In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

Volumetric response and pattern of failure of histone altered high grade glioma in adults following management with radiation therapy.

PURPOSE: H3K27M- and H3G34R-mutant gliomas are recently-classified subgroups of high-grade gliomas (HGGs) affecting younger adults. This study aimed to describe patterns of infiltration and failure, and the volumetric response of these tumours to radiotherapy. METHODS: Patients with histone-mutant gliomas aged 16-50 years, managed from 2009 to 2021 were identified and clinical, radiological and histopathological characteristics collected. Tumour volume was assessed on MRI at diagnosis, pre-radiotherapy, month + 1, + 3 and + 5 post-radiation and at relapse. RESULTS: Of 538 IDH1/2 wild-type HGGs, 18(15%) had a histone alteration. Eleven were H3K27M- and 7 H3G34R-mutant respectively. Median age at diagnosis was 20 years (range17-48 years). Median overall survival was 20 months (95%CI 14-29 months). Both H3K27M- and H3G34R-mutant tumours exhibited extensive T2F infiltration involving a median of 4 neuroanatomical subsites at diagnosis. Median volume of disease pre-radiotherapy on T1gd and T2F respectively was 0.5cm3 (IQR:0-1.7cm3) and 11.9 cm3 (IQR:7.5-29.6cm3) for H3K27M and 0.9cm3 (IQR:0-8.4cm3) and 43.8cm3 (IQR:25.2-86.6 cm3) for H3G34R tumours. T2F volume reduction > 50% was observed 3-months post-IMRT in 7(64%) patients with H3K27M and 1(14%) with H3G34R tumours. Fourteen patients had relapsed. Relapse was local-only, distant-only and both in 4(44%), 3(33%) and 2(22%) H3K27M-mutant and 1(20%), 2(40%), and 2(40%) H3G34R-mutant tumours. On last scan before death, leptomeningeal spread was present in 4/8(50%) and 1/5(20%) and subependymal spread in 4/8 (50%) and 0/5 H3K27M- and G34R-mutant cases respectively. CONCLUSION: H3K27M-mutant gliomas are highly responsive to radiotherapy but exhibit high propensity for subsequent leptomeningeal and subependymal spread. H3G34R-mutant tumours exhibit lesser early volumetric response to radiotherapy and propensity for distant in-brain failure.

Risks and treatment related aspects of COVID-19 infection in patients with ANCA-associated vasculitis.

OBJECTIVE: Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) require immunosuppressive therapy for disease control and relapse prevention and may be at risk for severe coronavirus disease 2019 (COVID-19). The study objective was to analyse risk factors and outcomes of COVID-19 in well-characterized AAV patients. METHOD: Data were retrieved from March 2020 to May 2021 from medical records of AAV cohorts in Stockholm and Uppsala, Sweden. COVID-19 was confirmed by positive PCR test or by ELISA. Severe COVID-19 was defined as need for non-invasive ventilation, intensive care unit care, and/or death. Age, gender, ANCA antibody type, ongoing immunosuppressive medication, and estimated glomerular filtration rate were recorded. RESULTS: The cohort comprised 310 AAV patients, of whom 29 (9%) were diagnosed with COVID-19. Four deaths were attributed to COVID-19. Fifteen patients (52%) were on prednisolone in the COVID-19 group and 130 (46%) in the non-COVID group, with significantly higher doses in COVID-19 patients (p < 0.01). Ongoing induction therapy was more prevalent in the COVID-19 group (p < 0.01). Severe COVID-19 was diagnosed in 9/29 (31%). Significant risk factors for severe COVID-19 were impaired kidney function (p = 0.01) and more intense immunosuppressive therapy (p = 0.02), with a trend for age (p = 0.07). Maintenance therapy with rituximab was not associated with severe COVID-19. CONCLUSIONS: Our findings highlight risks and suggest that more attention should be given to optimal AAV treatment in a pandemic situation. They also emphasize the need for continued shielding, mitigation strategies, and effective vaccination of AAV patients.

