Early symptoms of systemic lupus erythematosus (SLE) recalled by 339 SLE patients.

Objective The European League Against Rheumatism and the American College of Rheumatology jointly embarked on a new classification criteria for systemic lupus erythematosus (SLE) project. Its first phase involved generation of a broad set of items potentially useful for classification of SLE. This study was undertaken to add the patient perspective to an expert Delphi approach and an early patient cohort study. Methods A national cross-sectional study was conducted. A self-report questionnaire was published in the "Schmetterling" (Butterfly), the quarterly journal of the German SLE patient association. Individuals with SLE were asked to anonymously complete the questionnaire, which asked for demographic details, organ manifestations, autoantibodies and symptoms. Results A total of 339 completed questionnaires out of 2498 were returned, a response rate of 13.6%; 83.2% reported they were ANA positive and 81.7% reported joint, 66.1% skin and 33.0% renal involvement. For the time before and in the first year after their SLE diagnosis, the majority reported fatigue (89.4%), joint pain (86.7%), photosensitivity (79.4%) and myalgia (76.1%). Of interest, more than half of the patients reported fever as an early symptom (53.7%). Conclusion For a Caucasian European SLE patient population, the overall characteristics suggest meaningful representation. While many symptoms were reported as expected, the high percentage of patients reporting fever and the significant number of patients with unexpected gastrointestinal complaints are of particular interest. These data add to the information on early SLE symptoms informing the development process of new SLE classification criteria.

There is a need for new systemic sclerosis subset criteria. A content analytic approach.

OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

Whole-exome sequencing for mutation detection in pediatric disorders of insulin secretion: Maturity onset diabetes of the young and congenital hyperinsulinism.

BACKGROUND: To assess the utility of whole-exome sequencing (WES) for mutation detection in maturity-onset diabetes of the young (MODY) and congenital hyperinsulinism (CHI). MODY and CHI are the two commonest monogenic disorders of glucose-regulated insulin secretion in childhood, with 13 causative genes known for MODY and 10 causative genes identified for CHI. The large number of potential genes makes comprehensive screening using traditional methods expensive and time-consuming. METHODS: Ten subjects with MODY and five with CHI with known mutations underwent WES using two different exome capture kits (Nimblegen SeqCap EZ Human v3.0 Exome Enrichment Kit, Nextera Rapid Capture Exome Kit). Analysis was blinded to previously identified mutations, and included assessment for large deletions. The target capture of five exome capture technologies was also analyzed using sequencing data from >2800 unrelated samples. RESULTS: Four of five MODY mutations were identified using Nimblegen (including a large deletion in HNF1B). Although targeted, one mutation (in INS) had insufficient coverage for detection. Eleven of eleven mutations (six MODY, five CHI) were identified using Nextera Rapid (including the previously missed mutation). On reconciliation, all mutations concorded with previous data and no additional variants in MODY genes were detected. There were marked differences in the performance of the capture technologies. CONCLUSIONS: WES can be useful for screening for MODY/CHI mutations, detecting both point mutations and large deletions. However, capture technologies require careful selection.

The impact of simulation education on self-efficacy towards teaching for nurse educators.

AIM: The objective of this study was to assess the impact of a simulation workshop on self-efficacy towards teaching for nurse educators in India. Additionally, we sought to revise and validate a tool to measure self-efficacy in teaching for use with a global audience. BACKGROUND: Simulation is an evidence-based teaching and learning method and is increasingly used in nursing education globally. INTRODUCTION: As new technology and teaching methods such as simulation continue to evolve, it is important for new as well as experienced nurse educators globally to have confidence in their teaching skills and abilities. METHODS: The study included (1) instrument revision, and measures of reliability and validation, (2) an 8-h faculty development workshop intervention on simulation, (3) pre- and post-survey of self-efficacy among nurse educators, and (4) investigation of relationship between faculty socio-demographics and degree of self-efficacy. RESULTS: The modified tool showed internal consistency (r = 0.98) and was validated by international faculty experts. There were significant improvements in total self-efficacy (P < 0.001) and subscale scores among nurse educators after the simulation workshop intervention when compared to pre-survey results. No significant relationships were found between socio-demographic variables and degree of self-efficacy. DISCUSSION: Strong self-efficacy in teaching among nurse educators is crucial for effective learning to occur. CONCLUSIONS AND IMPLICATIONS FOR NURSING: Results indicated the simulation workshop was effective in significantly improving self-efficacy towards teaching for nurse educators using an internationally validated tool. IMPLICATIONS FOR NURSING POLICY: The Minister of Health in India recently called for improvements in nursing education. Introducing nursing education on simulation as a teaching method in India and globally to improve self-efficacy among teachers is an example of a strategy towards meeting this call.

