Escape to the future - a qualitative study of physicians' views on the work environment, education, and support in a digital context.

BACKGROUND: The use of remote services such as video consultations (VCs) has increased significantly in the wake of the COVID-19 pandemic. In Sweden, private healthcare providers offering VCs have grown substantially since 2016 and have been controversial. Few studies have focused on physicians' experiences providing care in this context. Our aim was to study physicians' experiences of VCs, focusing on the work environment, quality of care, and educational needs. METHODS: Twenty-two semi-structured interviews were performed with physicians working with VCs in Sweden, and analyzed through inductive content analysis. RESULTS: We identified five categories; flexibility, social work environment, impact on care and society, continuous learning and career development, and organizational support. Flexibility and accessibility were considered positive features of working digitally by giving physicians control over their time and workplace and increasing patients' timely access to healthcare. Regarding collegial contact and social activities in a digital context, the majority of the participants did not experience any significant difference compared to the physical context. Access to technical support services, educational support, and collegial support in decision-making, guidance, and consultations were described as well-functioning. Satisfied patients positively impacted the work environment, and participants felt that VCs have a positive socio-economic effect. Continuity of care was considered supported, but patients did not always prioritize this. Privacy risks were considered a challenge, as were poor development of clinical skills due to the low variation of patient cases. Working for an online healthcare provider was contributing to career advancements for junior clinicians. CONCLUSIONS: Physicians appreciate the flexibility of the digital context and seem satisfied with a work environment where they have a high level of control, but few consider this a full-time career option. The pandemic year 2020 has led to a significant increase in the implementation of VCs in traditional care systems. How this affects the work environment and continuous education needs and career development remains to be seen.

More support, knowledge and awareness are needed to prepare emergency department nurses to approach potential intimate partner violence victims.

BACKGROUND: Intimate partner violence is a global health issue. In the emergency department, patients seek help for health problems that may be related to exposure to physical, psychological or sexual violence, or controlling behaviour from a current or former partner. Of the many victims that seek care in an emergency department, few are identified, especially among those whose chief complaint is not clearly related to recent physical abuse. Not having all the facts about a patient can jeopardise patient safety and delay treatment. The aim of this study was to describe experiences of caring for adults, subjected to intimate partner violence, from an emergency nurse perspective. METHODS: A qualitative semi-structured interview study of nine emergency care specialist nurses was conducted using content analysis. FINDINGS: Two categories emerged: 'Subtle signs' and 'Not being enough'. The short encounters in emergency care do not allow for deep conversations. The informants highlighted the need for more knowledge about what and how to ask in that specific context. Some mentioned situations where the question had been avoided due to lack of time to handle the answer. The interviews revealed the importance of regular discussions to increase awareness of intimate partner violence and its prevalence among patients. CONCLUSIONS: The organisation plays an important role in putting the question about intimate partner violence on the daily agenda and giving time to emergency nurses and other professions for training and reflection.

Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis.

OBJECTIVE: Treatment with CTLA-4Ig blocks T-cell activation and is clinically effective in RA. However, it is unknown if specific CD4+ T-cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4+ T cells in patients with untreated early RA (eRA). METHODS: This study included 60 patients with untreated eRA from a larger randomized trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n = 17), anti-IL6 receptor (tocilizumab, n = 21) or anti-TNF (certolizumab-pegol, n = 22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI ≤ 2.8) at week 24. Proportions of 12 CD4+ T-cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24 weeks of treatment. RESULTS: In patients treated with CTLA-4Ig, the proportions of PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline predicted CDAI remission at week 24. CD4+ T-cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24 weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1+T follicular helper (TFh) cells. CONCLUSION: These findings indicate that circulating proportions PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.

Professionals´ readiness for change to knowledge-based palliative care at nursing homes: a qualitative follow-up study after an educational intervention.