Comparing post-traumatic stress severity in professional and volunteer Australian firefighters.

BACKGROUND: While extensive research has highlighted increased risk for post-traumatic stress disorder (PTSD) in firefighters, previous research has yielded mixed results regarding the role of work status (professional versus volunteer) in the development of psychopathological symptoms. AIMS: To explore the predictive strength of work status on PTSD or post-traumatic stress symptom severity in a large sample of professional (PFFs) and volunteer (VFFs) Australian firefighters exposed to operational work-related trauma. METHODS: The stratified random sample comprised 1317 PFFs (n = 1148 (87%) males and 13%, n = 169 (13%) females) and 898 VFFs (n = 744 (83%) males and n = 154 (17%) females) who reported having experienced trauma while working or volunteering. Participants completed demographic, health and work-related questions and mental health measures of stress, trauma, PTSD, social support and use of mental health prevention programmes. RESULTS: The results revealed a significant relationship between work status and PTSD, with PFFs reporting higher levels of PTSD symptom severity compared to VFFs. This association persisted after controlling for demographics, health, stress away from work, social support and use of organizational mental health support programmes (debriefing and face-to-face training for mental and physical self-care). CONCLUSIONS: This study suggests the importance of work status in PTSD amongst Australian firefighters exposed to operational trauma. Future research is needed to substantiate our findings and examine why PFFs may be more prone to developing PTSD. Implications for the provision of mental health programmes offered by fire organizations to their members are discussed.

Markers of ovarian reserve are associated with reproductive age acceleration in granulosa cells from IVF patients.

STUDY QUESTION: Is reproductive aging in granulosa cells associated with markers of ovarian reserve? SUMMARY ANSWER: Age acceleration was associated with anti-Mullerian hormone (AMH) levels, antral follicle count (AFC), oocyte yield and maturity, and the number of successfully fertilized embryos. WHAT IS KNOWN ALREADY: The rate of reproductive aging varies among women of the same age. DNA methylation can be used to predict epigenetic age in a variety of tissues. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study of 70 women at the time of oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 70 participants were recruited for this study at an academic medical center and they provided follicular fluid samples at the time of oocyte retrieval. Granulosa cells were isolated and assessed on the MethylationEPIC array. Linear regression was used to evaluate the associations between DNA methylation-based age predictions from granulosa cells and chronological age. Age acceleration was calculated as the residual of regressing DNA methylation-based age on chronological age. Linear regressions were used to determine the associations between age acceleration and markers of ovarian reserve and IVF cycle outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Participants were a mean of 36.7 ± 3.9 years old. In regards to race, 54% were white, 19% were African American and 27% were of another background. Age acceleration was normally distributed and not associated with chronological age. Age acceleration was negatively associated with AMH levels (t = -3.1, P = 0.003) and AFC (t = -4.0, P = 0.0001), such that women with a higher age acceleration had a lower ovarian reserve. Age acceleration was also negatively correlated with the total number of oocytes retrieved (t = -3.9, P = 0.0002), the number of mature oocytes (t = -3.8, P = 0.0003) and the number of fertilized oocytes or two-pronuclear oocytes (t = -2.8, P = 0.008) in the main analysis. LIMITATIONS, REASONS FOR CAUTION: This study used pooled follicular fluid, which does not allow for the investigation of individual follicles. Infertility patients may also be different from the general population, but, as we used granulosa cells, the participants had to be from an IVF population. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated that epigenetic age and age acceleration can be calculated from granulosa cells collected at the time of oocyte retrieval. GrimAge most strongly predicted chronological age, and GrimAge acceleration was associated with baseline and cycle characteristics as well as cycle outcomes, which indicates its potential clinical relevance in evaluating both oocyte quantity and quality. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Institutes of Health (UL1TR002378) and the Building Interdisciplinary Research Careers in Women's Health Program (K12HD085850) to A.K.K. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding source had no role in any aspect of this study. J.B.S. serves as Vice Chair for the American Society for Reproductive Medicine Education Committee, is a Medical Committee Advisor for the Jewish Fertility Foundation and works with Jscreen. J.B.S. has received funding from Georgia Clinical Translational Research Alliance. H.S.H., J.B.S. and A.K.S. have received NIH funding for other projects. A.K.K., S.A.G., S.G., Q.S.K., L.J.M. and W.S. have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

In Silico Finite Element Analysis of the Foot Ankle Complex Biomechanics: A Literature Review.