Impact of Left Ventricular Diastolic Dysfunction on Lung Transplantation Outcome in Patients With Pulmonary Arterial Hypertension.

Diastolic dysfunction may influence perioperative outcome, early graft function, and long-term survival. We compared the outcomes of double lung transplantation (DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative left ventricular (LV) diastolic dysfunction with the outcomes of patients without diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent transplantation between January 1995 and December 2013), 44 met our inclusion and exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction pretransplantation had a higher body mass index (29 [IQR 21.5-32.6] vs 22.4 [IQR 19.9-25.3] kg/m2 ) and mean pulmonary arterial pressure (54.6 ± 10 mmHg vs 47 ± 11.3 mmHg) and right atrial pressure (16.5 ± 5.2 mmHg vs 10.6 ± 5.2 mmHg). The patients received extracorporeal life support more frequently (33% vs 7% [p = 0.02]), had worse APACHE II scores (21.7 ± 7.4 vs 15.3 ± 5.3 [p = 0.02]), and a trend toward worse ventilator-free days (2.5 [IQR 6.5-32.5] vs 17 [IQR 3-23] [p = 0.08]). There was no effect on development of primary graft dysfunction or intensive care unit/hospital survival. One-year survival was worse (hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3-22, p = 0.02). Diastolic dysfunction was the only variable that correlated with overall survival (HR 5.4, 95% CI 1.3-22, p = 0.02). Diastolic dysfunction leads to early postoperative morbidity and worse survival in patients with PAH after DLTx.

Toward new criteria for systemic lupus erythematosus-a standpoint.

While clearly different in their aims and means, classification and diagnosis both try to accurately label the disease patients are suffering from. For systemic lupus erythematosus (SLE), this is complicated by the multi-organ nature of the disease and by our incomplete understanding of its pathophysiology. Hallmarks of SLE are the presence of antinuclear antibodies (ANA), and multiple immune-mediated organ symptoms that are largely independent. In an attempt to overcome limitations of the current sets of SLE classification criteria, a new four-phase approach is being developed, which is jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). This review attempts to delineate the performance of the current sets of criteria, the reasons for the decision for classification, and not diagnostic, criteria, and to provide a background of the current approach taken.

Bone disease in systemic sclerosis: outcomes and associations.

OBJECTIVES: The relationship between systemic sclerosis (SSc) and low bone mineral density (BMD) is poorly understood. The aim of this study is to improve our understanding of low bone density in SSc and its potential consequences. METHODS: Fifty consecutive unselected SSc patients were approached. Demographics, disease manifestations, BMD (lumbar spine and femoral neck) were collected at baseline and occurrence of fracture and death were collected over 2 years. The 10-year risk of osteoporotic fracture was estimated using the fracture risk assessment tool (FRAX) v2.0 with the Canadian population reference. Fisher's Exact and Student's t-tests were used to evaluate differences between patients with and without low BMD. Logistic regression was used for multivariate analysis. RESULTS: Forty-five patients had complete BMD data. Twenty-eight patients (62%) had low BMD, of those 10 (36%) had osteoporosis. There was no difference in age, sex, or disease duration between both groups. Low BMD was associated with non-Caucasian race (57% vs. 18%, p=0.01), postmenopausal status (83% vs. 47%, p<0.01), low body mass index (24.5 vs. 26.2, p=0.05). The mean 10-year risk of developing a major osteoporotic fracture and a femoral neck fracture was higher in the low BMD group (10.2% vs. 4.8%, p=0.12) and (4.1% vs. 0.5%, p = 0.16) respectively. Fourteen percent (4/28) of SSc patients with low BMD had a fracture, compared to 6% (1/17) SSc patients without low BMD. Fracture-related mortality did not occur in any patients. CONCLUSIONS: Low BMD and fracture are frequently seen in SSc patients. A number of clinically relevant factors are associated with low BMD. Further research is needed to evaluate these factors and the role of bone-specific treatments in SSc.

Reliability of the American Society of Anesthesiologists physical status scale in clinical practice.

