The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients

Objective. To assess the inter-rater reliability of the BILAG2004-Pregnancy index for assessment of SLE disease activity in pregnancy. Methods. Pregnant SLE patients were recruited from four centres and assessed separately by two raters/physicians in routine clinical practice. Disease activity was determined using the BILAG2004-Pregnancy index. Reliability was assessed using level of agreement, κ-statistics and analysis of disagreement. Major disagreement was defined as a score difference of A and C/D/E or B and D/E between the two raters, and minor disagreement was a score difference of A and B or B and C between raters. Results. A total of 30 patients (63.3% Caucasian, 13.3% Afro-Caribbean, 16.7% South Asian) were recruited. The majority of patients had low-level disease activity according to the local rater’s assessment, and there was no grade A activity, with grade B activity present in the following systems: mucocutaneous (nine patients), musculoskeletal (two patients), cardiorespiratory (one patient) and renal (one patient). The distribution of disease activity was similar to the external rater’s assessment. Good levels of agreement (>70%) were achieved in all systems. κ-statistics were not appropriate for use in the gastrointestinal, ophthalmic, constitutional and neuropsychiatric systems, as there was minimal variation between patients but good levels of agreement otherwise. There were three major disagreements (0.1 per patient, all differences between B and D/E) and five minor disagreements (0.17 per patient). Conclusion. The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients

The BILAG-2004 systems tally-a novel way of representing the BILAG-2004 index scores longitudinally

Objective. This was an exploratory analysis to develop a new way of representing BILAG-2004 system scores longitudinally that would be clinically meaningful and easier to analyse in comparison with multiple categorical variables. Methods. Data from a multicentre longitudinal study of SLE patients (the BILAG-2004 index and therapy collected at every visit) were used. External responsiveness analysis of the index suggested the possibility of using counts of systems with specified transitions in scores as a basis to analyse the system scores. Exploratory analyses with multinomial logistic regression were used to examine the appropriateness of this new method of analysing BILAG-2004 system scores. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of this approach. Results. There were 1414 observations from 347 patients. A novel method was devised based on counts of systems with defined transitions in score (BILAG-2004 systems tally, BST). It has six components (systems with major deterioration, systems with minor deterioration, systems with persistent significant activity, systems with major improvement, systems with minor improvement and systems with persistent minimal or no activity). This was further simplified (simplified BST, sBST) into three components (systems with active/worsening disease, systems with improving disease and systems with persistent minimal or no activity). Both versions had expected associations with change in therapy. ROC curve analyses demonstrated that both versions had similar good performance characteristics (areas under the curve >0.80) in predicting increase in therapy. Conclusion. The BST and sBST provide alternative approaches to representing BILAG-2004 disease activity longitudinally. Further validation of their use is required

Hepatitis B e antigen status and hepatitis B DNA levels in women of childbearing age with chronic hepatitis B infection screening for clinical trials

BACKGROUND: Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load. AIM: To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials. METHODS: Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18-69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive. RESULTS: Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p108 copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p CONCLUSIONS: Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load

Halogen Oxidation Reactions of (C5Ph5)Cr(CO)3 and Lewis Base Addition To [(C5Ph5)Cr(μ-X)X]2: Electrochemical, Magnetic, and Raman Spectroscopic Characterization of [(C5Ph5)CrX2]2 and (C5Ph5)CrX2(THF) (X = Cl, Br, I). X-ray Crystal Structure of [(C5Ph5)Cr(μ-Cl)Cl]2

The 17-electron complex (C5Ph5)Cr(CO)3 reacts with halogens (C6H5I•Cl2, Br2, and I2) in C6H6 to yield the dimeric oxidation products [(C5Ph5)Cr(m-X)X]2 as thermally stable solids. Reactions with other chlorinating agents similarly yield [(C5Ph5)CrCl2]2. An X-ray crystal structure of [(C5Ph5)Cr(m-Cl)Cl]2 was obtained. The magnetic properties of the Cl2 bridged dimer have been determined and modeled using the usual isotropic hamiltonian which yields J/k = –30 K. Low-temperature (77 K) Raman spectra of solid [(C5Ph5)CrX2]2 (X = Cl, I) allow assignments to be made for the metal-ring and metal halogen stretching modes in the low frequency region (\u3c 600 cm-1). Tetrahydrofuran (THF) cleaves these dimers to yield complexes of the form (C5Ph5)CrX2(THF)

