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Abstract Background Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation. Methods This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by ‘static’ (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and ‘dynamic’ (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman’s correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity. Results In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks. Conclusions In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation.

Abstract Background Native American youth, primarily living on reservations, suffer the highest burden of suicide of any racial group in the USA. Implementation and sustainability of culturally grounded, evidence-based interventions are needed to address suicide in Native American populations. For nearly 40 years, Montana has ranked at or near the top nationwide for suicide. Fort Peck Tribal leadership declared a state of emergency in 2010 after six suicides and 20 attempts that occurred over a 5-month period. Methods We used a community-based participatory research approach for adapting the Celebrating Life (CL) program with a specific focus on long-term sustainability, which has demonstrated efficacy in addressing suicide with the White Mountain Apache. The aims were to (1) adapt the CL program intake forms through roundtable discussions, (2) conduct asset and resource mapping to identify community and cultural resources to leverage for the CL program within the Fort Peck context, and (3) develop a sustainability plan for CL in Fort Peck through qualitative approaches informed by the Program Sustainability Assessment Tool. Results Roundtable discussions resulted in adapted intake forms that capture variables relevant to the Fort Peck context. Asset mapping identified 13 community assets and 10 cultural resources to incorporate within the CL implementation process. Focus group discussions yielded four key themes that were incorporated into a plan for sustainability: (1) strategic partnerships, (2) long-term funding, (3) communication planning, and (4) workforce planning and engagement. Conclusions This paper outlines an avenue for using culturally adapted tools to design an implementation system driven by community and cultural assets within tribal communities and for integrating program planning for sustainability early in the implementation process.

Abstract Introduction Hurricanes Irma and Maria made landfall in the US Virgin Islands (USVI) in 2017. To date, there is no published literature available on the experiences of pregnant women in the USVI exposed to these hurricanes. Understanding how hurricanes affect pregnant women is key to developing and executing targeted hurricane preparedness and response policies. The purpose of this study was to explore the experiences of pregnancy and birth among women in the USVI exposed to Hurricanes Irma and Maria. Methods We employed a qualitative descriptive methodology to guide sampling, data collection, and analysis. Semi-structured interviews of 30–60 min in length were conducted with a purposive sample of women (N = 18) in the USVI who were pregnant during or became pregnant within two months after the hurricanes. Interviews were transcribed verbatim and data managed in MAXQDA. Team members developed a codebook, applied codes for content, and reconciled discrepancies. We thematically categorized text according to a socioecological conceptual framework of risk and resilience for maternal-neonatal health following hurricane exposure. Results Women’s experiences were organized into two main categories (risk and resilience). We identified the following themes related to risk at 3 socioecological levels including: (1) individual: changes in food access (We had to go without) and stress (I was supposed to be relaxing); (2) household/community: diminished psychosocial support (Everyone was dealing with their own things) and the presence of physical/environmental hazards (I was really scared); and (3) maternity system: compromised care capacity (The hospital was condemned). The themes related to resilience included: (1) individual: personal coping strategies (Being calm); (2) household/community: mutual psychosocial and tangible support (We shared our resources); and (3) the maternity system: continuity of high-quality care (On top of their game). Conclusions A socioecological approach provides a useful framework to understand how risk and resilience influence the experience of maternal hurricane exposure. As the frequency of the most intense hurricanes is expected to increase, clinicians, governments, and health systems should work collaboratively to implement hurricane preparedness and response plans that address pregnant women’s unique needs and promote optimal maternal-infant health.