BACKGROUND: Previous studies, which relied on hypothetical cases and chart reviews, have questioned the inter-rater reliability of the ASA physical status (ASA-PS) scale. We therefore conducted a retrospective cohort study to evaluate its inter-rater reliability and validity in clinical practice. METHODS: The cohort included all adult patients (≥18 yr) who underwent elective non-cardiac surgery at a quaternary-care teaching institution in Toronto, Ontario, Canada, from March 2010 to December 2011. We assessed inter-rater reliability by comparing ASA-PS scores assigned at the preoperative assessment clinic vs the operating theatre. We also assessed the validity of the ASA-PS scale by measuring its association with patients' preoperative characteristics and postoperative outcomes. RESULTS: The cohort included 10 864 patients, of whom 5.5% were classified as ASA I, 42.0% as ASA II, 46.7% as ASA III, and 5.8% as ASA IV. The ASA-PS score had moderate inter-rater reliability (κ 0.61), with 67.0% of patients (n=7279) being assigned to the same ASA-PS class in the clinic and operating theatre, and 98.6% (n=10 712) of paired assessments being within one class of each other. The ASA-PS scale was correlated with patients' age (Spearman's ρ, 0.23), Charlson comorbidity index (ρ=0.24), revised cardiac risk index (ρ=0.40), and hospital length of stay (ρ=0.16). It had moderate ability to predict in-hospital mortality (receiver-operating characteristic curve area 0.69) and cardiac complications (receiver-operating characteristic curve area 0.70). CONCLUSIONS: Consistent with its inherent subjectivity, the ASA-PS scale has moderate inter-rater reliability in clinical practice. It also demonstrates validity as a marker of patients' preoperative health status.

Hypoglycaemia, fear of hypoglycaemia and quality of life in children with Type 1 diabetes and their parents.

AIM: To evaluate the association between fear of hypoglycaemia, episodes of hypoglycaemia and quality of life in children with Type 1 diabetes and their parents. METHODS: This was a cross-sectional, population-based study of 325 children with Type 1 diabetes and their parents. The children were aged 2-18 years. A total of 325 parents of the patients aged 2-18 years and 196 of the patients themselves (aged 8-18 years) completed questionnaires including the PedsQL Diabetes Module, the Hypoglycaemia Fear Survey and Clarke's hypoglycaemia awareness questionnaire. Data were compared with HbA1c results and the history of severe hypoglycaemia episodes. RESULTS: Parents with the highest levels of fear of hypoglycaemia reported that their children had a reduced quality of life (P < 0.001). Similarly children with the greatest fear also reported a reduced quality of life (P < 0.001); however a history of severe hypoglycaemia was not associated with the child's quality of life as perceived by the child or parent. Episodes of severe hypoglycaemia were associated with an increased fear of hypoglycaemia for the parents (P = 0.004) but not the children. Children in the highest fear quartile also had a higher HbA(1c) concentration compared with those in the lowest fear quartile [increase in HbA(1c) 7 mmol/mol (0.6%), P < 0.01]. CONCLUSIONS: Fear of hypoglycaemia and not episodes of hypoglycaemia per se is associated with increased psychological burden for children with Type 1 diabetes. Interventions to reduce fear of hypoglycaemia in these families may improve their quality of life.

CCR3 induced-p42/44 MAPK activation protects against staurosporine induced-DNA fragmentation but not apoptosis in airway smooth muscle cells.

BACKGROUND: Chemokine receptors (CCRs) are expressed on airway smooth muscle (ASM) cells. As their ligands are present in the airways in asthma, we hypothesized that ASM CCR activation could promote the increase in ASM mass seen in patients with chronic asthma. OBJECTIVE: To determine which CCRs are expressed by ASM cells and their potential functional relevance to the chronic airway changes seen in asthma. METHODS: CCR expression in primary ASM cell cultures and airway biopsies from patients with and without asthma was examined by RT-PCR, fluorescence-activated cell sorting and immunohistochemistry. ASM p42/44 MAPK activity, proliferation, migration and apoptosis were examined by western blotting, thymidine incorporation, transwell assay and TUNEL assay respectively. RESULTS: CCR3 was the most frequently expressed CCR protein and was present on 79 ± 14% of cells. CX3CR1 and CXCR6 were present on 6% and 11% of cells respectively. CCR3 ligands CCL11 and CCL24 caused rapid activation of p42/44 MAPK but not Akt. CCR3 activation did not affect ASM proliferation, migration or VEGF secretion. DNA fragmentation detected by TUNEL staining could be induced by staurosporine and Fas activation although only Fas activation resulted in caspase 3 cleavage. CCL11 and CCL24 protected ASM cells against DNA fragmentation dependent upon p42/44 MAPK activity only via caspase 3 independent pathways. CCR3 was expressed in the smooth muscle and epithelium in the airways of patients with and without asthma. Smooth muscle cell DNA fragmentation in the airways of patients with stable asthma and controls was very uncommon. CONCLUSIONS AND CLINICAL RELEVANCE: CCR3 is strongly expressed by ASM cells in vitro and in vivo. Protection against cell death by CCR3 activation is dependent on p42/44 MAPK but does not affect caspase 3 mediated apoptosis.