BACKGROUND: There has been a global increase in the number of people who are dying of old age. This development implies a need for good palliative care among older persons at the end of life. Here nursing homes have an important role to play. However, the principles of palliative care have not been sufficiently applied in nursing homes, and there is a need to increase the implementation of palliative care in these settings. Therefore the project named Implementation of Knowledge-Based Palliative Care in Nursing Homes (the KUPA project, to use its Swedish acronym) was started as a contribution to filling this knowledge gap. The aim of the present study was to investigate the professionals' experiences of readiness for change to knowledge-based palliative care at nursing homes after the educational intervention within the KUPA project. METHODS: The focus group method was used to interview 39 health-care professionals with the aid of semistructured questions based on the Organizational Readiness for Change theoretical framework. Six focus groups were formed at six nursing homes in two counties in southern Sweden. The groups included different types of professionals: assistant nurses, nurses, occupational therapists, physiotherapists and social workers. The analysis was conducted with an abductive approach and included deductive and inductive content analysis. RESULTS: The analysis revealed one overarching theme: hopeful readiness for change in palliative care despite remaining barriers. The main categories were increased knowledge facilitating development, enhanced team spirit, uncertainty about future plans connected with hopeful readiness and remaining organizational barriers. CONCLUSIONS: This study adds knowledge and understanding concerning professionals' readiness for change palliative care in nursing homes and shows how ready nursing home settings undertake these changes in practice. The Organizational Readiness for Change theory proved suitable for application in nursing homes to assess the professionals' experiences and to evaluate educational interventions regardless of the organization's readiness for change. TRIAL REGISTRATION: ClinicalTrials NCT02708498 , first registration 15/03/2016.

Translation, adaptation and testing of an emergency care satisfaction scale in Swedish pediatric emergency departments.

BACKGROUND: Pediatric healthcare today shows a rising demand for research focusing on children's perspectives on and consumer satisfaction with the nursing care they receive. Therefore, the purpose of this study was to translate and adapt the Consumer Emergency Care Satisfaction Scale (CECSS), a paper-based, self-administered 19-item questionnaire originally developed in the United States and targeted towards adults, and then test the new version in Swedish pediatric emergency departments. METHODS: The study was designed with a two-phase approach. Firstly, a forward-backward translation of the CECSS, involving expert consensus, was performed, and then the questionnaire was adapted for children aged 10-18 and assessed for face and content validity. Secondly, the translated and adapted questionnaire was tested with a clinical sample for construct validity, internal consistency, and reliability. This last aspect was assessed using a structured telephone interview 7-10 days after the participant visited a pediatric emergency department. All children participating in this study gave their assent (< 15 years) or consent (≥ 15 years), and their guardian's written informed consent was also obtained. RESULTS: The paper-based, self-administered 19-item Swedish version of the CECSS was tested on a clinical sample consisting of 203 nonurgent children (boys: n = 109, 53.7 % and girls: n = 94, 46.3 %) between 10 and 18 years (mean age 13.8, SD 2.29). The factor analysis revealed three factors that explain 63.1 % of the total variation in the 15 items. The Cronbach's alphas for the three dimensions (caring, teaching, and clinical competence) varied between 0.79 and 0.88. The intraclass correlation coefficient (ICC) for the entire Swedish version of the CECSS was 0.58, and the ICCs for the three dimensions varied between 0.56 and 0.71. CONCLUSIONS: The results show that the developed Swedish Pediatric Consumer Emergency Care Satisfaction Scale (p-CECSS-S) is a valid, stable and easy-to-use-questionnaire that can be used to assess children's satisfaction with nursing care.

Significant others' perceptions of being taken seriously by the Swedish Ambulance Service when the patient is assessed as nonurgent.

BACKGROUND: At least 50% of all ambulance assignments are deemed nonurgent, while 47-96% are initiated by someone other than the patient. Previous research has highlighted the importance of being taken seriously. However, additional knowledge of how significant others experience the situation when a patient is assessed as nonurgent is needed. OBJECTIVE: The aim of this study was to explore the person-centred climate in the Ambulance Service from the perspective of significant others by means of the Person-centred Climate Questionnaire - Family version (PCQ-F), to psychometrically investigate the construct validity of additional items intended to measure perceptions of being taken seriously and to explore possible relationships between the person-centred climate and these additional items. METHODS: A retrospective, explorative, cross-sectional survey design was employed. In total, 241 questionnaires were distributed. Descriptive and comparative statistics and a factor analysis of eight items possibly constructing person-centredness are presented. RESULTS: The 100 respondents experienced the climate as very person-centred. Relationships were found between the items that might constitute person-centredness and the PCQ-F. The PCQ-F can explain perceived person-centredness through the additional items that may constitute person-centredness in the Ambulance Service context. CONCLUSION: Significant others consider eight aspects of being taken seriously as the core of person-centredness in nonurgent Ambulance Service assignments. There is a relationship between the psychosocial climate and the additional items that might constitute person-centredness.

