RA.

Unacceptable pain in the BARFOT inception cohort of patients with rheumatoid arthritis: a long-term study.

Objectives: Pain is the most common and troublesome complaint in rheumatoid arthritis (RA). This study aimed to assess the prevalence and clinical implications of unacceptable pain in an inception cohort of patients with RA. Method: This study followed 477 patients from the BARFOT (Better Anti-Rheumatic FarmacOTherapy) early RA cohort for 15 years. Unacceptable pain was defined as ≥ 40 mm on a visual analogue scale for pain, while tolerable pain denoted no pain or pain below this cut-off, according to the patient acceptable symptom state concept. Results: Unacceptable pain was frequent. At the 15 year follow-up visit, 34% had unacceptable pain. Patients with unacceptable pain had, compared with patients with tolerable pain, significantly more disease activity, worse patient global assessment, and worse function on the Health Assessment Questionnaire and Signals of Functional Impairment, but the degree of joint destruction was similar. Disease-modifying anti-rheumatic drug treatment was similar, but patients with unacceptable pain were more often treated with corticosteroids. At 15 years, patients with unacceptable pain who were in remission (33%) had less inflammation and better function than those not in remission, suggesting the presence of non-inflammatory causes of pain. Conclusions: In this cohort of patients with RA, pain was frequent and severe, with negative effects on experienced health and function. Unacceptable pain was frequent and occurred also in patients in remission, indicating that pain in RA is multifactorial and should always be regarded as an important concern in itself. The cause of pain should be recognized and treated appropriately.

Screening for breast cancer-related lymphoedema: self-assessment of symptoms and signs.

INTRODUCTION: In the absence of monitoring programs, those at risk of developing breast cancer-related lymphoedema (BCRL) must detect its development. However, the efficacy of self-assessment for BCRL has not been widely investigated. This study will determine if symptoms and signs of BCRL are associated with lymphoedema detected by bioimpedance spectroscopy (BIS) and whether those with and without BCRL can accurately assess the signs of its presence. METHODS AND RESULTS: Participants with a history of breast cancer (n = 100) reported the presence/absence of symptoms associated with upper limb BCRL and underwent assessment for pitting oedema and differences in tissue texture between their arms (pinch). BIS detected BCRL in 48 women. Women were more likely to have BIS-detected BCRL if they reported swelling (odds ratio (OR), 58.8; 95% CI, 4.9 to 709.4; p = 0.001) or had inter-limb tissue texture differences in their forearm (OR, 73.5; 95% CI, 7.3 to 736.9; p = < 0.001) or upper arm (OR, 23.9; 95% CI, 2.8 to 201.7; p = 0.003). Agreement between therapist and self-assessment of signs of BCRL was almost perfect (kappa, 0.819 to 0.940). A combination of self-reported swelling and/or self-assessed forearm tissue texture difference identified all cases of BIS-detected BCRL. CONCLUSION: Participants accurately identified the presence or absence of physical signs of BCRL in their arm. Perceived swelling and differences in tissue texture in the affected arm were associated with, and sensitive to, BIS-detected BCRL. These findings support the use of self-assessment to determine if BCRL is developing, indicating the need for professional assessment.

Repair of bone erosions in rheumatoid arthritis: a systematic literature review.

Objective: The aim of this study was to review the literature to identify studies reporting repair of erosions in rheumatoid arthritis (RA).Method: A systematic literature search for publications on the repair of erosions was performed in PubMed and Embase, limited to human adults and published in English. Titles, abstracts, and full reports of articles identified were screened by the first author and verified by the second author.Results: The search yielded 411 publications, of which 33 (20 articles and 13 case reports) suggested repair of erosions in RA. There was heterogeneity in study design and different definitions of repair were used. Twelve articles showed strong evidence of repair, in eight articles repair was probable, and in all 13 case reports repair was evident.Conclusion: Repair of erosions does occur in RA. The definition and frequency of repair vary and the possible clinical relevance is unclear, motivating further studies.

The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor.

OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies are reported to associate with more radiographic progression within the total rheumatoid arthritis (RA) population and anti-citrullinated peptide antibody (ACPA)-negative subgroup. We explored the association of anti-CarP with radiographic progression in RA and aimed to replicate the association and evaluate the added value of anti-CarP antibodies in relation to ACPA and rheumatoid factor (RF). METHODS: 576 Swedish and 628 Dutch patients with RA (2394 and 3247 sets of radiographs, respectively) were longitudinally studied. Replication was restricted to the Swedish patients. In both cohorts, the association of anti-CarP with radiographic progression was determined in strata of patients with similar ACPA and RF status; results of both cohorts were combined in fixed-effect meta-analyses. The net percentage of patients for whom the radiographic progression in 5 years was additionally correctly classified when adding anti-CarP to a model including ACPA and RF was evaluated. RESULTS: Anti-CarP associated with radiographic progression in the total Swedish RA population (beta=1.11 per year, p=8.75×10-13) and in the ACPA-negative subgroup (beta=1.14 per year, p=0.034). Anti-CarP associated with more radiographic progression in the strata of ACPA-positive/RF-negative, ACPA-negative/RF-positive and ACPA-positive/RF-positive patients with RA (respective p values 0.014, 0.019 and 0.0056). A model including ACPA and RF correctly classified 54% and 57% of the patients; adding anti-CarP to this model did not increase these percentages (54% and 56% were correctly classified). CONCLUSIONS: Anti-CarP antibodies associated with more severe radiographic progression in the total and ACPA-negative RA population. Anti-CarP-positivity had a statistically significant additive value to ACPA and RF, but did not improve correct classification of patients.

Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present.

OBJECTIVES: In rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA. METHODS: Autoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression. RESULTS: In both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies. CONCLUSIONS: The number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype.

Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts.

OBJECTIVE: Patients with rheumatoid arthritis (RA)-related autoantibodies have an increased mortality rate. Different autoantibodies are frequently co-occurring and it is unclear which autoantibodies associate with increased mortality. In addition, association with different causes of death is thus far unexplored. Both questions were addressed in three early RA populations. METHODS: 2331 patients with early RA included in Better Anti-Rheumatic Farmaco-Therapy cohort (BARFOT) (n=805), Norfolk Arthritis Register (NOAR) (n=678) and Leiden Early Arthritis Clinic cohort (EAC) (n=848) were studied. The presence of anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF) and anticarbamylated protein (anti-CarP) antibodies was studied in relation to all-cause and cause-specific mortality, obtained from national death registers. Cox proportional hazards regression models (adjusted for age, sex, smoking and inclusion year) were constructed per cohort; data were combined in inverse-weighted meta-analyses. RESULTS: During 26 300 person-years of observation, 29% of BARFOT patients, 30% of NOAR and 18% of EAC patients died, corresponding to mortality rates of 24.9, 21.0 and 20.8 per 1000 person-years. The HR for all-cause mortality (95% CI) was 1.48 (1.22 to 1.79) for ACPA, 1.47 (1.22 to 1.78) for RF and 1.33 (1.11 to 1.60) for anti-CarP. When including all three antibodies in one model, RF was associated with all-cause mortality independent of other autoantibodies, HR 1.30 (1.04 to 1.63). When subsequently stratifying for death cause, ACPA positivity associated with increased cardiovascular death, HR 1.52 (1.04 to 2.21), and RF with increased neoplasm-related death, HR 1.64 (1.02 to 2.62), and respiratory disease-related death, HR 1.71 (1.01 to 2.88). CONCLUSIONS: The presence of RF in patients with RA associates with an increased overall mortality rate. Cause-specific mortality rates differed between autoantibodies: ACPA associates with increased cardiovascular death and RF with death related to neoplasm and respiratory disease.

MRI evidence of persistent joint inflammation and progressive joint damage despite clinical remission during treatment of early rheumatoid arthritis.

OBJECTIVES: To determine the value of magnetic resonance imaging (MRI) of bones and joints in patients with recent-onset rheumatoid arthritis (RA) treated for 2 years from diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids. METHOD: Thirteen patients with early RA were treated according to clinical practice and followed with MRI, radiographs, and Disease Activity Score calculated on 28 joints (DAS28) at inclusion (baseline) and after 1, 4, 7, 13, and 25 months. MRI of the dominant wrist and metacarpophalangeal (MCP) joints were assessed for synovitis, bone oedema, and erosions using the RA MRI Score (RAMRIS) and for tenosynovitis by an MRI tenosynovitis scoring method. Radiographs were assessed by the van der Heijde modified Sharp score (SHS). Clinical remission was defined by a DAS28 < 2.6. RESULTS: MRI at baseline detected inflammation in joints and tendons in all patients as well as erosions in 10 out of 13 patients. Over time, the erosion score increased while the synovitis and tenosynovitis scores remained almost unchanged. Bone oedema strongly correlated with synovitis. Synovitis and tenosynovitis correlated well with the erosion score at baseline but not thereafter. The MRI changes showed that joint damage started early and continued in the presence of persistent synovial and tenosynovial inflammation. CONCLUSIONS: The observations made in this small study suggest that the treatment goal of 'clinical remission' should be supplemented by a 'joint remission' goal. To this end, MRI is an appropriate tool. Further studies are needed to evaluate the optimal use of MRI in early RA.