Prognostic factors for survival in systemic lupus erythematosus associated pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension (PH) is a rare but severe manifestation of systemic lupus erythematosus (SLE) that can ultimately result in death. The identification of factors that prognosticate survival in SLE-PH is necessary for appropriate monitoring, timing of therapeutics and lung transplantation. The primary objective of this study was to identify prognostic factors for survival in SLE-PH through review of the literature. The methodological quality of the prognostic studies was also evaluated. METHODS: A systematic review of the literature was performed to identify studies evaluating prognostic factors for survival in SLE-PH. Medline, EMBASE, CINAHL, and Cochrane Central Registry of Controlled Trials (inception - week 2 2010) were searched. A standardized abstraction form was used by two independent reviewers to extract prognostic factors. Methodological quality was evaluated using a validated quality index. RESULTS: Twenty-three observational studies from 375 citations were evaluated. Elevated mean pulmonary artery pressure, Raynaud's phenomenon, thrombocytopenia, plexiform lesion, infection, thrombosis, pregnancy, pulmonary vasculitis and anticardiolipin antibodies were associated with decreased survival. Lupus disease activity, nephritis and central nervous system disease were not associated with survival. The sample sizes were small and methodological quality of the studies was variable. CONCLUSION: This study summarizes factors that may be associated with decreased survival in SLE-PH. The small sample sizes and variable methodological quality preclude definitive conclusions. This study provides the groundwork for further research using large cohorts.

The structure, thermal properties and phase transformations of the cubic polymorph of magnesium tetrahydroborate.

The structure of the cubic polymorph of magnesium tetrahydroborate (γ-Mg(BH(4))(2)) has been determined in space group Ia3d from a structural database of the isoelectronic compound SiO(2); this has been corroborated by DFT calculations. The structure is found to concur with that recently determined by Filinchuk et al. (Y. Filinchuk, B. Richter, T. R. Jensen, V. Dmitriev, D. Chernyshov and H. Hagemann, Angew. Chem. Int. Ed., 2011, DOI: 10.1002/anie.201100675). The phase transformations and subsequent decomposition of γ-Mg(BH(4))(2) on heating have been ascertained from variable-temperature synchrotron X-ray diffraction data combined with thermogravimetric and mass spectrometry measurements. At ~160 °C, conversion to a disordered variant of the ß-Mg(BH(4))(2) phase (denoted as ß') is observed along with a further unidentified polymorph. There is evidence of amorphous phases during decomposition but there is no direct crystallographic indication of the existence of Mg(B(12)H(12)) or other intermediate Mg-B-H compounds. MgH(2) and finally Mg are observed in the X-ray diffraction data after decomposition.

Discoidin domain receptor 1 regulates bronchial epithelial repair and matrix metalloproteinase production.

Discoidin domain receptor (DDR)1 is an extracellular matrix (ECM)-sensing receptor tyrosine kinase, which is activated by collagen and expressed in bronchial epithelium. DDR1 is responsible for maintaining the normal structure of skin and kidney epithelia and we hypothesised that DDR1 plays a regulatory role in bronchial epithelial integrity by transducing signals from the airway ECM. Effects of DDR1 depletion were studied using RNA interference in primary human bronchial epithelial cells (HBECs) and BEAS-2B cells. The effects of overexpression of DDR1a and DDR1b in BEAS-2B cells were studied using a plasmid vector. We measured the effects on epithelial repair using a scratch wounding model, and levels of matrix metalloproteinases (MMPs) by gelatin zymography (MMP-2 and -9) and ELISA (MMP-7). We showed that knockdown of DDR1 slowed epithelial repair by 50%, which was associated with a reduction in levels of MMP-7, whilst DDR1 overexpression enhanced epithelial repair. DDR1 knockdown reduced proliferation of HBECs, but had no significant effect on adhesion to collagen I or other matrix substrates. These data suggest that ECM signalling via DDR1 regulates aspects of bronchial epithelial repair, integrity and MMP expression in the airways.

