Development of a risk model for adverse drug events in the elderly

The aim of this study was to develop a predictive model for adverse drug events (ADEs) in elderly patients. Socio-demographic and medical data were collected from chart reviews, computerised information and a patient interview, for a population of 929 elderly patients (aged greater than or equal to 65 years) whose admission to the Waveney/B raid Valley Hospital in Northern Ireland was not scheduled. A further 204 patients formed a validation group. An ADE score was assigned to each patient using a modified Naranjo algorithm scoring system. The ADE scores ranged from 0 to 8. For the purposes of developing a risk model, scores of 4 or more were considered to constitute a high risk of an ADE.

Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration: One-Year Findings from the IVAN Randomized Trial.

Purpose
To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD).

Design
Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560).

Participants
People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart.

Methods
We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review.

Main Outcome Measures
The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs.

Results
Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001).

Conclusions
The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety.

Financial Disclosure(s)
Proprietary or commercial disclosures may be found after the references.

Improved description of chemical barriers with generalized gradient approximations (GGAs) and meta-GGAs

The performance of exchange and correlation (xc) functionals of the generalized gradient approximation (GGA) type and of the meta-GGA type in the calculation of chemical reactions is related to topological features of the electron density which, in turn, are connected to the orbital structure of chemical bonds within the Kohn-Sham (KS) theory. Seventeen GGA and meta-GGA xc functionals are assessed for 15 hydrogen abstraction reactions and 3 symmetrical S(N)2 reactions. Systems that are problematic for standard GGAs characteristically have enhanced values of the dimensionless gradient argument s(sigma)(2) with local maxima in the bonding region. The origin of this topological feature is the occupation of valence KS orbitals with an antibonding or essentially nonbonding character. The local enhancement of s(sigma)(2) yields too negative exchange-correlation energies with standard GGAs for the transition state of the S(N)2 reaction, which leads to the reduced calculated reaction barriers. The unwarranted localization of the effective xc hole of the standard GGAs, i.e., the nondynamical correlation that is built into them but is spurious in this case, wields its effect by their s(sigma)(2) dependence. Barriers are improved for xc functionals with the exchange functional OPTX as x component, which has a modified dependence on s(sigma)(2). Standard GGAs also underestimate the barriers for the hydrogen abstraction reactions. In this case the barriers are improved by correlation functionals, such as the Laplacian-dependent (LAP3) functional, which has a modified dependence on the Coulomb correlation of the opposite- and like-spin electrons. The best overall performance is established for the combination OLAP3 of OPTX and LAP3.

Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system

Colistin resistance is rare in Acinetobacter baumannii, and little is known about its mechanism. We investigated the role of PmrCAB in this trait, using (i) resistant and susceptible clinical strains, (ii) laboratory-selected mutants of the type strain ATCC 19606 and of the clinical isolate ABRIM, and (iii) a susceptible/resistant pair of isogenic clinical isolates, Ab15/133 and Ab15/132, isolated from the same patient. pmrAB sequences in all the colistin-susceptible isolates were identical to reference sequences, whereas resistant clinical isolates harbored one or two amino acid replacements variously located in PmrB. Single substitutions in PmrB were also found in resistant mutants of strains ATCC 19606 and ABRIM and in the resistant clinical isolate Ab15/132. No mutations in PmrA or PmrC were found. Reverse transcriptase (RT)-PCR identified increased expression of pmrA (4- to 13-fold), pmrB (2- to 7-fold), and pmrC (1- to 3-fold) in resistant versus susceptible organisms. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry showed the addition of phosphoethanolamine to the hepta-acylated form of lipid A in the resistant variants and in strain ATCC 19606 grown under low-Mg induction conditions. pmrB gene knockout mutants of the colistin-resistant ATCC 19606 derivative showed >100-fold increased susceptibility to colistin and 5-fold decreased expression of pmrC; they also lacked the addition of phosphoethanolamine to lipid A. We conclude that the development of a moderate level of colistin resistance in A. baumannii requires distinct genetic events, including (i) at least one point mutation in pmrB, (ii) upregulation of pmrAB, and (iii) expression of pmrC, which lead to addition of phosphoethanolamine to lipid A. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Access to medical records for research purposes:Varying perceptions across research ethics boards