Persistently active disease is common in patients with rheumatoid arthritis, particularly in women: a long-term inception cohort study.

OBJECTIVES: Despite improved treatment strategies for rheumatoid arthritis (RA), some patients do not respond satisfactorily. The aim of this study was to investigate the course and outcome of early RA diagnosed during the 1990s and followed for 8 years with a focus on those who did not respond well to treatment. METHOD: This study included 640 patients (66% women) who were enrolled in the BARFOT (Better Anti-Rheumatic PharmacOTherapy) RA inception cohort between the years 1993 and 1999. The 28-joint count Disease Activity Score (DAS28) < 2.6 criteria were used to assess remission. Persistent disease (PD) was defined as absence of remission at all predefined follow-up visits at 1, 2, 5, and 8 years. Function was assessed by Health Assessment Questionnaire (HAQ) and Signals of Functional Impairment (SOFI) scores and radiological joint damage by the Sharp/van der Heijde score (SHS). RESULTS: Of the 640 patients, 214 (37%) had PD (43% of the women and 25% of the men). Over the 8 years of follow-up, patients with PD had significantly worse mean values for patient's global health measured on a visual analogue scale (VAS patGH), VAS pain, HAQ, SOFI, and SHS compared with those in the non-PD group. Multivariate logistic regression analyses revealed that female gender, current smoking, disease activity at baseline, and absence of remission at 6 months independently predicted PD. CONCLUSIONS: Of the patients who entered the early RA inception cohort, 37% suffered a PD course over 8 years. The consequences of PD with regard to general health, pain, function, and joint damage were considerable. Of note, PD was more common in women than in men.

Changes in attitudes, intended behaviour, and mental health literacy in the Swedish population 2009-2014: an evaluation of a national antistigma programme.

OBJECTIVE: Public stigma of mental illness is still a major problem where numerous population studies during the last decade have mainly shown no improvements. A Swedish national antistigma campaign has been running 2010-2014. The aim of this study was to investigate changes in public stigma during this period as compared to baseline in 2009. METHODS: Yearly population surveys were made between 2009 and 2014 including assessments of mental health literacy, attitudes, and intended future behaviour. Two surveys were made, one including a nationally representative sample and one including a representative sample from three original campaign regions. Multiple regression analyses, also including age, gender, education, and familiarity with mental illness were made to investigate yearly changes in public stigma compared to baseline. RESULTS: Mental health literacy improved significantly in the campaign regions between 2009 and 2014, as did intended future behaviour. Attitudes toward mental illness also improved significantly. Improvements were also shown in the national population surveys, but the time pattern of these compared to that of the original campaign regions indicated that these changes took place mainly after the campaign had been extended to a further five Swedish regions. CONCLUSION: The results of our surveys suggest that a campaign primarily based on social contact theory and involving people with lived experience of mental illness may, even in a rather short-term perspective, have a significant positive impact on mental health literacy, attitudes, and intentions of social contact with people with mental illness.

Smoking as a risk factor for the radiological severity of rheumatoid arthritis: a study on six cohorts.

BACKGROUND: Smoking is a risk factor for the development of anti -citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA). Whether smoking predisposes to severe joint damage progression is not known, since deleterious, protective and neutral observations have been made. OBJECTIVE: To determine the effect of smoking on joint damage progression. METHODS: Smoking status was assessed in 3158 RA patients included in six cohorts (Leiden Early Arthritis Clinic (Leiden-EAC), BARFOT, Lund, Iceland, NDB and Wichita). In total 9412 radiographs were assessed. Multivariate normal regression and linear regression analyses were performed. Data were summarised in a random effects inverse variance meta-analysis. RESULTS: When comparing radiological progression for RA patients that were never, past and current smokers, smoking was significantly associated with more severe joint damage in Leiden-EAC (p=0.042) and BARFOT (p=0.015) RA patients. No significant associations were found in the other cohorts, though a meta-analysis on the six cohorts showed significantly more severe joint damage progression in smokers (p=0.01). Since smoking predisposes to ACPA, analyses were repeated with ACPA as additional adjustment factor. Then the association was lost (meta-analysis p=0.29). CONCLUSIONS: This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.

Hydrogen induced optically-active defects in silicon photonic nanocavities.