Studies to further investigate the inhibition of human liver microsomal CYP2C8 by the acyl-ß-glucuronide of gemfibrozil.

In previous studies, gemfibrozil acyl-ß-glucuronide, but not gemfibrozil, was found to be a mechanism-based inhibitor of cytochrome P450 2C8. To better understand whether this inhibition is specific for gemfibrozil acyl-ß-glucuronide or whether other glucuronide conjugates are potential substrates for inhibition of this enzyme, we evaluated several pharmaceutical compounds (as their acyl glucuronides) as direct-acting and metabolism-dependent inhibitors of CYP2C8 in human liver microsomes. Of 11 compounds that were evaluated as their acyl glucuronide conjugates, only gemfibrozil acyl-ß-glucuronide exhibited mechanism-based inhibition, indicating that CYP2C8 mechanism-based inhibition is very specific to certain glucuronide conjugates. Structural analogs of gemfibrozil were synthesized, and their glucuronide conjugates were prepared to further examine the mechanism of inhibition. When the aromatic methyl groups on the gemfibrozil moiety were substituted with trifluoromethyls, the resulting glucuronide conjugate was a weaker inhibitor of CYP2C8 and mechanism-based inhibition was abolished. However, the glucuronide conjugates of monomethyl gemfibrozil analogs were mechanism-based inhibitors of CYP2C8, although not as potent as gemfibrozil acyl-ß-glucuronide itself. The ortho-monomethyl analog was a more potent inhibitor than the meta-monomethyl analog, indicating that CYP2C8 favors the ortho position for oxidation and potential inhibition. Molecular modeling of gemfibrozil acyl-ß-glucuronide in the CYP2C8 active site is consistent with the ortho-methyl position being the favored site of covalent attachment to the heme. Moreover, hydrogen bonding to four residues (Ser100, Ser103, Gln214, and Asn217) is implicated.

Optical evidence of a quantum well channel in low temperature molecular beam epitaxy grown Ga(AsBi)/GaAs nanostructure.

A Ga(AsBi) quantum well (QW) with Bi content reaching 6% and well width of 11 nm embedded in GaAs is grown by molecular beam epitaxy at low temperature and studied by means of high-resolution x-ray diffraction, photoluminescence (PL), and time-resolved PL. It is shown that for this growth regime, the QW is coherently strained to the substrate with a low dislocation density. The low temperature PL demonstrates a comparatively narrow excitonic linewidth of ∼ 40 meV. For high excitation density distinct QW excited states evolve in the emission spectra. The origins of peculiar PL dependences on temperature and excitation density are interpreted in terms of intra-well optical transitions.

Cancer, employment, and American Indians: A participatory action research pilot study.

American Indian cancer survivors are an underserved and understudied group. In this pilot study we attempted to address, through participatory action research, missing information about those factors that serve to either facilitate employment or hinder it for adult cancer survivors. One task of the study was to develop and/or modify instrumentation that could be used in a subsequent, in-depth census study. The pilot sample consisted of 10 cancer survivors, all members of a Northern Minnesota American Indian tribe, and 10 family members. All survivors reported having health problems such as fatigue since their cancer treatments. Rehabilitation counselors can assist survivors and their family members by advising them in regard to employment discrimination and accommodations such as flexible work schedules.

Pulmonary Lymphangioleiomyomatosis originates in the pleural mesothelial cell population.

Lymphangioleiomyomatosis (LAM) is a cystic lung disease mainly affecting women, in which degradation of the lung parenchyma is associated with a cell of unknown provenance, known as a LAM cell. LAM cells carry TSC2 mutations and can be identified in the lung parenchyma by their expression of both smooth muscle actin and antigens characteristic of melanocytes and melanocytic tumors. The nature of the cell-of-origin of LAM is controversial, and despite continued research effort remains elusive. Further, it has not been possible to culture pulmonary LAM cells in vitro, and current research relies on cells and animal models which may not recapitulate all features of the disease. We noted aberrant expression of melanoma antigens in pleural mesothelial cells in lung tissue from LAM patients, indicating that these cells could be the precursors of parenchymal LAM cells. We hypothesise that loss of tuberin function following TSC2 mutation in the mesothelial cell lineage gives rise to the cell-of-origin of pulmonary LAM (P-LAM), and of other associated conditions commonly noted in LAM patients. The unique properties of mesothelial cells provide a straightforward explanation of the diverse presentation of LAM.

