Rheumatoid arthritis is getting less frequent—results of a nationwide population-based cohort study

Objectives: The objectives of this study were to examine changes in incidence and prevalence of RA between 1990 and 2014, and to explore if there is any geographic variation in incidence and prevalence of RA in the UK Methods: Design Prospective cohort study Setting Primary care Participants People contributing acceptable data to Clinical Practice Research Datalink (CPRD) between 01/01/1990 and 31/12/2014 were included. Read codes were used to identify RA cases ≥18 years in age. Outcomes Prevalence and incidence rates for each year standardised to the 2014 population. Region specific incidence and prevalence of RA for the year 2014 standardized to the overall population. Results: The incidence and prevalence of RA was 3.81 per 10,000 person-years and 0.67% respectively in 2014. The annual incidence of RA reduced by -1.6%(-0.8% to - 2.5%) between 1990 and 2014, with significant joinpoints at 1994 and 2002. The prevalence of RA increased by 3.7%(3.2% to 4.1%)/year from 1990 to 2005; and reduced by -1.1%(-2.0% to -0.2%)/year between 2005 and 2014. There were significant differences in the occurrence of RA throughout different regions of the UK, with highest incidence in East Midlands, Yorkshire and Humber; and highest prevalence in North East, and Yorkshire and Humber. Conclusion: The incidence of RA is decreasing, with a reduction in prevalence in recent years. There is significant geographic variation in occurrence of RA in UK. Further research is required to identify the reasons underlying this phenomenon so that public-health interventions can be designed to further reduce the incidence of RA

Visual versus automated analysis of [I-123]FP-CIT SPECT scans in parkinsonism

The clinical evaluation of dopamine transporter (DAT) SPECT scans typically relies on visual analysis in combination with an automated semi-quantitative method. The interpretation of the results may be difficult in cases that show disagreement between the two methods on the borderline of abnormality. The frequency and clinical characteristics of such cases are unclear. Automated semi-quantitative analyses and independent visual analyses by two experienced nuclear medicine physicians and four inexperienced raters were performed for 120 patients with clinically uncertain parkinsonism scanned with brain [I-123]FP-CIT SPECT. Agreement was evaluated with kappa statistics. The clinical characteristics of patients who had discrepant findings between the two analysis methods were investigated. The expert raters outperformed nonexperts in terms of agreement between visual and automated analyses (kappa = 0.66, 0.72 vs. 0.23-0.54) and between raters (kappa = 0.81 vs. 0.44-0.63). Twelve patients showed discrepant findings between the visual and automated analyses. These patients were older compared to other patients (p = 0.023), had 17.6 % lower mean striatal tracer binding compared to normal scans (p = 0.003) and 62.7 % higher compared to abnormal scans (p < 0.001). After a minimum of 4.5 years of clinical follow-up, none of these patients developed neurodegenerative parkinsonism. Clinical DAT SPECT scans show discrepancies between visual and automated analyses in 10 % of cases. The patients with discrepant findings are older, show normal to slightly abnormal tracer binding, and importantly, do not develop neurodegenerative parkinsonism syndromes. Visual analyses by experienced raters are reliable, but the diagnostic accuracy in discrepant cases can be improved by an automated method

Increasing the Inflammatory Competence of Macrophages with IL-6 or with Combination of IL-4 and LPS Restrains the Invasiveness of Pancreatic Cancer Cells

Recent studies suggest that pro-inflammatory type M1 macrophages inhibit tumor progression and that anti-inflammatory M2 macrophages enhance it. The aim of this study was to examine the interaction of type M1 and M2 macrophages with pancreatic cancer cells. We studied the migration rate of fluorescein stained pancreatic cancer cells on Matrigel cultured alone or with Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) differentiated macrophages or with Macrophage Colony Stimulating Factor (M-CSF) differentiated macrophages, skewing the phenotype towards pro- and anti-inflammatory direction, respectively. Macrophage differentiation was assessed with flow cytometry and the cytokine secretion in cell cultures with cytokine array. Both GM-CSF and M-CSF differentiated macrophages increased the migration rate of primary pancreatic adenocarcinoma cell line (MiaPaCa-2) and metastatic cell line (HPAF-II). Stimulation with IL6 or IL4+ LPS reversed the macrophages' increasing effect on the migration rate of Mi-aPaCa-2 completely and partly of HPAF-II. Co-culture with MiaPaCa-2 reduced the inflammatory cytokine secretion of GM-CSF differentiated macrophages. Co-culture of macrophages with pancreatic cancer cells seem to change the inflammatory cytokine profile of GM-CSF differentiated macrophages and this might explain why also GM-CSF differentiated macrophages promoted the invasion. Adding IL6 or IL4+ LPS to the cell culture with MiaPaCa-2 and GM-CSF or M-CSF differentiated macrophages increased the secretion of inflammatory cytokines and this could contribute to the reversion of the macrophage induced increase of cancer cell migration rate.Peer reviewe

Risk Factors in Heating, Ventilating, and Air-Conditioning Systemsfor Occupant Symptoms in U.S. Office Buildings: the EPA BASE Study