We demonstrate intense room temperature photoluminescence (PL) from optically active hydrogen- related defects incorporated into crystalline silicon. Hydrogen was incorporated into the device layer of a silicon on insulator (SOI) wafer by two methods: hydrogen plasma treatment and ion implantation. The room temperature PL spectra show two broad PL bands centered at 1300 and 1500 nm wavelengths: the first one relates to implanted defects while the other band mainly relates to the plasma treatment. Structural characterization reveals the presence of nanometric platelets and bubbles and we attribute different features of the emission spectrum to the presence of these different kind of defects. The emission is further enhanced by introducing defects into photonic crystal (PhC) nanocavities. Transmission electron microscopy analyses revealed that the isotropicity of plasma treatment causes the formation of a higher defects density around the whole cavity compared to the ion implantation technique, while ion implantation creates a lower density of defects embedded in the Si layer, resulting in a higher PL enhancement. These results further increase the understanding of the nature of optically active hydrogen defects and their relation with the observed photoluminescence, which will ultimately lead to the development of intense and tunable crystalline silicon light sources at room temperature.

Impurity sublattice localization in ZnO revealed by Li marker diffusion.

Sublattice localization of impurities in compound semiconductors, e.g., ZnO, determines their electronic and optical action. Despite that the impurity position may be envisaged based on charge considerations, the actual localization is often unknown, limiting our understanding of the incorporation and possible doping mechanisms. In this study, we demonstrate that the preferential sublattice occupation for a number of impurities in ZnO can be revealed by monitoring Li diffusion. In particular, using ion implantation, the impurity incorporation into the Zn sublattice (holds for, B, Mg, P, Ag, Cd, and Sb) manifests in the formation of Li-depleted regions behind the implanted one, while Li pileups in the region of the implantation peaks for impurities residing on O sites, e.g., N. The behavior appears to be of general validity and the phenomena are explained in terms of the apparent surplus of Zn and O interstitials, related to the lattice localization of the impurities. Furthermore, Cd+O and Mg+O co-doping experiments revealed that implanted O atoms act as an efficient blocking "filter" for fast diffusing Zn interstitials.

Exploring risk for abuse of children with chronic conditions or disabilities--parent's perceptions of stressors and the role of professionals.

BACKGROUND: Children with chronic conditions or disabilities are at an increased risk for abuse. High level of parental stress has been identified as possible trigger for abuse, were a combination of several factors are of importance, as lack of social support and limited resources in the neighbourhood. Suggestions for preventive measures have merely focused on parenting strategies and targeted intervention programmes. So far, little attention has been paid on how the risk for abuse might relate to parent's perceptions of stressors and the role of professionals. The purpose of the current study was therefore to explore risk factors for abuse with focus on both parent-child and parent-professional relationships. METHOD: Semi-structured in-depth interviews with 15 parents of children with chronic conditions or disability were collected and analysed according to qualitative content analysis. FINDINGS: Three major themes were found that could be seen as risk factors for child abuse: (1) Emotional demands in precarious situations between parent and child. (2) Gradual shift in responsibility from professionals to parents concerning access to and co-ordination of service and support. (3) Emotionally closed environment between professionals and parents and taboo on talking about abuse. The gradual shift in responsibility had emotional implications, which could reinforce parental stress and thereby also indirect increase the risk of child abuse. The gradual shift in responsibility also seemed to generate an emotionally closed environment and reinforce the taboo on talking about abuse, which in turn hindered preventive measures. CONCLUSIONS: In the light of parent's perceptions of stressors and the role of professionals the findings indicate that abuse against children with chronic conditions or disability is not only a family matter, but also depending on qualities in service, professional support and social norms. The result pinpoints three challenges for preventive measures, all with emotional implications, parental strategies, organizational efforts and cultural awareness.

Reliance on prey-derived nitrogen by the carnivorous plant Drosera rotundifolia decreases with increasing nitrogen deposition.

• Carnivory in plants is presumed to be an adaptation to a low-nutrient environment. Nitrogen (N) from carnivory is expected to become a less important component of the N budget as root N availability increases. • Here, we investigated the uptake of N via roots versus prey of the carnivorous plant Drosera rotundifolia growing in ombrotrophic bogs along a latitudinal N deposition gradient through Sweden, using a natural abundance stable isotope mass balance technique. • Drosera rotundifolia plants receiving the lowest level of N deposition obtained a greater proportion of N from prey (57%) than did plants on bogs with higher N deposition (22% at intermediate and 33% at the highest deposition). When adjusted for differences in plant mass, this pattern was also present when considering total prey N uptake (66, 26 and 26 µg prey N per plant at the low, intermediate and high N deposition sites, respectively). The pattern of mass-adjusted root N uptake was opposite to this (47, 75 and 86 µg N per plant). • Drosera rotundifolia plants in this study switched from reliance on prey N to reliance on root-derived N as a result of increasing N availability from atmospheric N deposition.