Introduction: Variation across research ethics boards (REBs) in conditions placed on access to medical records for research purposes raises concerns around negative impacts on research quality and on human subject protection, including privacy. Aim: To study variation in REB consent requirements for retrospective chart review and who may have access to the medical record for data abstraction. Methods: Thirty 90-min face-to-face interviews were conducted with REB chairs and administrators affiliated with faculties of medicine in Canadian universities, using structured questions around a case study with open-ended responses. Interviews were recorded, transcribed and coded manually. Results: Fourteen sites (47%) required individual patient consent for the study to proceed as proposed. Three (10%) indicated that their response would depend on how potentially identifying variables would be managed. Eleven sites (38%) did not require consent. Two (7%) suggested a notification and opt-out process. Most stated that consent would be required if identifiable information was being abstracted from the record. Among those not requiring consent, there was substantial variation in recognising that the abstracted information could potentially indirectly re-identify individuals. Concern over access to medical records by an outside individual was also associated with requirement for consent. Eighteen sites (60%) required full committee review. Sixteen (53%) allowed an external research assistant to abstract information from the health record. Conclusions: Large variation was found across sites in the requirement for consent for research involving access to medical records. REBs need training in best practices for protecting privacy and confidentiality in health research. A forum for REB chairs to confidentially share concerns and decisions about specific studies could also reduce variation in decisions.

Cavitary melanoma of the ciliary body. A study of eight cases

Purpose: The authors present the unique clinical features of cavitary uveal melanoma. Design: Retrospective chart review. Participants: Eight patients with cavitary uveal melanoma. Main Outcome Measures: The clinical, ultrasonographic, and histopathologic features of eight patients with cavitary melanoma of the ciliary body were studied. Results: In all eyes there was a brown ciliary body mass that blocked transmission of light on trans-scleral transillumination. Ocular ultrasonography revealed a large, single hollow cavity (unilocular 'pseudocyst') in five cases and multiple hollow cavities (multilocular 'pseudocyst') in three cases. The cavity occupied a mean of 55% of the entire mass thickness (range, 31%-79%). In five cases, a basal uveal mass was noted on ultrasonography. Four patients underwent tumor resection; one had enucleation, and three had 1251 radioactive plaque treatment. In the five cases confirmed histopathologically, the cavitation was empty, contained erythrocytes, serous fluid, and/or pigment-laden macrophages. In no case was the cavity lined by necrotic tumor, endothelial cells, or epithelial cells. Conclusion: Ciliary body melanoma can develop an intralesional cavity resembling an intraocular cyst. The presence of a solid mass at the base and a thick wall surrounding the cavity can assist in the differentiation of cavitary melanoma from benign cyst.

The quality of reporting of diagnostic accuracy studies published in ophthalmic journals

Aim: To evaluate the quality of reporting of all diagnostic studies published in five major ophthalmic journals in the year 2002 using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative parameters. Methods: Manual searching was used to identify diagnostic studies published in 2002 in five leading ophthalmic journals, the American Journal of Ophthalmology (AJO), Archives of Ophthalmology (Archives), British Journal of Ophthalmology (BJO), Investigative Ophthalmology and Visual Science (IOVS), and Ophthalmology. The STARD checklist of 25 items and flow chart was used to evaluate the quality of each publication. Results: A total of 16 publications were included (AJO = 5, Archives = 1, BJO = 2, IOVS = 2, and Ophthalmology = 6). More than half of the studies (n = 9) were related to glaucoma diagnosis. Other specialties included retina (n = 4) cornea (n = 2), and neuro-ophthalmology (n = 1). The most common description of diagnostic accuracy was sensitivity and specificity values, published in 13 articles. The number of fully reported items in evaluated studies ranged from eight to 19. Seven studies reported more than 50% of the STARD items. Conclusions: The current standards of reporting of diagnostic accuracy tests are highly variable. The STARD initiative may be a useful tool for appraising the strengths and weaknesses of diagnostic accuracy studies.

Improved principal component monitoring using the local approach

This paper shows that current multivariate statistical monitoring technology may not detect incipient changes in the variable covariance structure nor changes in the geometry of the underlying variable decomposition. To overcome these deficiencies, the local approach is incorporated into the multivariate statistical monitoring framework to define two new univariate statistics for fault detection. Fault isolation is achieved by constructing a fault diagnosis chart which reveals changes in the covariance structure resulting from the presence of a fault. A theoretical analysis is presented and the proposed monitoring approach is exemplified using application studies involving recorded data from two complex industrial processes. © 2007 Elsevier Ltd. All rights reserved.

Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age

Objective

To examine whether early inflammation is related to cortisol levels at 18 months corrected age (CA) in children born very preterm.

