Neuropsychiatric Questionnaires in Systemic Lupus Erythematosus

Patients with systemic lupus erythematosus (SLE) can be affected by a multitude of neurologic and psychiatric symptoms with a wide range of prevalence and severity. Irrespectively from attribution to SLE or other causes, neuropsychiatric (NP) symptoms strongly impact short-term and long-term outcomes,thus NP evaluation during routine clinical practice in SLE should be undertaken regularly. The assessment of NP involvement in SLE patients is challenging and the available diagnostic tools fail to guarantee optimal diagnostic accuracy, sensitivity to changes as well as feasibility in routine clinical care. Standardised questionnaires (both physician-administered and self-reported) can offer valuable help to the treating physician to capture all possible NP syndromes; few SLE-specific NP questionnaire have been developed but validation in large cohort or cross-cultural adaptations are still pending. On the other hand, general instruments have been largely applied to SLE patients. Both kinds of questionnaires can address all possible NP manifestations either globally or, more frequently, focus on specific NP symptoms. These latter have been mainly used in SLE to detect and classify mild and subtle symptoms, more likely to be overlooked during routine clinical assessment such as headache, cognitive impairment and psychiatric manifestations. In conclusion, this literature review highlights a clear case for validation studies in this area and the wider implementation of questionnaires to assess NP involvement is still warranted. The broader use of such instruments could have important consequences; first of all, by standardising symptom assessment, a better definition of the prevalence of NP manifestation across different centres could be achieved. Secondly, prospective studies could allow for the evaluation of clinical significance of mild symptoms and their impact on the patient’s function and quality of life

Accuracy of Protein-Protein Binding Sites in High-Throughput Template-Based Modeling

The accuracy of protein structures, particularly their binding sites, is essential for the success of modeling protein complexes. Computationally inexpensive methodology is required for genome-wide modeling of such structures. For systematic evaluation of potential accuracy in high-throughput modeling of binding sites, a statistical analysis of target-template sequence alignments was performed for a representative set of protein complexes. For most of the complexes, alignments containing all residues of the interface were found. The full interface alignments were obtained even in the case of poor alignments where a relatively small part of the target sequence (as low as 40%) aligned to the template sequence, with a low overall alignment identity (<30%). Although such poor overall alignments might be considered inadequate for modeling of whole proteins, the alignment of the interfaces was strong enough for docking. In the set of homology models built on these alignments, one third of those ranked 1 by a simple sequence identity criteria had RMSD<5 Å, the accuracy suitable for low-resolution template free docking. Such models corresponded to multi-domain target proteins, whereas for single-domain proteins the best models had 5 Å<RMSD<10 Å, the accuracy suitable for less sensitive structure-alignment methods. Overall, ∼50% of complexes with the interfaces modeled by high-throughput techniques had accuracy suitable for meaningful docking experiments. This percentage will grow with the increasing availability of co-crystallized protein-protein complexes

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

A Collaborative Filtering Approach for Protein-Protein Docking Scoring Functions

A protein-protein docking procedure traditionally consists in two successive tasks: a search algorithm generates a large number of candidate conformations mimicking the complex existing in vivo between two proteins, and a scoring function is used to rank them in order to extract a native-like one. We have already shown that using Voronoi constructions and a well chosen set of parameters, an accurate scoring function could be designed and optimized. However to be able to perform large-scale in silico exploration of the interactome, a near-native solution has to be found in the ten best-ranked solutions. This cannot yet be guaranteed by any of the existing scoring functions

Noninvasive Assessment of Coronary Artery Disease in Women: What’s Next?

Significant progress in research has been made in the areas of sex-specific aspects of cardiovascular disease. Despite these advances, coronary artery disease (CAD) is the leading cause of death of women in the Western world. Over the past decade, the focused research on women at risk for ischemic heart disease has helped to clarify our understanding of some of the sex-specific factors, which are important in detecting CAD. In women, the detection and evaluation of physiologically significant CAD is challenging, especially given that traditional tests designed to detect focal areas of coronary artery stenosis are less sensitive and specific in female patients who have a lower prevalence of obstructive coronary disease, greater burden of symptoms, and a high atherosclerotic burden. In this article, we review the available evidence on the role of contemporary cardiovascular imaging techniques in evaluating ischemic heart disease in women

General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries

BACKGROUND: Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice. We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada. METHODOLOGY/PRINCIPAL FINDINGS: We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises. We used the framework to analyse 89 publicly-available jurisdictional plans at similar managerial levels in the five countries. The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. No plan addressed all four domains. Most plans either ignored or were sketchy about non-influenza clinical needs, and about the contribution of general practice to public health beyond surveillance. Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently. CONCLUSIONS: This is the first study to provide a framework to guide general practice planning for pandemic influenza. The framework helped identify critical shortcomings in available plans. Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak. We identify implications for practice and for research

Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies

OBJECTIVE: In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. METHODS: We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966–October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. RESULTS: We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. CONCLUSIONS: We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms

Associations between healthy eating patterns and indicators of metabolic risk in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>Since human diets contain many components that may work synergistically to prevent or promote disease, assessing diet quality may be informative. The purpose of this study was to investigate the association between quality diet, by using Healthy Eating Index (HEI), and metabolic risk indicators in postmenopausal women.</p> <p>Methods</p> <p>This cross-sectional study included a total of 173 Brazilian women, aged 45-75 years, seeking healthcare at a public outpatient center. Food consumption assessed by 24 h-recall food inquiry was used to calculate HEI scores: >80 implied diet good, 80-51 diet "needed improvement", and <51 diet poor. Anthropometric data included: body mass index (BMI = weight/height²), waist-circumference (WC), body fat (%BF) and lean mass (%LM). Data on total cholesterol (TC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), and triglycerides (TG) were also collected. Fisher's Exact test, and logistic regression method (to determine odds ratio, OR) were used in the statistical analysis.</p> <p>Results</p> <p>Overweight and obesity were observed in 75.7% of the participants. Excessive %BF (> 35%) was observed in 56.1%, while %LM was reduced (< 70%) in 78.1%. WC was elevated (≥88 cm) in 72.3%. Based on HEI values, diet quality was good in 3% (5/173), needed improvement in 48.5% (84/173), and was poor in 48.5% (84/173) of the cases. In this group, 75% of women had high intakes of lipids (> 35%), predominantly saturated and monounsaturated fat. On average, plasma TC, LDLC, and TG levels were higher than recommended in 57.2%, 79.2% and 45.1% of the women, respectively, while HDLC was low in 50.8%. There was association between HEI scores and the %BF that it was higher among women with HEI score < 80 (p = 0.021). There were not observed significant risk associations between HEI and lipid profile.</p> <p>Conclusion</p> <p>Among the Brazilian postmenopausal women attending a public outpatient clinic, diet was considered to need improvement or to be of poor quality, attributed to high saturated fat ingestion, which probably caused a negative impact on metabolic risk indicators, namely body composition.</p

2021 DORIS definition of remission in SLE: final recommendations from an international task force

OBJECTIVE: To achieve consensus on a definition of remission in SLE (DORIS). BACKGROUND: Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. METHODS: Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. RESULTS: Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. CONCLUSION: The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies