International development of a patient-centered core outcome set for assessing health-related quality of life in metastatic breast cancer patients.

PURPOSE: For patients living with metastatic breast cancer (MBC), achieving best possible health-related quality of life, along with maximizing survival, is vital. Yet, we have no systemic way to determine if we achieve these goals. A Core Outcome Set (COS) that allows standardized measurement of outcomes important to patients, but also promotes discussing these outcomes during clinical encounters, is long overdue. METHODS: An international expert group (EG) of patient advocates, researchers, medical specialists, nurse specialists, and pharmaceutical industry representatives (n = 17) reviewed a list of relevant outcomes retrieved from the literature. A broader group (n = 141: patients/patient advocates (n = 45), health care professionals/researchers (n = 64), pharmaceutical industry representatives (n = 28), and health authority representatives (n = 4)) participated in a modified Delphi procedure, scoring the relevance of outcomes in two survey rounds. The EG finalized the COS in a consensus meeting. RESULTS: The final MBC COS includes 101 variables about: (1) health-related quality of life (HRQoL, n = 26) and adverse events (n = 24); (2) baseline patient characteristics (n = 9); and (3) clinical variables (n = 42). Many outcome that cover aspects of HRQoL relevant to MBC patients are included, e.g. daily functioning (including ability to work), psychosocial/emotional functioning, sexual functioning, and relationship with the medical team. CONCLUSION: The COS developed in this study contains important administrative data, clinical records, and clinician-reported measures that captures the impact of cancer. The COS is important for standardization of clinical research and implementation in daily practice and has received accreditation by the International Consortium for Health Outcomes Measurement (ICHOM).

Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites.

BACKGROUND: Increasing evidence has sparked a debate on the loss of sensitivity of scabies mites to conventional permethrin therapy. Mutations in the voltage-sensitive sodium channels (VSSC) were associated with knockdown resistance (kdr) in many arthropods, but have never been identified in Sarcoptes scabiei variatio (var.) hominis mites. OBJECTIVES: To identify factors contributing to therapy failure. METHODS: Sixty-seven mites were collected from 64 scabies-infested patients in Vienna, Austria, of whom 85.9% were refractory to prior permethrin-based treatments, and genotyped for the presence of nucleotide polymorphisms in Domain II of the VSSC, known to be associated with kdr. Information regarding previous antiscabietic therapies, decontamination procedures and possible re-infestations by contacts as well as the response to re-imposed therapies were obtained. RESULTS: Sequence alignment comparisons revealed previously unidentified mutations in the coding region of Domain II of the VSSC. A novel A1663T transversion was detected in 97.0% of the mites, resulting in a non-synonymous substitution from methionine to leucine, M918L, a mutation known to confer kdr in other arthropods. In addition, a synonymous G1659A transition was identified in one mite, which otherwise showed a nucleotide sequence identical to the wild-type reference. No major inconsistencies were observed within the previous therapeutic and decontamination procedures, which could have accounted for the observed non-responsiveness to permethrin-based therapies. Subsequent cure of infestation was achieved in 65.6% of the participants, predominantly by combination therapies with topical permethrin and systemic ivermectin. However, in 14.6% of the cured cases, permethrin monotherapy sufficed for eradication of scabies, albeit in some cases prolonged exposure was necessary. CONCLUSIONS: The kdr-associated M918L mutation in the VSSC gene has now emerged in S. scabiei var. hominis mites. Hence, loss of sensitivity to permethrin due to kdr-type resistance may be more prevalent than anticipated and may be decisive for the therapy responsiveness of scabies-infested patients.

[Lay version of the 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis : Translation into German and linguistic validation in German-speaking countries with people affected]. / Die laienverständliche Version der 2018 EULAR Empfehlungen zu körperlicher Aktivität von Menschen mit entzündlich-rheumatischen und degenerativen Erkrankungen : Übersetzung ins Deutsche und sprachliche Validierung im deutschsprachigen Raum mit Betroffenen.