Person-centred climate and psychometrical exploration of person-centredness and among patients not conveyed by the Ambulance Care Service.

BACKGROUND: What already is known is that as many as 50% of all Swedish Ambulance Care Service assignments are considered as non-emergency. Therefore, due to medical protocols and triage system, patients are refused conveyance to the Accident and Emergency Department by the Ambulance Care Service. AIM: The aim of this study was to psychometrically explore the construct validity of a possible dimension of person-centredness, developed from a previous published qualitative study in a nonemergency ambulance care context. A second aim was to explore patients' experiences of the person-centred climate and to explore possible relationship between it and person-centredness. DESIGN/METHODS: A retrospective, explorative, cross-sectional survey design with a convenience sample was employed. A total of 111 questionnaires were analysed using descriptive and comparative statistics. An explanatory factor analysis was also conducted. FINDINGS: A one-factor solution for the specific items possibly constructing person-centredness was found. The responses to the Person-centred Climate Questionnaire-Patient version (PCQ-P) revealed that the climate was received as highly person-centred. Relationships were found between the specific items possibly constructing person-centredness and PCQ-P. CONCLUSION: A highly valid construct of person-centredness exists within nonurgent Ambulance Care Service assignments comprising eight aspects of being taken seriously. The climate in which nonemergency ambulance care is provided has great potential to facilitate person-centredness by means of taking patients seriously. The psychosocial aspects of PCQ-P and person-centredness are somewhat related to each other.

The O-glycomap of lubricin, a novel mucin responsible for joint lubrication, identified by site-specific glycopeptide analysis.

The lubricative, heavily glycosylated mucin-like synovial glycoprotein lubricin has previously been observed to contain glycosylation changes related to rheumatoid and osteoarthritis. Thus, a site-specific investigation of the glycosylation of lubricin was undertaken, in order to further understand the pathological mechanisms involved in these diseases. Lubricin contains an serine/threonine/proline (STP)-rich domain composed of imperfect tandem repeats (EPAPTTPK), the target for O-glycosylation. In this study, using a liquid chromatography-tandem mass spectrometry approach, employing both collision-induced and electron-transfer dissociation fragmentation methods, we identified 185 O-glycopeptides within the STP-rich domain of human synovial lubricin. This showed that adjacent threonine residues within the central STP-rich region could be simultaneously and/or individually glycosylated. In addition to core 1 structures responsible for biolubrication, core 2 O-glycopeptides were also identified, indicating that lubricin glycosylation may have other roles. Investigation of the expression of polypeptide N-acetylgalactosaminyltransferase genes was carried out using cultured primary fibroblast-like synoviocytes, a cell type that expresses lubricin in vivo. This analysis showed high mRNA expression levels of the less understood polypeptide N-acetylgalactosaminyltransferase 15 and 5 in addition to the ubiquitously expressed polypeptide N-acetylgalactosaminyltransferase 1 and 2 genes. This suggests that there is a unique combination of transferase genes important for the O-glycosylation of lubricin. The site-specific glycopeptide analysis covered 82% of the protein sequence and showed that lubricin glycosylation displays both micro- and macroheterogeneity. The density of glycosylation was shown to be high: 168 sites of O-glycosylation, predominately sialylated, were identified. These glycosylation sites were focused in the central STP-rich region, giving the domain a negative charge. The more positively charged lysine and arginine residues in the N and C termini suggest that synovial lubricin exists as an amphoteric molecule. The identification of these unique properties of lubricin may provide insight into the important low-friction lubricating functions of lubricin during natural joint movement.

A room of one's own--Being cared for in a hospital with a single-bed room design.

