The Reflection on the Management of Toxic Epidermal Necrolysis in the Community Setting: An Internist\u27s Perspective

Toxic epidermal necrolysis (TEN) is a dermatological emergency that is often associated with high mortality. It is differentiated from Stevens-Johnson syndrome (SJS) based on the percentage of the total body surface area affected. There has been an established correlation with certain medications that could trigger the development of such a devastating disease. Despite numerous research studies conducted on aspects of this disease entity, TEN remains foreign to many general Internists situated in a community setting due to the extremely low disease prevalence that leads to a lack of overall experience and medical resources in dealing with this medical condition. Thus, we outlined several important management aspects of TEN/SJS that an Internist should be aware of in order to assist in prompt clinical decision making and prognosis forecasting as well as deliver effective family communication

Hyaluronan and self-assembling peptides as building blocks to reconstruct the extracellular environment in skin tissue

Funding for this study was provided by the Portuguese Foundation for Science and Technology (FCT, grant PTDC/EBB-BIO/114523/2009). D. S. Ferreira gratefully acknowledges FCT for a PhD scholarship (SFRH/BD/44977/2008

“It’s hard to tell”. The challenges of scoring patients on standardised outcome measures by multidisciplinary teams: a case study of Neurorehabilitation

Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management

Requirements for NuMA in maintenance and establishment of mammalian spindle poles

Microtubules of the mitotic spindle in mammalian somatic cells are focused at spindle poles, a process thought to include direct capture by astral microtubules of kinetochores and/or noncentrosomally nucleated microtubule bundles. By construction and analysis of a conditional loss of mitotic function allele of the nuclear mitotic apparatus (NuMA) protein in mice and cultured primary cells, we demonstrate that NuMA is an essential mitotic component with distinct contributions to the establishment and maintenance of focused spindle poles. When mitotic NuMA function is disrupted, centrosomes provide initial focusing activity, but continued centrosome attachment to spindle fibers under tension is defective, and the maintenance of focused kinetochore fibers at spindle poles throughout mitosis is prevented. Without centrosomes and NuMA, initial establishment of spindle microtubule focusing completely fails. Thus, NuMA is a defining feature of the mammalian spindle pole and functions as an essential tether linking bulk microtubules of the spindle to centrosomes

Functional central spindle assembly requires de novo microtubule generation in the interchromosomal region during anaphase

The augmin protein complex nucleates noncentrosomal microtubules during anaphase to promote completion of cell division

Center of Excellence in Research Reporting in Neurosurgery - Diagnostic Ontology

Motivation: Evidence-based medicine (EBM), in the field of neurosurgery, relies on diagnostic studies since Randomized Controlled Trials (RCTs) are uncommon. However, diagnostic study reporting is less standardized which increases the difficulty in reliably aggregating results. Although there have been several initiatives to standardize reporting, they have shown to be sub-optimal. Additionally, there is no central repository for storing and retrieving related articles. Results: In our approach we formulate a computational diagnostic ontology containing 91 elements, including classes and sub-classes, which are required to conduct Systematic Reviews - Meta Analysis (SR-MA) for diagnostic studies, which will assist in standardized reporting of diagnostic articles. SR-MA are studies that aggregate several studies to come to one conclusion for a particular research question. We also report high percentage of agreement among five observers as a result of the interobserver agreement test that we conducted among them to annotate 13 articles using the diagnostic ontology. Moreover, we extend our existing repository CERR-N to include diagnostic studies. Availability: The ontology is available for download as an.owl file at: http://bioportal.bioontology.org/ontologies/3013

Lessons and implications from a mass immunization campaign in squatter settlements of Karachi, Pakistan: an experience from a cluster-randomized double-blinded vaccine trial [NCT00125047]

OBJECTIVE: To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. METHODS: A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. RESULTS: The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial when the code is broken. Throughout the vaccination campaign safe injection practices were maintained and the cold chain was not interrupted. Mass vaccination in slums had good acceptance. Because populations in such areas are highly mobile, settlement conditions could affect coverage. Systemic reactions were uncommon and local reactions were mild and transient. Close community involvement was pivotal for information dissemination and immunization coverage. CONCLUSION: This vaccine strategy described together with other information that will soon be available in the area (cost/effectiveness, vaccine delivery costs, etc) will make typhoid fever control become a reality in the near future

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C