Computational approaches, especially finite element analysis (FEA), have been rapidly growing in both academia and industry during the last few decades. FEA serves as a powerful and efficient approach for simulating real-life experiments, including industrial product development, machine design, and biomedical research, particularly in biomechanics and biomaterials. Accordingly, FEA has been a "go-to" high biofidelic software tool to simulate and quantify the biomechanics of the foot-ankle complex, as well as to predict the risk of foot and ankle injuries, which are one of the most common musculoskeletal injuries among physically active individuals. This paper provides a review of the in silico FEA of the foot-ankle complex. First, a brief history of computational modeling methods and finite element (FE) simulations for foot-ankle models is introduced. Second, a general approach to build an FE foot and ankle model is presented, including a detailed procedure to accurately construct, calibrate, verify, and validate an FE model in its appropriate simulation environment. Third, current applications, as well as future improvements of the foot and ankle FE models, especially in the biomedical field, are discussed. Finally, a conclusion is made on the efficiency and development of FEA as a computational approach in investigating the biomechanics of the foot-ankle complex. Overall, this review integrates insightful information for biomedical engineers, medical professionals, and researchers to conduct more accurate research on the foot-ankle FE models in the future.

Communication skills teaching for student dietitians using experiential learning and simulated patients.

BACKGROUND: Dietitians require communication competencies for effective dietetic practice. There is little evidence on how student dietitians experience and value communication skills teaching. The present study aimed to measure attitudes of student dietitians with respect to communication skills teaching and how experiential learning using simulated patients impacts confidence in their communication skills. METHODS: Communication skills teaching adopting an experiential skills-based approach including practice with simulated patients, feedback and reflection were developed. A 67-item questionnaire with three sections: (i) views regarding the importance of communication skills to dietetic practice; (ii) attitudes to learning communication skills using a modified Communication Skills Attitude Scale; and (iii) confidence in their own communication skills, was completed by students before and after the course, with responses recorded on a five-point Likert scale and analysed pairwise using McNemar's test. RESULTS: Over three academic years, 112 students (91.8% response rate) completed the evaluation. After training, students rated communication skills as important for patient satisfaction (100%) and relationships with patients (99.1%). Student dietitians had positive attitudes to learning communication skills with positive attitudes scale score before teaching of mean (SD) 53.6 (5.3) and after of 54.0 (5.8) (P = 0.162). Following experiential teaching, the proportion of students feeling 'very or extremely confident' in understanding a patient's perspective increased from 27.7% to 41.1% (P = 0.008) and for reaching agreement with a patient from 4.5% to 17.9% (P = 0.001). CONCLUSIONS: Student dietitians consider communication skills important for dietetic practice. They receive teaching positively and an experiential skills-based approach can improve self-rated confidence.

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in paediatric cutaneous lupus among paediatric dermatologists and rheumatologists.