Abstract Background Trauma within Native American communities compromises parents’ parenting capacity; thus, increasing childrens’ risk for substance use and suicide over the lifespan. The objective of this manuscript is to describe the Wakȟáŋyeža (Little Holy One) intervention and evaluation protocol, that is designed to break cycles of intergenerational trauma, suicide, and substance use among Fort Peck Assiniboine and Sioux parents and their children. Methods A randomized controlled trial with an embedded single-case experimental design will be used to determine effectiveness of the modular prevention intervention on parent-child outcomes and the added impact of unique cultural lesson-components. Participants include 1) Fort Peck Assiniboine and Sioux parents who have had adverse childhood experiences, and 2) their children (3–5 years). Parent-child dyads are randomized (1:1) to Little Holy One or a control group that consists of 12 lessons taught by Indigenous community health workers. Lessons were developed from elements of 1) the Common Elements Treatment Approach and Family Spirit, both evidence-based interventions, and 2) newly created cultural (intervention) and nutrition (control group only) lessons. Primary outcomes are parent (primary caregiver) trauma symptoms and stress. Secondary outcomes include: Parent depression symptoms, parenting practices, parental control, family routines, substance use, historical loss, communal mastery, tribal identity, historical trauma. Child outcomes include, externalizing and internalizing behavior and school attendance. Primary analysis will follow an intent-to-treat approach, and secondary analysis will include examination of change trajectories to determine impact of cultural lessons and exploration of overall effect moderation by age and gender of child and type of caregiver (e.g., parent, grandparent). Discussion Many Native American parents have endured adverse childhood experiences and traumas that can negatively impact capacity for positive parenting. Study results will provide insights about the potential of a culturally-based intervention to reduce parental distress – an upstream approach to reducing risk for childrens’ later substance misuse and suicidality. Intervention design features, including use of community health workers, cultural grounding, and administration in Head Start settings lend potential for feasibility, acceptability, sustainability, and scalability. Trial registration ClinicalTrials.gov: NCT04201184 . Registered 11 December 2019.

Abstract Background Pain and fatigue are persistent problems in people with rheumatoid arthritis. Central sensitisation (CS) may contribute to pain and fatigue, even when treatment has controlled inflammatory disease. This study aims to validate a self-report 8-item questionnaire, the Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, developed to measure central pain mechanisms in RA, and to predict patient outcomes and response to treatment. A secondary objective is to explore mechanisms linking CS, pain and fatigue in people with RA. Methods/design This is a prospective observational cohort study recruiting 250 adults with active RA in secondary care. The CAP-RA questionnaire, demographic data, medical history, and patient reported outcome measures (PROMs) of traits associated with central sensitization will be collected using validated questionnaires. Quantitative sensory testing modalities of pressure pain detection thresholds, temporal summation and conditioned pain modulation will be indices of central sensitization, and blood markers, swollen joints and ultrasound scans will be indices of inflammation. Primary data collection will be at baseline and 12 weeks. The test-retest reliability of CAP-RA questionnaire will be determined 1 week after the baseline visit. Pain and fatigue data will be collected weekly via text messages for 12 weeks. CAP-RA psychometric properties, and predictive validity for outcomes at 3 months will be evaluated. Discussion This study will validate a simple self-report questionnaire against psychophysical indices of central sensitization and patient reported outcome measures of traits associated with CS in a population of individuals with active RA. The application of this instrument in the clinical environment could provide a mechanism-based stratification tool to facilitate the provision of targeted therapy to individuals with pain and fatigue in RA, alongside treatments that target joint inflammation. Trial registration Clinicaltrials.gov NCT04515589 . Date of registration 17 August 2020.

Abstract Background DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants (1) commencing anti-TNF therapy (n = 10,813), or (2) changing between non-biologic DMARDs (n = 2992), (3) Early Rheumatoid Arthritis Network participants (n = 813), and (4) participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n = 45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA.

Since April 2014, invasive pneumococcal disease incidence has increased substantially across North East England, United Kingdom, reversing the decline that followed the 2006 introduction of pneumococcal conjugate vaccines. Significant increases occurred in 23-valent polysaccharide vaccine serotypes and nonvaccine serotypes. Trends in other regions and long-term effects of multivalent vaccines require further investigation.

Background/Methods: This study determines the co-expression of mammaglobin-A, vascular endothelial growth factor receptor-3 (VEGFR3) and Ki67 by immunohistochemistry (IHC) in tissue samples from 80 patients undergoing breast surgery (cancer or benign disease). The tissue expression was compared with the tumour histopathology and Kaplan Meier 5-year survival analysis was performed. Results: Positive breast tissue expression was observed in 53% samples for mammaglobin, 41% Ki67 and 65% VEGFR3 with a significant positive correlation between Ki67 and VEGFR3 co-expression. Ki67 and VEGFR3 expression correlated with the breast tumour grade and Ki67 expression also correlated with oestrogen receptor (ER) status. At 5 years post-operatively, 6/80 patients had died and 3 patients were alive but had cancer recurrence. High Ki67 expression significantly correlated with poor survival (disease-free and overall). Conclusions: In this study, VEGFR3 and Ki67 expression but not mammaglobin-A correlated with breast tumour pathology. Positive Ki67 expression was also associated with a poor 5-year survival outcome.