Nonspecific building-related symptoms among occupants of modern office buildings worldwide are common and may be associated with important reductions in work performance, but their etiology remains uncertain. Characteristics of heating, ventilating, and air-conditioning (HVAC) systems in office buildings that increase risk of indoor contaminants or reduce effectiveness of ventilation may cause adverse exposures and subsequent increase in these symptoms among occupants. We analyzed data collected by the U.S. EPA from a representative sample of 100 large U.S. office buildings--the Building Assessment and Survey Evaluation (BASE) study--using multivariate logistic regression models with generalized estimating equations adjusted for potential personal and building confounders. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between seven building-related symptom outcomes and selected HVAC system characteristics. Among factors of HVAC design or configuration: Outdoor air intakes less than 60 m above the ground were associated with approximately doubled odds of most symptoms assessed. Sealed (non-operable) windows were associated with increases in skin and eye symptoms (ORs= 1.9, 1.3, respectively). Outdoor air intake without an intake fan was associated with an increase in eye symptoms (OR=1.7). Local cooling coils were associated with increased headache (OR=1.5). Among factors of HVAC condition, maintenance, or operation: the presence of humidification systems in good condition was associated with an increase in headache (OR=1.4), whereas the presence of humidification systems in poor condition was associated with increases in fatigue/difficulty concentrating, as well as upper respiratory symptoms (ORs=1.8, 1.5). No regularly scheduled inspections for HVAC components was associated with increased eye symptoms, cough and upper respiratory symptoms (ORs=2.2, 1.6, 1.5). Less frequent cleaning of cooling coils or drip pans was associated with increased headache (OR=1.6). Fair or poor condition of duct liner was associated with increased upper respiratory symptoms (OR=1.4). Most of the many potential risk factors assessed here had not been investigated previously, and associations found with single symptoms may have been by chance, including several associations that were the reverse of expected. Risk factors newly identified in these analyses that deserve attention include outdoor air intakes less than 60 m above the ground, lack of operable windows, poorly maintained humidification systems, and lack of scheduled inspection for HVAC systems. Infrequent cleaning of cooling coils and drain pans were associated with increases in several symptoms in these as well as prior analyses of BASE data. Replication of these findings is needed, using more objective measurements of both exposure and health response. Confirmation of the specific HVAC factors responsible for increased symptoms in buildings, and development of prevention strategies could have major public health and economic benefits worldwide

Inborn Errors of Immunity on the Island of Ireland - a Cross-Jurisdictional UKPID/ESID Registry Report

The epidemiology of inborn errors of immunity (IEI) in the Republic of Ireland was first published in 2005 but has not been updated since. IEI prevalence data from Northern Ireland was last published in 2018. Using data from the United Kingdom Primary Immune Deficiency (UKPID) and European Society for Immunodeficiencies (ESID) registries, we reviewed all registered cases of IEI affecting adult patients ≥ 18 years of age from the two largest immunology specialist centres in Northern Ireland and the Republic of Ireland, respectively and calculated the combined minimum adult prevalence of IEI on the island of Ireland for the first time. We also recorded data pertaining to presenting symptoms of IEI, diagnostic delay, immunoglobulin data, and genetic testing, as well as briefly reporting data pertaining to secondary immunodeficiency in both countries. As of 1 May 2020, we identified a minimum adult IEI prevalence in Ireland of 8.85/100,000 population

Prospective comparison of F-18-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer

Purpose To prospectively compare F-18-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). Methods Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-18-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. Results Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-18-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. Conclusion F-18-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.Peer reviewe

Comparison of five parathyroid scintigraphic protocols

Peer reviewe

Glycoprotein YKL-40 : A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial

Objective YKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission. Methods Ninety-nine patients with early DMARD-naive RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay. Results At the baseline, plasma YKL-40 concentration was 57 +/- 37 ( mean +/- SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-alpha antagonist infliximab was added on the combination treatment. Conclusions High YKL-40 levels were found to be associated with disease activity in early DMARD-naive RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission.Peer reviewe

How has Covid-19 affected mental health nurses and the delivery of mental health nursing care in the UK? Results of a mixed methods study

INTRODUCTION: While evidence has emerged concerning the impact of Covid-19 on the general population and the challenges facing health services, much less is known regarding how the pandemic has directly affected the delivery of mental health nursing care. AIM: This paper aims to explore how Covid-19 has affected the ability of mental health nurses to deliver care in community and inpatient mental health services in the UK. METHOD: We investigated staff reports regarding the impact of the Covid-19 pandemic on mental healthcare and mental health service users in the UK, using a mixed methods online survey. A total of 897 nurses across a range of inpatient and community settings participated. DISCUSSION: Key themes within the data explore: new ways of working; remote working; risks of infection/infection control challenges; and the impact on service users. Targeted guidelines are required to support mental health nurses providing care and support during a pandemic to people in severe mental distress, often in unsuitable environments. IMPLICATIONS FOR PRACTICE: Service developments need to occur alongside tailored guidance and support for staff welfare supported by clear leadership. These findings identify areas requiring attention and investment to prepare for future crises and the consequences of the pandemic