BACKGROUND: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a reliable outcome measure for cutaneous lupus erythematosus (CLE) in adults used in clinical trials. However, it has not been validated in children, limiting clinical trials for paediatric CLE. OBJECTIVES: This study aimed to validate the CLASI in paediatrics. METHODS: Eleven paediatric patients with CLE, six dermatologists and six rheumatologists participated. The physicians were trained to use the CLASI and Physician's Global Assessment (PGA), and individually rated all patients using both tools. Each physician reassessed two randomly selected patients. Within each physician group, the intraclass correlation coefficient (ICC) was calculated to assess the reliability of each measure. RESULTS: CLASI activity scores demonstrated excellent inter- and intrarater reliability (ICC > 0·90), while the PGA activity scores had good inter-rater reliability (ICC 0·73-0·77) among both specialties. PGA activity scores showed excellent (ICC 0·89) and good intrarater reliability (ICC 0·76) for dermatologists and rheumatologists, respectively. Limitations of this study include the small sample size of patients and potential recall bias during the physician rerating session. CONCLUSIONS: CLASI activity measurement showed excellent inter- and intrarater reliability in paediatric CLE and superiority over the PGA. These results demonstrate that the CLASI is a reliable and valid outcome instrument for paediatric CLE.

Swedish Society of Rheumatology 2018 guidelines for investigation, treatment, and follow-up of giant cell arteritis.

Objective: To develop evidence-based guidelines for the management of giant cell arteritis (GCA) as a complement to guidelines in other areas of rheumatology, issued by the Swedish Society of Rheumatology. Methods: A working group selected key areas for recommendations, reviewed the available evidence, and wrote draft guidelines. These were discussed and revised according to standard procedures within the Swedish Society of Rheumatology, including a one-day meeting open to all members. For key recommendations, the quality of evidence was assessed according to GRADE. The final guidelines were approved by the Society board in March 2018. Results: The guidelines include recommendations on diagnostic procedures, pharmacological treatment, follow-up, and adjuvant treatment. Ultrasonography is complementary to temporal artery biopsy (TAB) in the diagnostic work-up. Other imaging techniques (magnetic resonance imaging and positron emission tomography/computed tomography) are important in evaluating large-vessel involvement. Glucocorticoids (oral, or intravenous in cases with ischaemic complications) remain the first line treatment for GCA. Addition of tocilizumab is recommended for patients with relapsing disease who meet five criteria, representing active disease that has been objectively verified by TAB or imaging. Tocilizumab may also be considered in patients with newly diagnosed GCA who are at major risk of severe glucocorticoid side effects. Based on current evidence, tocilizumab treatment for > 1 year cannot be recommended. Conclusion: These guidelines are based on current evidence and consensus within Swedish rheumatology. Following major developments in diagnostics and treatment of GCA, such guidelines are important for clinical practice, and should be updated on a regular basis.

Super-resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI).

AIMS: The spatial resolution of light microscopy is limited by the wavelength of visible light (the 'diffraction limit', approximately 250 nm). Resolution of sub-cellular structures, smaller than this limit, is possible with super resolution methods such as stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI). We aimed to resolve subcellular structures (axons, myelin sheaths and astrocytic processes) within intact white matter, using STORM and SOFI. METHODS: Standard cryostat-cut sections of subcortical white matter from donated human brain tissue and from adult rat and mouse brain were labelled, using standard immunohistochemical markers (neurofilament-H, myelin-associated glycoprotein, glial fibrillary acidic protein, GFAP). Image sequences were processed for STORM (effective pixel size 8-32 nm) and for SOFI (effective pixel size 80 nm). RESULTS: In human, rat and mouse, subcortical white matter high-quality images for axonal neurofilaments, myelin sheaths and filamentous astrocytic processes were obtained. In quantitative measurements, STORM consistently underestimated width of axons and astrocyte processes (compared with electron microscopy measurements). SOFI provided more accurate width measurements, though with somewhat lower spatial resolution than STORM. CONCLUSIONS: Super resolution imaging of intact cryo-cut human brain tissue is feasible. For quantitation, STORM can under-estimate diameters of thin fluorescent objects. SOFI is more robust. The greatest limitation for super-resolution imaging in brain sections is imposed by sample preparation. We anticipate that improved strategies to reduce autofluorescence and to enhance fluorophore performance will enable rapid expansion of this approach.

Child-onset systemic lupus erythematosus is associated with a higher incidence of myopericardial manifestations compared to adult-onset disease.