BACKGROUND: Physical activity and exercise are beneficial for people with rheumatic diseases; however, recommendations for the management of rheumatoid arthritis (RA), spondyloarthritis (SpA) and hip- and knee osteoarthritis (HOA/KOA) are usually unspecific with respect to mode and dose of exercise. This is why the 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis were formulated. The recommendations consist of 4 overarching principles and 10 recommendations. These were also published as a lay version in the English language. AIM: Translation of the lay version into German and its linguistic validation in Austria, Germany and Switzerland. METHODS: A professional translation was reviewed by the authors, including people with, RA, SpA, HOA/KOA from the three German-speaking countries, which provided a prefinal lay version. Subsequently, eight interviews with people with RA, SpA, HOA/KOA were conducted in each country to evaluate understandability, wording, completeness and feasibility of the prefinal lay version. Finally, the authors, i.e. those with RA, SpA, and osteoarthritis, anonymously rated their agreement to the final lay version on a 0-10 scale. RESULTS: The professional translation was substantially revised by the authors and based on the interviews. Formulations were adapted to increase readability and understandability and specify statements. Comments that would have changed content or structure were not considered. Average agreement with the particular recommendations was between 10 (SD 0) and 7.6 (SD 1.67). DISCUSSION: For people with RA/SpA/HOA/KOA the EULAR physical activity recommendations should be available in their mother language. The final German lay version is valid and accepted across all three German-speaking countries. Thus, the physical activity recommendations can be provided to people with rheumatic diseases in an understandable and feasible way.

RECOMMENDATIONS FOR USE AND SCORING OF ORAL HEALTH IMPACT PROFILE VERSIONS.

BACKGROUND: OHIP's original seven-domain structure does not fit empirical data, but a psychometrically sound and clinically more plausible structure with the four OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact has emerged. Consequently, use and scoring of available OHIP versions need to be revisited. AIM: We assessed how well the overall construct OHRQoL and its four dimensions were measured with several OHIP versions (20, 19, 14, and 5 items) to derive recommendations which instruments should be used and how to score them. METHODS: Data came from the "Dimensions of OHRQoL Project" and used the project's learning sample (5,173 prosthodontic patients and general population subjects with 49-item OHIP data). We computed correlations among OHIP versions' summary scores. Correlations between OHRQoL dimensions, on one hand, and OHIP versions' domain scores or OHIP-5's items, on the other hand, were also computed. OHIP use and scoring recommendations were derived for psychometrically solid but also practical OHRQoL assessment. RESULTS: Summary scores of 5-, 14-, 19- and 49-item versions correlated highly (r = 0.91-0.98), suggesting similar OHRQoL construct measurement across versions. The OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact were best measured by the OHIP domain scores for Physical Disability, Physical Pain, Psychological Discomfort, and Handicap, respectively. CONCLUSION: Recommendations were derived which OHIP should be preferably used and how OHIP versions should be scored to capture the overall construct and the dimensions of OHRQoL. Psychometrically solid and practical OHRQoL assessment in all settings across all oral health conditions can be achieved with the 5-item OHIP.

Increased risk of death associated with the use of proton-pump inhibitors in patients with dementia and controls - a pharmacoepidemiological claims data analysis.

BACKGROUND AND PURPOSE: The use of proton-pump inhibitors (PPIs) was reported to be associated with increased mortality risk and has been proposed as a potential risk factor for neurodegenerative diseases. We aimed to assess the impact of PPI use on survival in patients with dementia as compared with controls. METHODS: This register-based control-matched cohort study included 28 428 patients with dementia ascertained by the prescription of antidementia drugs and two control individuals matched by sex, age and area of residence for each patient with dementia during the study period from 1 January 2005 to 30 June 2016. Cumulative defined daily doses (DDDs) of PPIs were extracted from the health insurance prescription registries. A multivariate Cox regression model for non-proportional hazards was used to analyse mortality risk in dependence of PPI exposure, which was limited to 1 year preceding the date of cohort entry (index date) in order to avoid immortal time bias. RESULTS: The PPI exposure of 100 DDDs in the year before the index date was associated with an increased mortality risk in patients with dementia (adjusted hazard ratio, 1.07; 95% confidence intervals, 1.03-1.12), but also in controls (adjusted hazard ratio, 1.47; 95% confidence intervals, 1.31-1.64). The mortality risk in relation to PPI use was significantly lower in patients with dementia as compared with controls (P < 0.0001) and highest in the first 2 years after the index date in both cohorts. CONCLUSIONS: Our findings promote more stringent pharmacovigilance strategies to avoid PPI use in cases lacking a clear indication for therapy or where potential risks outweigh the benefits.

Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence.

Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [18F]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction. CLINICAL TRIAL REGISTRATION: NCT01679145.

[Psychotherapy for people with bipolar disorders : An overview of evidence-based procedures and new developments]. / Psychotherapie für Menschen mit bipolaren Störungen : Übersicht über evidenzbasierte Verfahren und neuere Entwicklungen.

Many individual studies and meta-analyses have shown that psychotherapeutic interventions for people with bipolar disorders can positively influence the course of the disease. This article gives an overview of the development of psychotherapy for people with bipolar disorders. According to the current guidelines the evidence-based procedures with their mechanisms of action are presented and new developments in psychotherapy research in this field are outlined.

Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.

Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of supraphysiologic thyroid hormone improves depressive symptoms in patients with bipolar disorder by modulating function in components of the anterior limbic network.

[Healthcare models for traumatized refugees in Germany]. / Versorgungsmodelle für traumatisierte Flüchtlinge in Deutschland.

People with a migration background are a risk group for psychiatric disorders. Innovative, transnational and sustainable projects are necessary to ensure adequate care for refugees and asylum seekers. Selected projects of the University of Munich, the Charité Berlin and the University of Konstanz show promising approaches in addition to other initiatives.

Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

BACKGROUND: Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. METHOD: During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. RESULTS: BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. CONCLUSIONS: This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

Characterizing the concept of activity pacing as a non-pharmacological intervention in rheumatology care: results of an international Delphi survey.

OBJECTIVE: To develop a consensual list of the most important aspects of activity pacing (AP) as an intervention within the context of non-pharmacological rheumatology care. METHOD: An international, multidisciplinary expert panel comprising 60 clinicians and/or healthcare providers experienced in AP across 12 different countries participated in a Delphi survey. Over four Delphi rounds, the panel identified and ranked the most important goals of AP, behaviours of AP (the actions people take to meet the goal of AP), strategies to change behaviour in AP, and contextual factors that should be acknowledged when instructing AP. Additionally, topics for future research on AP were formulated and prioritized. RESULTS: The Delphi panel prioritized 9 goals, 11 behaviours, 9 strategies to change behaviour, and 10 contextual factors of AP. These items were integrated into a consensual list containing the most important aspects of AP interventions in non-pharmacological rheumatology care. Nine topics for future research on AP with the highest ranking were included in a research agenda highlighting that future research should focus on the effectiveness of AP interventions and on appropriate outcome measures to assess its effectiveness, as selected by 64% and 82% of the panellists, respectively. CONCLUSIONS: The diversity and number of items included in the consensual list developed in the current study reflect the heterogeneity of the concept of AP. This study is an important first step in achieving more transparency and homogeneity in the concept of AP in both rheumatology daily clinical practice and research.

Prediction of antidepressant response to venlafaxine by a combination of early response assessment and therapeutic drug monitoring.

INTRODUCTION: Early assessment of a therapeutic response is a central goal in antidepressant treatment. The present study examined the potential for therapeutic drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient response and remission). METHODS: 88 patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric ratings were measured for up to 6 weeks by independent study raters. RESULTS: An early improvement was significantly more common in venlafaxine responders than non-responders (χ(2); p=0.007). While ODV serum levels were significantly higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early response combined with an ODV serum level above the median of 222 ng/mL were significantly more likely to achieve full response (binary logistic model; p<0.01). Sensitivity (84% for early response) and specificity (81% for combination of early response and therapeutic drug monitoring) were sufficient to qualify as a reasonable screening instrument. CONCLUSION: Our results indicate that early improvement and ODV serum concentration are predictive of therapeutic outcome and can thus be used to guide use of the antidepressant venlafaxine.

