Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data

Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo

Specific MRI Abnormalities Reveal Severe Perrault Syndrome due to CLPP Defects

In establishing a genetic diagnosis in heterogeneous neurological disease, clinical characterization and whole exome sequencing (WES) go hand-in-hand. Clinical data are essential, not only to guide WES variant selection and define the clinical severity of a genetic defect but also to identify other patients with defects in the same gene. In an infant patient with sensorineural hearing loss, psychomotor retardation, and epilepsy, WES resulted in identification of a novel homozygous CLPP frameshift mutation (c.21delA). Based on the gene defect and clinical symptoms, the diagnosis Perrault syndrome type 3 (PRLTS3) was established. The patient's brain-MRI revealed specific abnormalities of the subcortical and deep cerebral white matter and the middle blade of the corpus callosum, which was used to identify similar patients in the Amsterdam brain-MRI database, containing over 3000 unclassified leukoencephalopathy cases. In three unrelated patients with similar MRI abnormalities the CLPP gene was sequenced, and in two of them novel missense mutations were identified together with a large deletion that covered part of the CLPP gene on the other allele. The severe neurological and MRI abnormalities in these young patients were due to the drastic impact of the CLPP mutations, correlating with the variation in clinical manifestations among previously reported patients. Our data show that similarity in brain-MRI patterns can be used to identify novel PRLTS3 patients, especially during early disease stages, when only part of the disease manifestations are present. This seems especially applicable to the severely affected cases in which CLPP function is drastically affected and MRI abnormalities are pronounce

Genetical genomics: spotlight on QTL hotspots

No abstract available

The Cochrane Skin Group: a vanguard for developing and promoting evidence-based dermatology

Aim The Cochrane Skin Group (CSG) is part of the international Cochrane Collaboration (http://www.cochrane.org/). The CSG prepares, maintains and disseminates high quality evidence-based summaries on the prevention, diagnosis and treatment of skin diseases. We present a synopsis of the history, scope and priorities of the CSG. In addition, we report outcomes of CSG reviews and critically assess clinical value. Methods Descriptive analysis of systematic reviews published by the CSG since its inception including output, impact factor, associated methodological studies, and influence in clinical guidelines, promoting patient and public engagement and in triggering new primary research. Results The CSG started in 1997, and has published 61 reviews, 34 protocols and 31 registered titles by August 2013. The CSG scope includes 1000 skin diseases; 80% of reviews cover the top ten diagnoses and 40% of reviews provide clear guidance for clinical practice. CSG reviews had an impact factor of 6.1 in 2011 which places it alongside top dermatology journals. CSG reviews are typically broad in focus and have been shown to be of better quality than non-Cochrane reviews. They are highly cited in clinical guidelines. Several reviews have identified evidence gaps that have led to better primary research. Conclusions The CSG has emerged as a vanguard of evidence-based dermatology by growing a community interested in applying best external evidence to the care of skin patients and by identifying topics for research. CSG reviews are high impact, clinically relevant and have tangibly influenced international dermatology clinical practice guidelines and new research

Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

Angiographically borderline left main coronary artery lesions: correlation of transthoracic doppler echocardiography and intravascular ultrasound: a pilot study

<p>Abstract</p> <p>Background</p> <p>the clinical decision making could be difficult in patients with borderline lesions (visually assessed stenosis severity of 30 to 50%) of the left main coronary artery (LM). The aim of the study was to evaluate the relationship between transthoracic Doppler (TTDE) peak diastolic flow velocity (PDV) and intravascular ultrasound (IVUS) measurements in the assessment of angiographically borderline LM lesions.</p> <p>Methods</p> <p>27 patients (mean age 64 ± 8 years, 21 males) with borderline LM stenosis referred for IVUS examination were included in the study. We performed standard IVUS with minimal lumen area (MLA) and plaque burden (PB) measurement and routine quantitative coronary angiography (QCA) with diameter stenosis (%DS) and area stenosis (%AS) assessment in all. During TTDE, resting PDV was measured in the LM.</p> <p>Results</p> <p>interpretable Doppler signal could be obtained in 24 patients (88% feasibility); therefore these patients entered the final analysis. MLA was 7.1 ± 2.7 mm². TTDE measured PDV correlated significantly with IVUS-derived MLA (r = -0.46, p < 0.05) and plaque burden (r = 0.51, p < 0.05). Using a velocity cut-off of 112 cm/sec TTDE showed a 92% sensitivity and 62% specificity to identify IVUS-significant (MLA < 6 mm²) LM stenosis.</p> <p>Conclusion</p> <p>In angiographically borderline LM disease, resting PDV from transthoracic echocardiography is increased in presence of increased plaque burden by IVUS. TTDE evaluation might be a useful adjunct to other invasive and non-invasive methods in the assessment of borderline LM lesions. Further, large scale studies are needed to establish the exact cut-off value of PDV for routine clinical application.</p

Selection of eligible participants for screening for lung cancer using primary care data

Lung cancer screening is effective if offered to people at increased risk of the disease. Currently, direct contact with potential participants is required for evaluating risk. A way to reduce the number of ineligible people contacted might be to apply risk-prediction models directly to digital primary care data, but model performance in this setting is unknown.Method: The Clinical Practice Research Datalink, a computerised, longitudinal primary care database, was used to evaluate the LLPv2 and PLCOm2012 models. Lung cancer occurrence over 5-6 years was measured in ever-smokers aged 50-80 years and compared with 5-year (LLPv2) and 6-year (PLCOm2012) predicted risk. Results: Over 5 and 6 years, 7,123 and 7,876 lung cancers occurred respectively from a cohort of 842,109 ever smokers. After recalibration, LLPV2 produced a c-statistic of 0.700 (0.694-0.710) but mean predicted risk was over-estimated (predicted: 4.61%, actual: 0.9%). PLCOm2012 showed similar performance (c-statistic: 0.679 (0.673–0.685), predicted risk: 3.76%. Applying risk-thresholds of 1% (LLPv2) and 0.15% (PLCOm2012), would avoid contacting 42.7% and 27.4% of ever-smokers who did not develop lung cancer for screening eligibility assessment, at the cost of missing 15.6% and 11.4% of lung cancers.Conclusion: Risk-prediction models showed only moderate discrimination when applied to routinely collected primary care data, which may be explained by quality and completeness of data. However, they may substantially reduce the number of people for initial evaluation of screening eligibility, at the cost of missing some lung cancers. Further work is needed to establish whether newer models have improved performance in primary care data

Identity Drift:The Multivocality of Ethical Identity in Islamic Financial Institution

In today’s neo-liberalist world, Islamic financial institutions (IFIs) face many difficulties combining contemporary financial thinking with Islamic, faith-based principles, on which their day-to-day operations ought to be based. Hence, IFI are likely to experience shifts/changes in organizational and ethical identity due to tensions that the combination of these principles invokes. We present an in-depth case study that focuses on these shifts in a major European based IFI across a 14-year period. We conceptualize identity change as drift, highlighting the multivocal nature of identity construction. The ethico-faith principles that were meant to serve as living codes of ethics guiding the IFI’s organizational culture, operational processes, and strategy formation turned out to mainly have been discursively rationalized to respond to regulatory, market and institutional imperatives. The company is aware that it needs to engage in a continuous dialogue with those who set these requirements. Its ethico-faith principles may consequently be adapted quite radically, especially in periods of turmoil and takeover, as we show across the analysed time period. The paper provides valuable insights for faith-inspired organizations to reflect on the extent to which they wish to engage in the discursive justification and legitimization of current market hegemonies, whilst they actively encourage their managers to behave ethically as well