OBJECTIVES: There are no population-based estimates of the incidence or risk factors for acute cardiac manifestations in children with systemic lupus erythematosus (SLE) to guide screening and diagnostic imaging practices. We estimated the incidence and prevalence of acute cardiac manifestations of child-onset SLE compared to adult-onset SLE and identified factors associated with cardiac diagnoses. METHODS: We identified children (5-17 years) and adults (18-64 years) with incident SLE (≥3 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 CM) code 710.0, > 30 days apart) using Clinformatics® DataMart (OptumInsight, Eden Prairie, MN) deidentified United States administrative claims (2000-2013). We calculated incidence and prevalence of three outcomes: ≥ 1 diagnosis code for (1) pericarditis and/or myocarditis, (2) endocarditis, or (3) valvular insufficiency. Negative binomial regression was used to identify characteristics associated with cardiac diagnoses in children and determine whether SLE onset in childhood vs adulthood was independently associated with cardiac involvement. RESULTS: There were 297 children and 6927 adults with new-onset SLE. A total of 17.8% of children had ICD-9 CM codes for acute cardiac diagnoses, the incidence of which were highest in the first year after SLE diagnosis (12.2 per 100 person-years). African American race (incidence rate ratio (IRR) 6.6, 95% confidence interval (CI) (2.9, 15.0), p < 0.01) and nephritis (IRR 7.0, 95% CI (2.6, 18.6), p < 0.01) were associated with acute cardiac diagnoses in children. Child-onset disease was independently associated with a 4.4-fold higher rate of pericarditis or myocarditis compared to adult-onset SLE after adjustment for other disease and demographic characteristics (95% CI (2.4, 8.0), p < 0.01). CONCLUSION: This study establishes baseline estimates of the incidence and prevalence of pericarditis and myocarditis in child-onset SLE, which is substantially higher than that of adult-onset SLE. Prospective echocardiographic evaluations are needed to validate incidence measures and characterize the natural history of acute cardiac manifestations in child-onset SLE, as well as identify risk factors for poor cardiac outcomes to inform screening and management.

Use of echocardiography at diagnosis and detection of acute cardiac disease in youth with systemic lupus erythematosus.

Objectives There are no guidelines on the use of echocardiography to detect cardiac manifestations of childhood-onset systemic lupus erythematosus (SLE). We quantify the prevalence of acute cardiac disease in youth with SLE, describe echocardiogram utilization at SLE diagnosis, and compare regional echocardiogram use with incident cardiac diagnoses. Methods Using the Clinformatics® DataMart (OptumInsight, Eden Prairie, MN) de-identified United States administrative database from 2000 to 2013, we identified youth ages 5-24 years with new-onset SLE (≥3 ICD-9 SLE codes 710.0, > 30 days apart) and determined the prevalence of diagnostic codes for pericardial disease, myocarditis, endocarditis, and valvular insufficiency. Multiple logistic regression was used to identify factors associated with echocardiography during the baseline period, up to one year before or six months after SLE diagnosis. We calculated a regional echocardiogram utilization index, which is the ratio of observed use over the mean predicted probability based on all available baseline characteristics. Spearman's rank correlation coefficient was used to evaluate the association between regional echocardiogram utilization indices and percentage of imaged youth diagnosed with their first cardiac manifestation following echocardiography. Results Among 699 youth with new-onset SLE, 18% had ≥ 1 diagnosis code for acute cardiac disease, of which valvular insufficiency and pericarditis were most common. Twenty-five percent of all youth underwent echocardiogram during the baseline period. Regional echocardiogram use was positively correlated with the percentage of imaged youth found to have cardiac disease (ρ = 0.71, p = 0.05). There was up to a five-fold difference in adjusted odds of baseline echocardiography between low- and high-utilizing regions (OR = 0.19, p = 0.007). Conclusion Nearly one-fifth of youth with new-onset SLE have acute cardiac manifestations; however, use of echocardiograms at SLE diagnosis is highly variable. There may be incremental diagnostic value to early use of echocardiography, but prospective studies are needed to determine whether greater use of echocardiograms modifies outcomes.

