Establishing links between organizational climate, employee well-being and historical patient outcomes

This research undertaken in collaboration with Queensland Health analysed the links between dimensions of workplace climate/employee well-being contained in a number of Queensland Health databases, including the Patient Satisfaction Survey, the Clinical Incident database, the compliments and complaints database, the Variable Life Adjusted Display (VLAD) Database and the Better Workplaces Staff Opinion Survey database. Queensland Health sought to identify in what ways workplace climate is related to patient outcomes using existing datasets collected within the Queensland Health Centre for Healthcare Improvement. The process of establishing links involved matching aggregated data for specific facilities (where possible), or failing that, larger facilities (e.g. Hospital), or the Health Service District. Once the datasets had been matched on location or facility, correlations were calculated between the aggregated scores. The results demonstrated links between the data sets. These links showed that a better workplace climate is associated with greater reported numbers of clinical incidents, especially “no harm” clinical incidents. There was also a link between workplace climate and patient compliments/complaints which show that unsolicited compliments received from patients and their families are clearly related to a number of positive aspects of workplace climate (workplace morale, role clarity, and appraisal and recognition) and individual morale. The results linking workplace climate and patient satisfaction showed that there is a strong positive relationship between overall patient satisfaction and role clarity, and a negative relationship between overall patient satisfaction and both workplace distress and excessive work demands. While these results relate to historical data and therefore should not be construed to reflect the current state of operation within Queensland Health, they are still indicative of some very important relationships. This is the first study to demonstrate that more positive clinical management practices, better perceptions of the workplace climate and better employee well-being are a reflection of a better incident reporting and learning culture in a health care organization, ultimately resulting in improved patient outcomes

Temporal extensivity of Tsallis' entropy and the bound on entropy production rate

The Tsallis entropy, which is a generalization of the Boltzmann-Gibbs entropy, plays a central role in nonextensive statistical mechanics of complex systems. A lot of efforts have recently been made on establishing a dynamical foundation for the Tsallis entropy. They are primarily concerned with nonlinear dynamical systems at the edge of chaos. Here, it is shown by generalizing a formulation of thermostatistics based on time averages recently proposed by Carati [A. Carati, Physica A 348, 110 (2005)] that, whenever relevant, the Tsallis entropy indexed by $q$ is temporally extensive: linear growth in time, i.e., finite entropy production rate. Then, the universal bound on the entropy production rate is shown to be $1/|1-q|$ . The property of the associated probabilistic process, i.e., the sojourn time distribution, determining randomness of motion in phase space is also analyzed.Comment: 25 pages, no figure

Differential peripheral B cell phenotype in patients with primary Sjögren’s syndrome (pSS) compared to secondary Sjögren’s syndrome associated with systemic lupus erythematosus (SS/SLE)

Introduction: Peripheral B-cell abnormalities, a feature of both systemic lupus erythematosus (SLE) and primary Sjogren’s syndrome (pSS), are implicated in the pathogenesis of both diseases and correlate with disease activity. This study aims to investigate how the defective B-cell phenotype in pSS patients compares to patients with SS and SLE (SS/SLE), and whether abnormalities in B-cell phenotype could be related to differential B-cell lipid-raft expression and B-cell activating factor (BAFF) receptor function in patients with pSS and SLE and secondary SS (SS/SLE). Methods: Blood samples and clinical and laboratory parameters from 32 patients with pSS and SS/SLE and 13 age/sex matched HC were obtained. We used flow-cytometry to perform B-cell immunophenotyping and analysed lipid-raft expression (marker of B-cell activation). In vitro cultures were also used to assess lipid-raft expression in response to BAFF. Results: Patients with SS/SLE had a significantly decreased Bm1 and Bm5 and increased Bm2 populations compared to HC (p=0.031, p=0.035 and p=0.01, respectively), and increased Bm2 compared to pSS (p=0.027). Bm1-cells were decreased in both pSS and SS/SLE patients compared to HC (p=0.028 and p= 0.031, respectively). Both age and disease duration correlated strongly with Bm2’ cells in SS/SLE patients (r=0.9572, p= 0.0428), and the immunosuppressive treatment correlated negatively with the number of circulating Bm2 and Bm2’ cell in pSS (r = -0.54, p=0.01 and r = -0.56, p=0.008, respectively). B-cells from patients with pSS had a significant increase in lipid-raft expression compared to HC (p=0.01) and patients with SS/SLE (p<0.05). Lipid-raft levels correlated with BAFF-receptor expression in HC and SS/SLE B-cells (p=0.17, r=0.694) but not in pSS patients. Both disease activity score (ESSDAI) and IgG level correlated positively with lipid rafts expression in B cells from patients with pSS (r = 0.79, p=0.004 and r =0.53, p=0.04, respectively). Conclusion: Patients with SS/SLE had more significant B-cell abnormalities compared to HC and pSS, detectable even in a small number of patients. Also the relationship between lipid-raft and BAFF-receptor expression was altered between pSS and SS/SLE patients, and correlated with the disease activity and IgG levels in pSS group, suggesting that therapies targeting BAFF might be particularly successful in the SS/SLE sub-group of patients

