Validation of the Headache Impact Test (HIT-6™) across episodic and chronic migraine

Objective: The purpose of this study was to assess psychometric properties of the six-item Headache Impact Text (HIT-6™) across episodic and chronic migraine

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background<p></p> Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.<p></p> Methods<p></p> We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.<p></p> Results<p></p> Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.<p></p> Conclusions<p></p> We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

Differences in rate and medical indication of caesarean section between Germany and Japan

Background: There are growing concerns about the increasing rate of caesarean section (CS) worldwide. Various strategies have been implemented to reduce the proportion of CS to a reasonable level. Most research on medical indications for CS focuses on nationwide evaluations. Comparative research between different countries is sparse. The aim of this study was to evaluate differences in the rate and indications for CS between Japan and Germany in 2012 and 2013. Methods: Comparison of the overall rate and medical indications for CS in two cohort studies from Germany and Japan. We used data from the German Perinatal Survey and the Japan Environment and Children's Study (JECS). Results: We analyzed data of 1 335 150 participants from the German perinatal survey and of 62 533 participants from JECS and found significant differences between the two countries in CS rate (30.6% vs 20.6%) and main medical indications: cephalopelvic disproportion (3.2% vs 1.3%; OR: 2.4 [95% CI: 2.2–2.6]), fetal distress (7.3% vs 2.3%; OR: 3.4 [95%-CI: 3.2–3.6]), and past uterine surgery/repeat CS (8.4% vs 8.8%; OR: 0.9 [95%-CI: 0.9–1]). Conclusion: There are differences in the rate and medical indications for CS between Germany and Japan at the population level. Fetal distress was identified as a medical indication for CS more often Germany than in Japan. Considering the substantial diagnostic uncertainty of electronic fetal monitoring (EFM) as the major indicator for fetal distress, it would seem to be reasonable to rethink CS decision algorithms

Sharing clinical research data in the United States under the health insurance portability and accountability act and the privacy rule

Sharing of final research data from clinical research is an essential part of the scientific method. The U.S. National Institutes of Health require some grant applications to include plans for sharing final research data, which it defines as the factual materials necessary to document, support, and validate research findings. In the U.S., however, the Privacy Rule adopted under the Health Insurance Portability and Accountability Act impedes the sharing of final research data. In most situations, final research data may be shared only where all information that could possibly be used to identify the subject has been deleted, or where the subject has given authorization for specific research, or an Institutional Review Board has granted a waiver

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

Shear friction strength of monolithic concrete interfaces

YesThis paper presents an integrated model for shear friction strength of monolithic concrete interfaces derived from the upper-bound theorem of concrete plasticity. The model accounts for the effects of applied axial stresses and transverse reinforcement on the shear friction action at interfacial shear cracks. Simple equations were also developed to generalize the effectiveness factor for compression, ratio of effective tensile to compressive strengths and angle of concrete friction. The reliability of the proposed model was then verified through comparisons with previous empirical equations and 103 push-off test specimens compiled from different sources in the literature. The previous equations considerably underestimate the concrete shear transfer capacity and the underestimation is notable for the interfaces subjected to additional axial stresses. The proposed model provides superior accuracy in predicting the shear friction strength, resulting in a mean between experimental and predicted friction strengths of 0.97 and least scatter. Moreover, the proposed model has consistent trends with test results in evaluating the effect of various parameters on the shear friction strength

Clinical practice. Diagnosis and treatment of cow’s milk allergy

Introduction Cow's milk allergy (CMA) is thought to affect 2-3% of infants. The signs and symptoms are nonspecific and may be difficult to objectify, and as the diagnosis requires cow's milk elimination followed by challenge, often, children are considered cow's milk allergic without proven diagnosis. Diagnosis Because of the consequences, a correct diagnosis of CMA is pivotal. Open challenges tend to overestimate the number of children with CMA. The only reliable way to diagnose CMA is by double-blind, placebo-controlled challenge (DBPCFC). Therapy At present, the only proven treatment consists of elimination of cow's milk protein from the child's diet and the introduction of formulas based on extensively hydrolysed whey protein or casein; amino acid-based formula is rarely indicated. The majority of children will regain tolerance to cow's milk within the first 5 years of life. Conclusions Open challenges can be used to reject CMA, but for adequate diagnosis, DBPCFC is mandatory. In most children, CMA can be adequately treated with extensively hydrolysed whey protein or casein formulas