AIM: To illuminate patients' experiences of being hospitalised in a hospital with a single-bed room design. INTRODUCTION: Many patients seem to prefer single-bed hospital rooms. However, studies have also shown that patients do see the advantages of multiple-bed rooms. METHOD: Interviews were conducted with 16 inpatients from a surgical ward in a hospital building with a single-bed room design. A hermeneutical-phenomenological approach guided by van Manen's four life-world existentials was used to analyse the interviews. RESULTS: The essential meaning was that patients felt secure because they could create a personal environment without disruptive elements. The room was private, and this implied feelings of homeliness, which allowed patients to focus on themselves and was thought to facilitate the recovery process. The patients preferred staying in their room, and the relationship with the personnel was central. Feelings of loneliness and isolation could occur and could be frightening. Being hospitalised in a single-bed room meant balancing between feeling secure and feeling insecure. The following four themes emerged: A homely environment, The need for company and security, Time as unpredictable and involving waiting and Focus on healing the body. CONCLUSION: Patients experienced that a single-bed room allowed them to focus on their recovery, have visitors without disturbing others and create a feeling of homeliness. However, mobilisation is not a natural part of the recovery process when patients have all they need in their rooms. The patients' need for social interaction and confirmation was not satisfied without effort and planning on the part of staff.

Dynamic Release from Acetalated Dextran Nanoparticles for Precision Therapy of Inflammation.

Polymer-based nanoparticles (NPs) that react to altered physiological characteristics have the potential to enhance the delivery of therapeutics to a specific area. These materials can utilize biochemical triggers, such as low pH, which is prone to happen locally in an inflammatory microenvironment due to increased cellular activity. This reduced pH is neutralized when inflammation subsides. For precise delivery of therapeutics to match this dynamic reaction, drug delivery systems (DDS) need to not only release the drug (ON) but also stop the release (OFF) autonomously. In this study, we use a systematic approach to optimize the composition of acetalated dextran (AcDex) NPs to start (ON) and stop (OFF) releasing model cargo, depending on local pH changes. By mixing ratios of AcDex polymers (mixed NPs), we achieved a highly sensitive material that was able to rapidly release cargo when going from pH 7.4 to pH 6.0. At the same time, the mix also offered a stable composition that enabled a rapid ON/OFF/ON/OFF switching within this narrow pH range in only 90 min. These mixed NPs were also sensitive to biological pH changes, with increased release in the presence of inflammatory cells compared to healthy cells. Such precise and controllable characteristics of a DDS position mixed NPs as a potential treatment platform to inhibit disease flare-ups, reducing both systemic and local side effects to offer a superior treatment option for inflammation compared to conventional systems.

Cartilage destruction in early rheumatoid arthritis patients correlates with CD21-/low double-negative B cells.

BACKGROUND: Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21-/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21-/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. METHODS: Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry. RESULTS: Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21-/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21-/low double-negative (DN, CD27-IgD-) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21-/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). CONCLUSIONS: Cartilage destruction in eRA patients was associated with an expanded proportion of CD21-/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21-/low DN in RA pathogenesis.

Correlation of Professional Antigen-Presenting Tbet+CD11c+ B Cells With Bone Destruction in Untreated Rheumatoid Arthritis.

OBJECTIVE: Subsets of CD21-/low memory B cells (MBCs), including double-negative (DN, CD27-IgD-) and Tbet+CD11c+ cells, are expanded in chronic inflammatory diseases. In rheumatoid arthritis (RA), CD21-/low MBCs correlate with joint destruction. However, whether this is due to the Tbet+CD11c+ subset, its function and pathogenic contribution to RA are unknown. This study aims to investigate the association between CD21-/lowTbet+CD11c+ MBCs and joint destruction as well as other clinical parameters and to elucidate their functional properties in patients with untreated RA (uRA). METHODS: Clinical observations were combined with flow cytometry (n = 36) and single-cell RNA sequencing (scRNA-seq) and V(D)J sequencing (n = 4) of peripheral blood (PB) MBCs from patients with uRA. The transcriptome of circulating Tbet+CD11c+ MBCs was compared with scRNA-seq data of synovial B cells. In vitro coculture of Tbet+CD11c+ B cells with T cells was used to assess costimulatory capacity. RESULTS: CD21-/lowTbet+CD11c+ MBCs in PB correlated with bone destruction but no other clinical parameters analyzed. The Tbet+CD11c+ MBCs have undergone clonal expansion and express somatically mutated V genes. Gene expression analysis of these cells identified a unique signature of more than 150 up-regulated genes associated with antigen presentation functions, including B cell receptor activation and clathrin-mediated antigen internalization; regulation of actin filaments, endosomes, and lysosomes; antigen processing, loading, presentation, and costimulation; a transcriptome mirrored in their synovial tissue counterparts. In vitro, Tbet+CD11c+ B cells induced retinoic acid receptor-related orphan nuclear receptor γT expression in CD4+ T cells, thereby polarizing to Th17 cells, a T cell subset critical for osteoclastogenesis and associated with bone destruction. CONCLUSION: This study suggests that Tbet+CD11c+ MBCs contribute to the pathogenesis of RA by promoting bone destruction through antigen presentation, T cell activation, and Th17 polarization.