Negative-U system of carbon vacancy in 4H-SiC.

Using electron paramagnetic resonance (EPR), energy levels of the carbon vacancy (V(C)) in 4H-SiC and its negative-U properties have been determined. Combining EPR and deep-level transient spectroscopy we show that the two most common defects in as-grown 4H-SiC--the Z(1/2) lifetime-limiting defect and the EH(7) deep defect--are related to the double acceptor (2-|0) and single donor (0|+) levels of V(C), respectively.

Smoking at onset of rheumatoid arthritis (RA) and its effect on disease activity and functional status: experiences from BARFOT, a long-term observational study on early RA.

OBJECTIVES: To assess the effects of smoking on disease outcome in a large cohort of patients with early rheumatoid arthritis (RA). METHODS: Between 1996 and 2004, 1787 adult patients (disease duration ≤ 1 year) were included in the BARFOT early RA study in Sweden. Smoking status was recorded at inclusion in the study. Disease Activity Score using 28 joint counts (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ) score, rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (anti-CCP), general health (GH) and pain visual analogue scales (VAS), and drug treatment were registered at inclusion and at follow-up at 3, 6, and 12 months. European League Against Rheumatism (EULAR) response and remission criteria were applied at 3, 6, and 12 months. RESULTS: The proportion of patients who smoked at inclusion in the study fell from 29% in 1996 to 20% in 2004. There were no significant differences in disease activity at inclusion stratified according to smoking status. At 12 months of follow-up, 18% of current smokers at inclusion, 12% of previous smokers, and 11% of never smokers had high disease activity (DAS28 > 5.1, p = 0.005). Significantly fewer current smokers were in remission at 12 months (33%) compared to never smokers (36%) and previous smokers (42%) (p = 0.013). Current smoking at inclusion independently predicted poor EULAR response up to 12 months of follow-up. CONCLUSION: The present study gives some support to earlier data indicating that RA patients who smoke have a more active disease but further studies are needed to confirm this.

Effects on joint destruction and remission, bone turnover and lack of influence on atherogenesis: a review of the BARFOT low-dose prednisolone studies on patients with early RA.

As early as in 1948 a woman with severe rheumatoid arthritis (RA) was successfully treated with glucocorticoids. However, not until recently has the role of GCs in the treatment of RA been clarified and supported by scientific evidence in a limited number of randomised studies. The present article reviews four reports from the BARFOT (Better Anti-Rheumatic FarmacOTherapy) low-dose prednisolone study based on 250 patients with early RA. These patients were randomised to have either DMARDs only or DMARDs plus prednisolone 7.5 mg daily for two years. It was shown that low-dose prednisolone in addition to a DMARD was superior to DMARDs alone in the ability to inhibit joint damage and induce clinical remission. A follow-up study demonstrated that remission after 2 years with low-dose prednisolone was associated with reduced joint destruction also after 4 years. Prednisolone had no or minor effects on bone density and the frequency of adverse effects was small. A third article measuring markers of bone synthesis and resorption demonstrated that the suppressive effect on bone synthesis exerted by prednisolone was counteracted by the ability of prednisolone to hamper the inflammatory mediated increase in bone resorption. In a fourth article assessing intima-media thickness and endothelial function, no influence of prednisolone 7.5 mg daily on atherosclerosis was observed. Altogether, these four studies provide evidence for recommending low-dose prednisolone treatment in combination with DMARDs for at least two years to patients with recent onset RA.

The feasibility of trace element supplementation for stable operation of wheat stillage-fed biogas tank reactors.

The aim of this study was to investigate the effect of trace element supplementation on operation of wheat stillage-fed biogas tank reactors. The stillage used was a residue from bio-ethanol production, containing high levels of sulfate. In biogas production, high sulfate content has been associated with poor process stability in terms of low methane production and accumulation of process intermediates. However, the results of the present study show that this problem can be overcome by trace element supplementations. Four lab-scale wheat stillage-fed biogas tank reactors were operated for 345 days at a hydraulic retention time of 20 days (37 degrees C). It was concluded that daily supplementation with Co (0.5 mg L(-1)), Ni (0.2 mg L(-1)) and Fe (0.5 g L(-1)) were required for maintaining process stability at the organic loading rate of 4.0 g volatile solids L(-1) day(-1).