Influence of levothyroxine in augmentation therapy for bipolar depression on central serotonergic function.

INTRODUCTION: Adjunctive treatment with supraphysiological doses of levothyroxine (L-T4) in bipolar depression shows promise, but the neurobiological mechanisms underlying clinical improvement are unknown. It has been postulated from animal studies that exogenous thyroid hormones may exert their modulatory effects in patients with affective disorders via an increase in serotonergic neurotransmission. Therefore, we investigated the loudness dependence of auditory evoked potentials (LDAEP) as a measure of central serotonergic activity and response to L-T4. METHODS: This 6-week, double-blind, randomized, placebo-controlled study assessed the efficacy of L-T4 adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication in 20 patients with bipolar depression. LDAEP was assessed before and after treatment with L-T4. RESULTS: Scores of the Hamilton Depression Rating Scale and Montgomery Asberg Depression Rating Scale decreased significantly during the study. There was no difference in pre- and post-treatment LDAEP between the groups, and no correlation between LDAEP and psychometric measures in the course of the study. DISCUSSION: The hypothesis of a relationship between response of augmentation therapy with levothyroxine in bipolar depression and serotonergic activity could not be confirmed.

Defining oligometastatic pancreatic cancer: a systematic review and critical synthesis of consensus.

BACKGROUND: Small retrospective series suggest that local consolidative treatment (LCT) may improve survival in oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, no uniform definition of oligometastatic disease (OMD) in PDAC exists; this impedes meaningful conclusions. PATIENTS AND METHODS: A systematic literature search using PubMed, Web of Science, and Cochrane CENTRAL registries for studies and protocols reporting on definitions and/or LCT of OMD in PDAC was performed. The primary endpoint was the definition of OMD. Levels of agreement were categorized as consensus (≥75% agreement between studies), fair agreement (50%-74%), and absent/poor agreement (<50%). RESULTS: After screening of 5374 abstracts, the full text of 218 studies was assessed, of which 76 were included in the qualitative synthesis. The majority of studies were retrospective (n = 66, 87%), two were prospective studies and eight were study protocols. Studies investigated mostly liver (n = 38, 51%) and lung metastases (n = 15, 20%). Across studies, less than one-half (n = 32, 42%) reported a definition of OMD, while 44 (58%) did not. Involvement was limited to a single organ (consensus). Additional criteria for defining OMD were the number of lesions (consensus), metastatic site (poor agreement), metastatic size (poor agreement), treatment possibilities (poor agreement), and biomarker response (poor agreement). Liver OMD could involve three or fewer lesions (consensus) and synchronous disease (fair agreement), while lung metastases could involve two or fewer lesions and metachronous disease (consensus). The large majority of studies were at a high risk of bias or did not include any control groups. CONCLUSION: Definitions of OMD were not used or varied widely between studies hampering across-study comparability and highlighting an unmet need for a consensus. The present study is part of a multistep process that aims to develop an interdisciplinary consensus on OMD in pancreatic cancer.

Autoantibody profiling in patients with very early rheumatoid arthritis: a follow-up study.

OBJECTIVE: To investigate time courses of autoantibody profiles in patients with early arthritis. PATIENTS AND METHODS: A total of 200 patients with very early arthritis (<3 months duration), among them 102 patients with a final diagnosis of rheumatoid arthritis (RA) and 98 with other rheumatic diseases, were followed up for several years. First follow-up testing was performed in all patients (mean 5 months from baseline), and 82 patients with RA and 35 patients without RA were available for last follow-up testing (mean 32 months from baseline). IgM-rheumatoid factor (RF) was measured by nephelometry, IgA-RF, IgG-RF and anti-cyclic citrullinated peptide antibodies (ACPA) by ELISA, and anti-RA33 antibodies were determined by immunoblotting. RESULTS: At baseline, IgA-RF was detectable in 29% and IgG-RF in 14% of patients with RA while IgM-RF>50 IU/ml (RF50) was positive in 45% of the patients; specificities were 97%, 99% and 96%, respectively. However, the vast majority of patients positive for IgA-RF or IgG-RF were also positive for RF50 or ACPA. During follow-up, the prevalence of ACPA slightly increased while prevalence of all RF subtypes and anti-RA33 decreased. Remarkably, the number of patients positive for RF50 and/or ACPA remained constant, and these patients had a highly increased risk for developing erosive disease in contrast to patients solely positive for anti-RA33. CONCLUSIONS: Testing for RF subtypes did not provide additional diagnostic information. Patients positive for RF50 and/or ACPA had an unfavourable prognosis, irrespectively of changes in the antibody profile during follow-up, whereas anti-RA33 positivity was inversely associated with erosiveness at baseline and at later time points.