Wastewater recycling in Antarctica: Performance assessment of an advanced water treatment plant in removing trace organic chemicals.

The Australian Antarctic Division (AAD) operates Australia's Davis Station in the Antarctic. In 2005, Davis Station's wastewater treatment plant failed and since then untreated, macerated effluent has been discharged to the ocean. The objectives of this study were to determine whether an advanced water treatment plant (AWTP) commissioned by the AAD and featuring a multi-barrier process involving ozonation, ceramic microfiltration, biologically activated carbon filtration, reverse osmosis, ultraviolet disinfection and chlorination was capable of producing potable water and a non-toxic brine concentrate that can be discharged with minimal environmental impact. The AWTP was tested using water from a municipal wastewater treatment plant in Tasmania, Australia. We used spot water and passive sampling combined with two multi-residue chromatographic-mass spectrometric methods and a range of recombinant receptor-reporter gene bioassays to screen trace organic chemicals (TrOCs), toxicity and receptor activity in the Feed water, in the environmental discharge (reject water), and product water from the AWTP for six months during 2014-15, and then again for three months in 2016. Across the two surveys we unambiguously detected 109 different TrOCs in the feed water, 39 chemicals in the reject water, and 34 chemicals in the product water. Sample toxicity and receptor activity in the feed water samples was almost totally removed in both testing periods, confirming that the vast majority of the receptor active TrOCs were removed by the treatment process. All the NDMA entering the AWTP in the feed and/or produced in the plant (typically < 50 ng/L), was retained into the reject water with no NDMA observed in the product water. In conclusion, the AWTP was working to design, and releases of TrOCs at the concentrations observed in this study would be unlikely cause adverse effects on populations of aquatic organisms in the receiving environment or users of the potable product water.

Pentraxin 3 in serum and synovial fluid of patients with rheumatoid arthritis with and without autoantibodies.

OBJECTIVES: Pentraxin 3 (PTX3) is a locally produced multifunctional protein involved in inflammation, matrix deposition, and immunity. As patients with seropositive rheumatoid arthritis (RA) have a more severe disease course and higher risk of joint destruction than seronegative patients, the aim of the present study was to examine differences in PTX3 in synovial fluid (SF) (and serum) in seropositive compared to seronegative RA, and other local markers of inflammation and destruction. METHOD: Ninety-seven RA patients with knee effusion were included. Serum and SF levels of PTX3, as well as serum levels of anti-citrullinated protein antibody and rheumatoid factor of immunoglobulin A and M subclasses, and markers of inflammation and potential destruction in SF: white blood cell counts, tumour necrosis factor, interleukin-6, vascular endothelial growth factor, metalloproteinase 3, and cartilage oligomeric matrix protein, were analysed. In addition, a radiographic knee examination was performed. RESULTS: Seropositive patients had significantly higher PTX3 levels in SF than seronegative patients, whereas there was no difference for serum levels. SF-PTX3 levels correlated with disease activity and with local inflammatory markers, especially polymorphonuclear cells, and with autoantibody levels. There was no correlation between PTX3 levels in serum and SF. CONCLUSION: The correlation of disease activity and autoantibody levels with SF-PTX3 levels in antibody-positive patients suggests a role for PTX3 in the inflammatory process specifically in seropositive RA joints, and supports the hypothesis that seropositive and seronegative RA are different disease entities. Polymorphonuclear granulocytes may be an important source of PTX3 in RA SF.

The illness experience of youth with lupus/mixed connective tissue disease: a mixed methods analysis of patient and parent perspectives.