Challenges in implementing cardiovascular risk scores for assessment of young people with childhood-onset autoimmune rheumatic conditions

Cardio-vascular risk (CVR) stratification tools have been implemented in clinical practice to guide management decision for primary prevention of cardiovascular disease. Less is known about how we can optimally estimate the CVR in children and adolescents or about the reliability of the risk stratification tools validated in adult populations. Chronic inflammation associated with autoimmune rheumatic disease (ARD) drives an increased risk for accelerated atherosclerosis in patients of all ages. Although the research is less advanced than in adult populations, it is recognized that young people with ARDs with childhood-onset have increased CVR compared to age-matched healthy controls, as supported by studies investigating lipid biomarker profile and markers of endothelial dysfunction. Further research is needed to address the unmet need for adequate CVR identification and management strategies in young people in general, and in those with underlying chronic inflammation in particular. This perspective paper explores various challenges in adequately identifying and managing CVR in younger populations and potential directions for future research

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications

Treatment strategies for Sjögren’s syndrome with childhood onset: a systematic review of the literature

OBJECTIVES: SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to diagnose. Evidence-based guidelines for treatment of juvenile SS are not available due to the rarity of disease and the paucity of research in this patient population. This systematic review aims to summarize and appraise the current literature focused on pharmacological strategies for management of SS with childhood onset. METHODS: PubMed and MEDLINE/Scopus databases up to December 2020 were screened for suitable reports highlighting pharmacological treatment of SS with childhood onset using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 reporting checklist. Animal studies were excluded. RESULTS: A total of 43 studies (34 case reports, 8 mini case series and 1 pilot study) were eligible for analysis. The studies retrieved included girls in 88% (120/137) of cases and had very low confidence levels. HCQ was prescribed for parotid swelling, as well as in association with MTX and NSAIDs in patients with arthritis and arthralgia. Corticosteroids such as long courses of oral prednisone and i.v. methylprednisolone were commonly prescribed for children with severe disease presentations. Rituximab was mainly indicated for mucosa-associated lymphoid tissue lymphoma and renal and nervous system complications. Other conventional DMARDs were prescribed in selected cases with extraglandular manifestations. CONCLUSION: Various therapies are used for the management of juvenile SS and are prescribed based on expert clinician’s opinion. There are currently no good-quality studies that allow clinical recommendations for treatment of SS with childhood onset

Lupus and Sjögren’s syndrome distinct disease endotypes clustered based on activity scores and immune profiles

Background: Sjögren’s syndrome (SS) is a chronic autoimmune disorder affecting approximately 0.1–0.4% of the general population with a female-to-male ratio of 9:1 usually diagnosed in the fourth and fifth decades of life [1]. Clinically, SS is typified by ocular and oral dryness developed as a consequence of the autoimmune process. It may occur either alone, as primary (p)SS, or secondary to other autoimmune disease, often rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis, secondary (s)SS. Objectives: 1) Identify the peripheral B and T cells abnormalities in patients with pSS, secondary SS associated with systemic lupus erythematosus (SLE) and SLE alone in comparison to healthy donors. 2) Correlate immune phenotypes with clinical features and serological parameters. 3) Identify distinct patients’ endotypes relevant for therapeutic strategies. Methods: Blood samples, clinical and laboratory parameters from 28 patients with pSS, 32 SLE, 15 SS/SLE and age/sex-matched HC were obtained. Immunophenotyping and lipid-raft analyses were performed by flow-cytometry. Results: There were distinct CD19+ B cells, and CD4+ and CD8+ T cell subpopulations observed in pSS, SLE and SS/SLE patients compared to healthy donors. SS/SLE have the most striking B cell phenotype abnormalities than patients with pSS or SLE (increased Bm2 cells and decreased early and late Bm5 cells).There were significant positive and negative correlations of immune cells with clinical parameters in pSS, SLE and SS/SLE patients. The fold-change of memory B cells was significantly reduced in all disease groups with comparison to healthy controls. Fold-change of CD8+ T responder cells were significantly reduced in all diseases, and similarly, CD4+ naïve T cells in SLE and SS/SLE. A highly significant increase in CD4+ T regulatory was observed in pSS. Hierarchical clustering of immune cells in patients yielded 5 distinct endotypes, with clustering reflected in patients with similar disease activity scores. Conclusions: This is the first comprehensive immunophenotype analysis performed patients with pSS, SLE and SS/SLE. We identified significant reduction in memory B cells fold-changed in all disease groups, reduction in CD4+ naïve T cells in SLE and SS/SLE and reduction in T responders in all disease CD8+ in comparison to healthy donors. The most significant T cell abnormalities were found in patients with SLE, however a significant correlation between lipid raft expression as marker of cell activation and disease activity score (ESSDAI) was found only in pSS patients. The five distinct disease endotype clustering showed distinct immune profile in patients with overlapping autoimmune conditions which is particularly relevant for stratification of therapy