[Health-related quality of life (HRQoL) in rheumatoid arthritis]. / Health-Related Quality of Life (HRQoL) bei rheumatoiderArthritis.

In order to measure therapeutic effects or assess disease course, outcomes measurement parameters are commonly used in patients with rheumatoid arthritis. From the patient's perspective, possibly the most important outcome measurement parameter is quality of life (QoL). QoL may be defined in terms of "health status" and "functioning in daily life". According to the WHO, quality of life is defined as the satisfaction of a patient/person with their situation in terms of health status and their ability to function in daily life. Since assessing QoL makes sense only from the patient's perspective, generic or disease-specific questionnaires are usually used. For rheumatoid arthritis, multiple questionnaires which can be used in a routine clinical setting are available. In addition, QoL is a highly subjective concept and can depend on a variety of individual factors. Thus, measurement of QoL using the profiles and indices of common instruments cannot fully account for an individual's perspective.

[Epidemiological baseline situation before the construction of a small dam in five villages of Bouaké, central Côte-d'Ivoire]. / Situation épidémiologique avant la mise en eau du barrage hydroagricole de cinq villages de Bouaké, centre Côte-d'Ivoire

Abstract From June 2007 to June 2008, entomological, malacological and parasitological investigations were carried out in five villages in close proximity to a small dam of Raf-fierkro in Bouaké, central Côte-d'Ivoire. The objective of the study was to identify vectors and intermediate host snails of parasitic diseases related to water, and to assess the prevalence of malaria, schistosomiasis and soil-transmitted helminthiasis before dam construction. Mosquitoes were caught by human landing catches, snails were collected in water bodies, and microscopic analyses of blood, stool and urine samples were carried out. Two malaria vector species were identified:Anopheles gambiae and Anopheles funestus. The average infective rate of An. gambiae ranged between 3.1 and 4.5 %. The infective rate of An. funestus was 1 % in all sites. The entomological inoculation rate ranged between 343.1 and 427.1 infective bites per person per year (ib/p/y)for An. gambiae and between 14.6 and 40.1 ib/p/y for An. funestus. Three species of were found: Plasmodium falciparum (predominant species), Plasmodium ovale and Plasmodium malariae. There were no intermediate host snails of schistosomiasis with the exception of Biomphalaria pfeifferi,intermediate host snail of Schistosoma mansoni in Ahougui. The prevalence of urinary and intestinal schistosomiasis and soil-transmitted helminthiasis was low. Our studies revealed important transmission of malaria, with the presence of three plasmodial species, whereas schistosomiasis and soil-transmitted helminthiasis were present, but only at low frequencies.

Patient perspective of hand osteoarthritis in relation to concepts covered by instruments measuring functioning: a qualitative European multicentre study.