Human synovial lubricin expresses sialyl Lewis x determinant and has L-selectin ligand activity.

Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Galß1-3(GlcNAcß1-6)GalNAcα1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation.

Acuity and anxiety from the patient's perspective in the emergency department.

BACKGROUND: Knowledge of a patient's perception of her medical needs and urgency may make it possible for emergency nurses to communicate the triage decision and make the patient understand the assessment and triage category. The aim of this study was to compare the patients' own assessments of their acuity to the triage nurse's assessment, as well as describe patient satisfaction and levels of anxiety. METHODS: A prospective, cross-sectional survey design was used. The sample consisted of 72 patients, 54% of whom were women. Median age was 55.9 years. RESULTS: Agreement between the nurse and patient regarding acuity and triage category was rare. This may have consequences for patient safety, because patients may seek care at an inappropriate level, in both directions. Communication between the nurse and patient during the waiting time in the emergency department is very important, both for patient satisfaction and reduction of anxiety levels. DISCUSSION: Helping the patient understand the severity of his medical condition and providing information about the triage category and its implications for care in the emergency department should be a focus in communication between the triage nurse and patient. It may well be that the patient's anxiety level is reduced and satisfaction increased if the triage code is known and understood by the patient.

Development of outcomes for evaluating emergency care triage: a Delphi approach.

BACKGROUND: Triage is used as standard of care for prioritization and identification of time-critical patients in the emergency department (ED) globally, but it is unclear what outcomes should be used to evaluate triage. Currently used outcomes do not include important time-critical diagnoses and conditions. METHOD: We used 18 Swedish triage experts to collect and assess outcomes for the evaluation of 5-level triage systems. The experts suggested 68 outcomes which were then tested through a modified Delphi approach in three rounds. The outcomes aimed to identify correctly prioritized red patients (in need of a resuscitation team), and orange patients (other time critical conditions). Consensus was pre-defined as 70% dichotomized (positive/negative) concordance. RESULTS: Diagnoses, interventions, mortality, level of care and lab results were included in the outcomes. Positive consensus was reached for 49 outcomes and negative consensus for 7 outcomes, with an 83% response rate. The five most approved outcomes were the interventions Percutaneous coronary intervention, Surgical airway and Massive transfusion together with the diagnoses Tension pneumothorax and Intracerebral hemorrhage that received specific interventions. The outcomes with the clearest disapproval included Admittance to a ward, Treatment with antihistamines and The ordering of a head computed tomography scan. The outcomes were considered valid only if occurring in or from the ED. CONCLUSION: This study proposes a standard of 49 outcomes divided into two sets tied to red and orange priority respectively, to be used when evaluating 5-level priority triage systems; Lund Outcome Set for Evaluation of Triage (LOSET). The proposed outcomes include diagnoses, interventions and laboratory results. Before widespread implementation of LOSET, prospective testing is needed, preferably at multiple sites.

The Future of Online Video Consultations in Primary Care: A Qualitative Study.

The COVID-19 pandemic has significantly increased the use of remote services such as video consultations (VCs). In Sweden, private healthcare providers offering VCs have grown substantially since 2016 and have been controversial. Few studies have focused on physicians' experiences of providing care in this context. Our overall aim was to study physicians' experiences of VCs, here focusing on their suggestions for future improvements. Twenty-two semi-structured interviews were performed with physicians working for an online healthcare provider in Sweden, and analyzed through inductive content analysis. Two themes emerged related to desired future improvements of VCs; blended care and technical innovation.

Radiographic airway abnormalities in untreated early rheumatoid arthritis are associated with peripheral neutrophil activation.