Contaminant concentrations in Asian carps, invasive species in the Mississippi and Illinois Rivers.

Populations of invasive fishes quickly reach extremely high biomass. Before control methods can be applied, however, an understanding of the contaminant loads of these invaders carry is needed. We investigated differences in concentrations of selected elements in two invasive carp species as a function of sampling site, fish species, length and trophic differences using stable isotopes (delta (15)N, delta (13)C). Fish were collected from three different sites, the Illinois River near Havana, Illinois, and two sites in the Mississippi River, upstream and downstream of the Illinois River confluence. Five bighead carp (Hypophthalmichthys nobilis) and five silver carp (Hypophthalmichthys molitrix) from each site were collected for muscle tissue analyses. Freshwater mussels (Amblema plicata) previously collected in the same areas were used as an isotopic baseline to standardize fish results among sites. Total fish length, trophic position, and corrected (13)C, were significantly related to concentrations of metals in muscle. Fish length explained the most variation in metal concentrations, with most of that variation related to mercury levels. This result was not unexpected because larger fish are older, giving them a higher probability of exposure and accumulation of contaminants. There was a significant difference in stable isotope profiles between the two species. Bighead carp occupied a higher trophic position and had higher levels of corrected (13)C than silver carp. Additionally bighead carp had significantly lower concentrations of arsenic and selenium than silver carp. Stable isotope ratios of nitrogen in Asian carp were at levels that are more commonly associated with higher-level predators, or from organisms in areas containing high loads of wastewater effluent.

The UK guidelines for management and surveillance of Tuberous Sclerosis Complex.

BACKGROUND: The severity of Tuberous Sclerosis Complex (TSC) can vary among affected individuals. Complications of TSC can be life threatening, with significant impact on patients' quality of life. Management may vary dependent on treating physician, local and national policies, and funding. There are no current UK guidelines. We conducted a Delphi consensus process to reach agreed guidance for the management of patients with TSC in the UK. METHODS: We performed a literature search and reviewed the 2012/13 international guideline for TSC management. Based on these, a Delphi questionnaire was formed. We invited 86 clinicians and medical researchers to complete an online survey in two rounds. All the people surveyed were based in the UK. Clinicians were identified through the regional TSC clinics, and researchers were identified through publications. In round one, 55 questions were asked. In round two, 18 questions were asked in order to obtain consensus on the outstanding points that had been contentious in round one. The data was analysed by a core committee and subcommittees, which consisted of UK experts in different aspects of TSC. The Tuberous Sclerosis Association was consulted. RESULTS: About 51 TSC experts took part in this survey. Two rounds were required to achieve consensus. The responders were neurologists, nephrologists, psychiatrist, psychologists, oncologists, general paediatricians, dermatologist, urologists, radiologists, clinical geneticists, neurosurgeons, respiratory and neurodisability clinicians. CONCLUSIONS: These new UK guidelines for the management and surveillance of TSC patients provide consensus guidance for delivery of best clinical care to individuals with TSC in the UK.

Quality of randomized clinical trials in juvenile idiopathic arthritis.

OBJECTIVES: We evaluated the quality of randomized clinical trials (RCTs) of therapy for juvenile idiopathic arthritis (JIA) using an individual component approach and assessed temporal changes. METHODS: A systematic review of the literature was performed to identify all RCTs involving exclusively JIA patients. Two investigators independently assessed the identified articles for six quality indicators: generation of allocation sequence, allocation concealment, masking, intention-to-treat (ITT) analysis, dropout rates and clearly stated primary outcome. RESULTS: Fifty-two RCTs involving JIA patients were assessed. Generation of allocation sequence was unclear in 79% of the studies. Reporting of allocation concealment was adequate in only one-third of the studies. Masking was adequate in 73%, inadequate in 19% and unclear in 8% of the reports. ITT analysis was employed in 37% of the reports. Per-protocol analysis was used in 40% and in 23% the method was unclear. Most of the reports (67%) had dropout rates < or = 20%. About half of the reports (n = 25) failed to show a significant effect of the experimental treatment. No significant associations were found between the study results and quality indicators. With the exception of adequate masking and dropout rate, all quality indicators showed a trend of improvement over the decades. CONCLUSIONS: The quality of RCTs in JIA based on the selected indicators was poor. Although there were some positive changes over time, the reporting and methodological quality of trials should be improved. New, more powerful and acceptable RCT designs should be developed in this patient population.