The use of Systemic Lupus Erythematosus Disease Activity Index-2000 to define active disease and minimal clinically meaningful change based on data from a large cohort of systemic lupus erythematosus patients

Objectives. To examine SLEDAI-2000 cut-off scores for definition of active SLE and to determine the sensitivity to change of SLEDAI-2000 for the assessment of SLE disease activity and minimal clinically meaningful changes in score

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

<p>Background: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.</p> <p>The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.</p> <p>Methods/design: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.</p> <p>Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.</p> <p>Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide.</p> <p>Discussion: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.</p&gt

Dust emission model of Lyman-break galaxies

Lyman-break galaxies (LBGs) contain a non-negligible amount of dust. Takeuchi et al. (2003)(T03) constructed a model of the infrared spectral energy distribution (SED) for very young galaxies by taking into account the dust size distribution in the early stage of galaxy evolution, which can be different from that of present-day evolved galaxies. We applied T03 model to LBGs and constructed their expected SED. In order to examine the grain size distribution of dust, we calculated the SEDs based on two distinct type of the distribution models: a single-sized distribution and a power-law distribution with a slope of $dN/da \propto a^{-3.5}$. We found that the single-sized and power-law dust size distributions yield a very similar detectability of LBGs at the submillimetre (submm). We also found that galaxies with a power-law dust distribution have much less flux at mid-infrared (MIR) than the other. Then, we applied the model to a gravitationally lensed LBG \cb (cB58), a unique probe of the dust emission from LBGs. Our model framework well reproduced the hot dust temperature under a natural assumption for this galaxy. We also examined the detectability of LBGs at submm wavelengths in an eight-hour deep survey by ALMA. By integrating over their redshifted SEDs with the observed luminosity functions, we obtained the contribution of LBGs to the cosmic infrared background radiation (CIRB). Although they have non-negligible amount of dust, their contribution was found to be small, especially in the FIR $\sim 200 \mu$m. Thus, we need a strongly obscured population of galaxies which contains a large amount of star formation, at some epoch in the history of the universe.Comment: 12 pages, 11 figures, accepted for publication in A&

Pulmonary Vaccination as a Novel Treatment for Lung Fibrosis

Pulmonary fibrosis is an untreatable, uniformly fatal disease of unclear etiology that is the result of unremitting chronic inflammation. Recent studies have implicated bone marrow derived fibrocytes and M2 macrophages as playing key roles in propagating fibrosis. While the disease process is characterized by the accumulation of lymphocytes in the lung parenchyma and alveolar space, their role remains unclear. In this report we definitively demonstrate the ability of T cells to regulate lung inflammation leading to fibrosis. Specifically we demonstrate the ability of intranasal vaccinia vaccination to inhibit M2 macrophage generation and fibrocyte recruitment and hence the accumulation of collagen and death due to pulmonary failure. Mechanistically, we demonstrate the ability of lung Th1 cells to prevent fibrosis as vaccinia failed to prevent disease in Rag−/− mice or in mice in which the T cells lacked IFN-γ. Furthermore, vaccination 3 months prior to the initiation of fibrosis was able to mitigate the disease. Our findings clearly demonstrate the role of T cells in regulating pulmonary fibrosis as well as suggest that vaccinia-induced immunotherapy in the lung may prove to be a novel treatment approach to this otherwise fatal disease

Stillbirths: recall to action in high-income countries.

Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19,439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.Mater Research Institute – The University of Queensland provided infrastructure and funding for the research team to enable this work to be undertaken. The Canadian Research Chair in Psychosocial Family Health provided funding for revision of the translation of the French web-based survey of care providers.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/S0140-6736(15)01020-