Trends in Deceased Organ Donation and Utilization in Korea: 2000-2009

Continuous efforts have been made by the organ donation and transplantation community in Korea to increase organ donation by the deceased. The authors detailed trends of organ donation and utilization over the past 10 yr using data provided by the KONOS. The yearly number of deceased donors has grown gradually since 2003. The number and percentage of old donors (≥50 yr) and donors dying from intracranial hemorrhage has increased continuously. Therefore, the percentage of standard criteria donors (SCD) has been declining significantly, from 94% in 2000 to 79.2% in 2009. The number of organs transplanted per donor (OTPD) has also declined slightly since 2007, from 3.28 in 2007 to 2.95 in 2009. This decline may be attributable to increases in the number and percentage of extended criteria donors (ECD) and donors after cardiac death (DCD), since the OTPD was 2.25 for DCD, 2.5 for ECD, and 3.09 for SCD in 2009. In summary, the makeup of donors has changed significantly. There is an urgent need for establishment of an institutional framework including an independent organ procurement organization and for improvement for the National Transplant Act to increase deceased donor pool and to optimize management of ECD and DCD

Further Increase of Vancomycin-Resistant Enterococcus faecium, Amikacin- and Fluoroquinolone-Resistant Klebsiella pneumoniae, and Imipenem-Resistant Acinetobacter spp. in Korea: 2003 KONSAR Surveillance

Monitoring temporal trends of antimicrobial resistance can provide useful information for the empirical selection of antimicrobial agents to treat infected patients and for the control of nosocomial infections. In this study, we analyzed antimicrobial resistance of clinically relevant bacteria in 2003 at Korean hospitals and at a commercial laboratory. The following organism-antimicrobial agent resistance combinations were very prevalent: oxacillin-resistant Staphylococcus aureus (68%), expanded-spectrum cephalosporin-resistant Klebsiella pneumoniae (25%), and fluoroquinolone-resistant Escherichia coli (33%), Acinetobacter spp. (58%), and Pseudomonas aeruginosa (40%). Moreover, gradual increases in vancomycin-resistant Enterococcus faecium (20%), cefoxitin-resistant E. coli (10%) and K. pneumoniae (23%), and imipenem-resistant P. aeruginosa (20%) and Acinetobacter spp. (13%) were also observed. The resistance rates of Acinetobacter spp. to most antimicrobial agents at hospitals and at the commercial laboratory were similar. Among the Acinetobacter spp. isolated at a tertiary-care hospital, 46.2% were multidrug-resistant to 9-12 of 13 antimicrobial agents, and 18.3% were panresistant. The exclusion of duplicate isolates at a tertiary-care hospital significantly lowered the proportion of oxacillin-resistant S. aureus, vancomycin-resistant E. faecium, and fluoroquinolone-resistant E. coli

Collegial nests can Foster Critical Thinking, Innovative Ideas, and Scientific Progress.

How can management and strategy scholars organize to generate more productive, more innovative, and more impactful research? With appropriate cultures and leaders, small and egalitarian discussion groups that we call “collegial nests” can become powerful generators of innovative ideas and creators of extraordinary scholars. Collegial nests need cultures that free participants to think critically, to cherish new viewpoints, and to speak freely without fear of ridicule. They also need leaders who model such cultures and facilitate frequent discussions. Two case examples illustrate how productive collegial nests can create better science and better scientists. To generate scientific innovation and progress on a large scale, many autonomous groups tackling related issues are desirable. Modern communication technology is making it feasible for groups to operate over large distances and to coordinate with each other at very low cost. Collegial nests offer greater potential for enhancing scholarly productivity and innovation than do attempts to regulate scholarship via hierarchical structures. Multiplicity can lower the probability of wasting resources on low-yield paths, egalitarian control can reduce the influence of vested interests, and a combination of shared goals and partial autonomy can integrate enthusiasm with sensible risk taking