OBJECTIVE: We aimed to develop a model of the illness experience for youth with systemic lupus erythematosus (SLE)/mixed connective tissue disease (MCTD). METHODS: We conducted 32 semi-structured interviews with 16 outpatient youth with SLE/MCTD, age 11 to 22 years, and their parents. We qualitatively defined key features of illness for families and distinguished profiles of youth adapting well vs poorly to SLE/MCTD. We then related these profiles to features of illness, patient-level attributes and outcomes. RESULTS: Experiences with SLE/MCTD grouped into five themes: managing disease, limitations, stigma, illness uncertainty and psychological coping. Youth adapting well experienced minimal challenges in these areas. Youth adapting poorly (4/16) experienced significant challenges in >1 thematic area, and were older with lower socioeconomic status, quality of life and psychosocial functioning, and increased disease-related morbidity. They also described suboptimal treatment adherence, healthcare utilization and transition to adult care. These findings support a dynamic model in which illness adaptation and outcomes are shaped by patient characteristics and five central illness-related challenges. CONCLUSION: Further testing of our model of illness experience may help guide comprehensive and personalized care of youth with SLE/MCTD, with targeted supports for youth at risk for negative adaptation to illness and poor outcomes.

Late-onset neutropenia after rituximab in ANCA-associated vasculitis.

BACKGROUND: Rituximab (RTX) is being used increasingly in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV). Late-onset neutropenia (LON) and risks of infections have been observed following RTX therapy in rheumatological diseases including granulomatosis with polyangiitis (GPA) but data on microscopic polyangiitis (MPA) are lacking. METHOD: We studied the occurrence of LON in 59 AAV (47 GPA/12 MPA) patients treated with RTX. Patient charts were retrospectively reviewed for the occurrence of LON and clinical data were extracted and included in the analysis. RESULTS: Seven of the total 59 patients (11.9%) developed LON after a median time of 86 days (range 56-168 days) since their latest RTX treatment. Of these seven LON patients, 5/47 (10.6%) had a diagnosis of GPA and 2/12 (16.7%) of MPA. Three of the patients developed LON after the first RTX treatment and four had received repeated courses. Five LON patients developed infectious symptoms. Six of the patients were hospitalized. Retreatment with RTX was given in three cases without further LON episodes. CONCLUSIONS: LON is a potentially severe side-effect of RTX occurring in both GPA and MPA and may develop after both single and repeated treatment courses. As infections are commonly seen, the condition requires an increased awareness. No predisposing factors for LON were identified.

Diverticular disease in Scotland: 2000-2010.

AIM: Symptomatic diverticular disease (DD) may be increasing in incidence in western society particularly in younger age groups. This study aimed to describe hospital admission rates and management for DD in Scotland between 2000 and 2010. METHOD: Data were obtained from the Scottish Morbidity Records (SMR01). The study cohort included all patients with a hospital admission and a primary diagnosis of DD of the large intestine (ICD-10 primary code K57). RESULTS: Scottish NHS hospitals reported 90 990 admissions for DD (in 87 314 patients) from 2000 to 2010. The annual number of admissions increased by 55.2% from 6591 in 2000 to 10,228 in 2010, an average annual increase per year of 4.5%. Most of the increase attributable to DD was due to elective day cases (3618 in 2000; 6925 in 2010) a likely consequence of a greater proportion of the population accessing colonoscopy over that time period. There was an 11% increase in inpatient admissions (2973-3303), 60% of these patients being women. Admissions in younger age groups increased proportionally in the later years of the study, and there was an association between DD admissions and greater deprivation. Despite an increase in complicated DD from 22.9% in 2000 to 27.1% in 2010 and a 16.8% increase in emergency inpatient admissions, the rate of surgery fell during the period of study. CONCLUSION: This report supports findings of other population-based studies of western countries indicating that DD is an increasing burden on health service resources, particularly in younger age groups.

Similar worldwide patterns in the sex pheromone signal and response in the oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae).