ObjectiveTumor necrosis factor alpha-induced protein 3 (TNFAIP3) is an anti-inflammatory protein implicated in multiple autoimmune and rheumatologic conditions. We hypothesized that lower levels of TNFAIP3 contributes to excessive cytokine production in response to inflammatory stimuli in axial spondyloarthritis (AxSpA). A further aim was to determine the immune signaling and genetic variation regulating TNFAIP3 expression in individual subjects.MethodsBlood-derived macrophages from 50 AxSpA subjects and 30 healthy controls were assessed for TNFAIP3 expression. Cell lysates were also analyzed for NF-κB, mitogen-activated protein (MAP) kinase and STAT3 phosphorylation, and supernatants for cytokine production. Coding and regulatory regions in the TNFAIP3 gene and other auto-inflammation-implicated genes were sequenced by next-generation sequencing and variants identified.ResultsMean TNFAIP3 was significantly lower in spondyloarthritis macrophages than controls (p = 0.0085). Spondyloarthritis subject macrophages correspondingly produced more TNF-α in response to lipopolysaccharide (LPS, p = 0.015). Subjects with the highest TNFAIP3 produced significantly less TNF-α in response to LPS (p = 0.0023). Within AxSpA subjects, those on TNF blockers or with shorter duration of disease expressed lower levels of TNFAIP3 (p = 0.0011 and 0.0030, respectively). TNFAIP3 expression correlated positively with phosphorylated IκBα, phosphorylated MAP kinases, and unstimulated phosphorylated STAT3, but negatively with LPS or TNF-α-stimulated fold induction of phosphorylated STAT3. Further, subjects with specific groups of variants within TNFAIP3 displayed differences in TNFAIP3 (p = 0.03–0.004). Nominal pQTL associations with genetic variants outside TNFAIP3 were identified.ConclusionOur results suggest that both immune functional and genetic variations contribute to the regulation of TNFAIP3 levels in individual subjects. Decreased expression of TNFAIP3 in AxSpA macrophages correlated with increased LPS-induced TNF-α, and thus, TNFAIP3 dysregulation may be a contributor to excessive inflammatory responses in spondyloarthritis subjects.

Construction of new BioSafety Level (BSL) 3 and 4 laboratories has raised concerns regarding provision of care to exposed workers because of healthcare worker (HCW) unfamiliarity with precautions required. When the National Institutes of Health began construction of a new BSL-4 laboratory in Hamilton, Montana, USA, in 2005, they contracted with St. Patrick Hospital in Missoula, Montana, for care of those exposed. A care and isolation unit is described. We developed a training program for HCWs that emphasized the optimal use of barrier precautions and used pathogen-specific modules and simulations with mannequins and fluorescent liquids that represented infectious body fluids. The facility and training led to increased willingness among HCWs to care for patients with all types of communicable diseases. This model may be useful for other hospitals, whether they support a BSL-4 facility, are in the proximity of a BSL-3 facility, or are interested in upgrading their facilities to prepare for exotic and novel infectious diseases.

PURPOSE: Acute asthma is a common emergency department (ED) presentation and variation in its management is well recognized. The present study examined the use of an asthma care map (ACM) in one Canadian ED to improve adherence to acute asthma guidelines, emphasizing the use of systemic corticosteroids (SCSs) and inhaled corticosteroids (ICSs).

From July through September 2000, patients in five European countries were infected with a multidrug-resistant strain of Salmonella Typhimurium DT204b. Epidemiologic investigations were facilitated by the transmission of electronic images (Tagged Image Files) of pulsed-field gel electrophoresis profiles. This investigation highlights the importance of standardized protocols for molecular typing in international outbreaks of foodborne disease.

Sweet syndrome (SS) (Acute Febrile Neutrophilic Dermatosis) has been reported in association with autoimmune phenomena including relapsing polychondritis, drug-induced lupus, and the development of antineutrophil cytoplasmic antibodies (ANCAs). However, a combination of these autoimmune features has not been reported. Herein, we report a case of drug-induced bullous SS with ocular and mucosal involvement, glomerulonephritis, and multiple autoimmune features including clinical polychondritis with antitype II collagen antibodies, ANCAs, antinuclear (HEp-2), and antihistone antibodies in a patient on hydralazine and carbamazepine.