OBJECTIVE: To explore whether the concepts important to patients with hand osteoarthritis (OA) are covered by the most commonly used instruments measuring functioning. METHOD: A qualitative multicentre study using a focus group technique was performed in five European countries: Austria, The Netherlands, Norway, Sweden and the United Kingdom. The qualitative data analysis followed a modified form of "meaning condensation" and used the International Classification of Functioning, Disability and Health (ICF) as a theoretical framework. Finally, the concepts from the focus groups were compared with the content of the most commonly used instruments which had been identified in an earlier theoretical analysis. RESULTS: Fifty-six people (51 women, mean (SD) age 62.7 (7.9) years) with hand OA participated in this study in two focus groups per centre. 63 concepts were extracted from the focus groups. Twenty-one (33%) of the 63 concepts were covered by at least one instrument. Psychological consequences, different qualities of pain, aesthetic changes and leisure activities are important concepts from the focus groups which were not covered by the instruments. The qualitative analysis revealed detailed descriptions of pain-concerning sensations, levels and a certain relation to activity, none of which were fully represented in the instruments routinely used. CONCLUSION: It was possible to combine the concepts of the focus groups from each centre into a common qualitative analysis. The concepts important to people with hand OA are not fully represented in the most commonly used instruments.

The development of a preliminary ultrasonographic scoring system for features of hand osteoarthritis.

OBJECTIVES: Painful osteoarthritis (OA) of the hand is common and a validated ultrasound (US) scoring system would be valuable for epidemiological and therapeutic outcome studies. US is increasingly used to assess peripheral joints, though most of the US focus in rheumatic diseases has been on rheumatoid arthritis. We aimed to develop a preliminary US hand OA scoring system, initially focusing on relevant pathological features with potentially high reliability. METHODS: A group of experts in the fields of OA, US and novel tool development agreed on domains and suggested scaling of the items to be used in US hand OA scoring systems. A multi-observer reliability exercise was then performed to evaluate the draft items. RESULTS: Synovitis (grey scale and Power Doppler) and osteophytes (representing activity and damage domains) were included and evaluated as the initial components of the scoring system. All three features were evaluated for their presence/absence and if present were scored using a 1-3 scale. The reliability exercise demonstrated intra-reader kappa values of 0.444-1.0, 0.211-1.0 and 0.087-1.0 for grey scale synovitis, power Doppler and osteophytes respectively. Inter-reader reliability kappa values were 0.398, 0.327 and 0.530 grey-scale synovitis, power Doppler and osteophytes respectively. Without extensive standardisation, both intra- and inter-reader reliability were moderately good. CONCLUSIONS: The draft scoring system demonstrated substantive to almost perfect percentage exact agreement on the presence/absence of the selected OA features and moderate to substantive percentage exact agreement on semi-quantitative grading. This preliminary process provides a good basis from which to further develop an US outcome tool for hand OA that has the potential to be utilised in multicentre clinical trials.

Glucocorticoid treatment in rheumatoid arthritis: low-dose therapy does not reduce responsiveness to higher doses.

BACKGROUND: Despite low-dose gluco-corticoid (GC) treatment, many patients with rheumatoid arthritis (RA) require additional flare therapy with GC at higher doses. Since low dose GC has been suggested to confer resistance to higher doses, we aimed to assess if resistance was detectable on the clinical level in patients with active RA. METHODS: Eighty-nine patients with active RA (Disease Activity Score 28, DAS28>3.2; mean age 54.5 years, mean duration of RA 9.7 years) were consecutively enrolled into a one-week trial of a total of 250 mg prednisolone. We compared improvement of the DAS28 and the Simplified Disease Activity Index (SDAI) in groups of patients with (n=41) and without (n=48) low-dose GC at baseline (by t-test). In addition, we analyzed changes of all individual core set measures of disease activity using multivariate statistics. RESULTS: All clinical, serological and functional measures improved significantly over one week (p<0.001). Baseline RA activity of patients with and without low-dose GC was on average +/- standard deviation similar among the two groups (DAS28: 4.8+/-1.2 and 4.9+/-1.1; mean SDAI: 26.1+/-14.0 and 25.9+/-13.0, respectively), and likewise there was no difference between the two groups in the final disease activity reached, for both the DAS28 (1.4+/-1.1 vs. 1.1+/-1.0; p=0.14) and the SDAI (11.1+/-13.4 vs. 11.1+/-11.4; p=0.99). Improvement in all individual measures was also not different using a multivariate model (p=0.26). CONCLUSION: Pre-treatment with low-dose GC does not appear to portend GC resistance at least clinically, since the responsiveness to GC boosts is unaffected.