The response of Grapholita molesta (Busck) males to three-component sex pheromone blends containing a 100% ratio of the major sex pheromone component, (Z)-8-dodecenyl acetate and a 10% ratio of (Z)-8-dodecenol, but with varying ratios of (E)-8-dodecenyl acetate (0.4, 5.4, 10.4, 30.4, and 100.1% E-blends) was tested with populations in eight stone and pome fruit orchards in Europe, Asia, and North and South America. Traps baited with the 5.4% E-blend caught significantly more males than traps with any other blend with all populations. Significantly more males were caught in traps baited with the 10.4% E-blend than in traps with the remaining blends, except with the 0.4% E-blend in Turkey. Significant differences in male moth catches occurred between the other blends with the 0.4>30.4% E-blend, and the 30.4>100.1% E-blend. Male moth catches with the 100.1% E-blend only differed from the hexane control in Chile. No apparent differences were noted to these blends in populations collected from pome or stone fruits. Flight tunnel assays to synthetic blends with a subset of populations were similar to the field results, but the breadth of the most attractive E-blends was wider. Flight tunnel assays also demonstrated a high level of male-female cross-attraction among field-collected populations. Female gland extracts from field-collected populations did not show any significant variation in their three-component blends. The only exceptions in these assays were that long-term laboratory populations were less responsive and attractive, and produced different blend ratios of the two minor components than recently collected field populations.

The relationship between socio-economic status and access to eye health services in the UK: a systematic review.

OBJECTIVES: Lower socio-economic status has been shown to adversely affect access to general health care. This study aims to determine the existence and nature of an association between socio-economic status and access to eye health services in the UK. STUDY DESIGN: Systematic review. METHODS: Search terms were run in four databases and reviewed against a pre-agreed set of inclusion and exclusion criteria by two independent reviewers. Quality of studies was assessed according to calculations of statistical significance, size of effect, primary research question and a quality score against an adapted STROBE checklist. RESULTS: Good quality studies included in the review most commonly concluded that lower socio-economic groups had less access to eye health services than higher socio-economic groups. However there were a comparable number of studies that concluded that there was no association. This discrepancy was largely attributed to different ways of measuring socio-economic status, access, and types of eye health services, and so studies did not compare the same thing. The evidence base was of low quality, limiting the ability of this review to make definitive conclusions. CONCLUSIONS: The review concluded that there is equal and weak evidence of lower socio-economic groups having reduced access to eye health services in the UK, and there being no association. This subject would benefit from further research to improve the quality of the evidence base.

What drives junior doctors to use clinical practice guidelines? A national cross-sectional survey of foundation doctors in England & Wales.

BACKGROUND: Clinical practice guidelines (CPGs) aim to improve patient care, but their use remains variable. We explored attitudes that influence CPG use amongst newly qualified doctors. METHODS: A self-completed, anonymous questionnaire was sent to all Foundation Doctors in England and Wales between December 2012 and May 2013. We included questions designed to measure the 11 domains of the validated Theoretical Domains Framework (TDF). We correlated these responses to questions assessing current and future intention to use CPGs. RESULTS: A total of 13,138 doctors were invited of which 1693 [corrected] (13 %) responded. 1,035 (62.5 %) reported regular CPG use with 575 (34.4 %) applying CPGs 2-3 times per week. A significant minority of 606 (36.6 %) declared an inability to critically appraise evidence. Despite efforts to design a questionnaire that captured the domains of the TDF, the domain scales created had low internal reliability. Using previously published studies and input from an expert statistical group, an alternative model was sought using exploratory factor analysis. Five alternative domains were identified. These were judged to represent: "confidence", "familiarity", "commitment and duty", "time" and "perceived benefits". Using regression analyses, the first three were noted as consistent predictors of both current and future intentions to use CPGs in decreasing strength order. CONCLUSIONS: In this large survey of newly qualified doctors, "confidence", "familiarity" and "commitment and duty" were identified as domains that influence use of CPGs in frontline practice. Additionally, a significant minority were not confident in critically appraising evidence. Our findings suggest a number of approaches that may be taken to improve junior doctors' commitment to CPGs through processes that increase their confidence and familiarity in using CPGs. Despite limitations of a self-reported survey and potential non-response bias, these findings are from a large representative sample and a review of existing implementation strategies may be warranted based on these findings.