BACKGROUND: The role of the lung for the initiation and progression of rheumatoid arthritis (RA) is still unclear. Up to 10% of RA patients develop interstitial lung disease which remains a clinical challenge. Understanding early disease mechanisms is of great importance. The objective of this study was to determine whether there is an association between peripheral neutrophil phenotypes and presence of pulmonary abnormalities (PA) on chest high-resolution computed tomography (HRCT) in untreated early RA (ueRA). METHODS: Clinical data and blood were collected, and HRCT performed at diagnosis on 30 consecutive anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) positive ueRA patients. HRCTs were evaluated for the presence of RA-associated parenchymal, airway and/or pleural abnormalities. Expression of phenotype markers on neutrophils were determined by flow cytometry. Levels of calprotectin, ACPA and RF were measured using immunoassays. RESULTS: The frequency of having any PA was 60%. Airway abnormalities were present in 50%, parenchymal nodules in 43% and interstitial lung abnormalities (ILA) in 10%. Unsupervised multivariate data analysis showed clustering of any PA with neutrophil activation, parameters of inflammation and RF titres. In univariate analysis, the patients with PA displayed significantly increased CD11b and decreased CD62L expression on neutrophils (1.2-fold, p = 0.014; 0.8-fold, p = 0.012) indicating activation and significantly increased RF IgM titre and CRP (5.7-fold, p = 0.0025; 2.3-fold, p = 0.0035) as compared to no PA. Titres of RF, but not ACPA, correlated with expression of the neutrophil activation marker CD11b. A stratified analysis demonstrated that airway involvement was the PA subtype with the strongest association with neutrophil activation. CONCLUSION: We report a strong association between radiographic airway findings and activation of circulating neutrophils in early RA supporting a role of innate immunity and the lung at disease onset. Our results also indicate different contributions of RF and ACPA in the RA pathogenesis.

Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis.

OBJECTIVE: This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints. METHODS: We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE). RESULTS: Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE. CONCLUSION: A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.

Resistin and insulin/insulin-like growth factor signaling in rheumatoid arthritis.

OBJECTIVE: Human resistin has proinflammatory properties that activate NF-κB-dependent pathways, whereas its murine counterpart is associated with insulin resistance. The aim of this study was to examine potential cross-talk between resistin and insulin/insulin-like growth factor (IGF) signaling in rheumatoid arthritis (RA). METHODS: Levels of IGF-1, IGF binding protein 3, and resistin were measured in the blood and synovial fluid of 60 patients with RA and 39 healthy control subjects. Human RA synovium was implanted subcutaneously into SCID mice, and the mice were treated with resistin-targeting small interfering RNA. Primary synovial fibroblasts from patients with RA, as well as those from patients with osteoarthritis, and the human fibroblast cell line MRC-5 were stimulated with resistin. Changes in the IGF-1 receptor (IGF-1R) signaling pathway were evaluated using histologic analysis, immunohistochemistry, and reverse transcription-polymerase chain reaction. RESULTS: Resistin and IGF-1R showed different expression profiles in RA synovia. Low levels of IGF-1 in RA synovial fluid were associated with systemic inflammation and inversely related to the levels of resistin. Stimulation of synovial fibroblasts with resistin induced phosphorylation of IGF-1R to a degree similar to that with insulin, and also induced phosphorylation of transcription factor Akt. This was followed by gene expression of GLUT1, IRS1, GSK3B, and the Akt inhibitors PTPN and PTEN. Abrogation of resistin expression in vivo reduced the expression of IGF-1R, the phosphorylation of Akt, and the expression of PTPN and PTEN messenger RNA in RA synovium implanted into SCID mice. CONCLUSION: Resistin utilizes the IGF-1R pathway in RA synovia. Abrogation of resistin synthesis in the RA synovium in vivo leads to reductions in the expression of IGF-1R and level of phosphorylation of Akt.

Thresholds for minimum data set quality indicators developed and applied in icelandic nursing homes.

A modified Delphi method was used to determine thresholds for Minimum Data Set quality indicators for Icelandic nursing homes. The thresholds were then applied to quality outcomes in Icelandic nursing homes for the year 2009. The thresholds indicate areas of good or poor care and can be used for planning services. Icelandic nursing homes seem to be doing best in incontinence and nutritional care. However, improvement is needed in care practices for depression, medication, and activity.