Study Design

Infants born ≤ 32 weeks gestational age were recruited in the NICU, and placental histopathology, MRI, and chart review were obtained. At 18 months CA developmental assessment and collection of 3 salivary cortisol samples were carried out. Generalized least squares was used to analyze data from 85 infants providing 222 cortisol samples.

Results

Infants exposed to chorioamnionitis with funisitis had a significantly different pattern of cortisol across the samples compared to infants with chorioamnionitis alone or no prenatal inflammation (F[4,139] = 7.3996, P <.0001). Postnatal infections, necrotizing enterocolitis and chronic lung disease were not significantly associated with the cortisol pattern at 18 months CA.

Conclusion

In children born very preterm, prenatal inflammatory stress may contribute to altered programming of the HPA axis.

Keywords: preterm, chorioamnionitis, funisitis, premature infants, hypothalamic-pituitary-adrenal axis, infection, cortisol, stress

TEXTILE TECHNOLOGIES IN CONCRETE ENVIRONMENTS."

Girli Concrete is a cross disciplinary funded research project based in the University of Ulster involving a textile designer/ researcher, an architect/ academic and a concrete manufacturing firm.
Girli Concrete brings together concrete and textile technologies, testing ideas of
concrete as textile and textile as structure. It challenges the perception of textiles as only the ‘dressing’ to structure and instead integrates textile technologies into the products of building products. Girli Concrete uses ‘low tech’ methods of wet and dry concrete casting in combination with ‘high tech’ textile methods using laser cutting, etching, flocking and digital printing. Whilst we have been inspired by recent print and imprint techniques in architectural cladding, Girli Concrete is generated within the depth of the concrete’s cement paste “skin”, bringing the trades and crafts of both industries together with innovative results.
Architecture and Textiles have an odd, somewhat unresolved relationship. Confined to a subservient role in architecture, textiles exist chiefly within the categories of soft furnishings and interior design. Girli Concrete aims to mainstream tactility in the production of built environment products, raising the human and environmental interface to the same specification level as the technical. This paper will chart:
The background and wider theoretical concerns to the project.
The development of Girli Concrete, highlighting the areas where craft becomes
art and art becomes science in the combination of textile and concrete
technologies.
The challenges of identifying funding to support such combination technologies,
working methods and philosophies.
The challenges of generating and sustaining practice within an academic
research environment
The outcomes to date

Algorithms for Self-Healing Networks

Many modern networks are \emph{reconfigurable}, in the sense that the topology of the network can be changed by the nodes in the network. For example, peer-to-peer, wireless and ad-hoc networks are reconfigurable. More generally, many social networks, such as a company's organizational chart; infrastructure networks, such as an airline's transportation network; and biological networks, such as the human brain, are also reconfigurable. Modern reconfigurable networks have a complexity unprecedented in the history of engineering, resembling more a dynamic and evolving living animal rather than a structure of steel designed from a blueprint. Unfortunately, our mathematical and algorithmic tools have not yet developed enough to handle this complexity and fully exploit the flexibility of these networks. We believe that it is no longer possible to build networks that are scalable and never have node failures. Instead, these networks should be able to admit small, and maybe, periodic failures and still recover like skin heals from a cut. This process, where the network can recover itself by maintaining key invariants in response to attack by a powerful adversary is what we call \emph{self-healing}. Here, we present several fast and provably good distributed algorithms for self-healing in reconfigurable dynamic networks. Each of these algorithms have different properties, a different set of gaurantees and limitations. We also discuss future directions and theoretical questions we would like to answer. %in the final dissertation that this document is proposed to lead to.

'Big, strong and healthy'. Young children's identification of food and drink that contribute to healthy growth

Growing awareness of the importance of healthy diet in early childhood makes it important to chart the development of children's understanding of food and drink. This study aimed to document young children's evaluation of food and drink as healthy, and to explore relationships with socioeconomic status, family eating habits, and children's television viewing. Data were gathered from children aged 3-5. years (. n=. 172) in diverse socioeconomic settings in Ireland, and from their parents. Results demonstrated that children had very high levels of ability to identify healthy foods as important for growth and health, but considerably less ability to reject unhealthy items, although knowledge of these increased significantly between ages 3 and 5. Awareness of which foods were healthy, and which foods were not, was not related to family socioeconomic status, parent or child home eating habits, or children's television viewing. Results highlighted the importance of examining young children's response patterns, as many of the youngest showed a consistent 'yes bias'; however, after excluding these responses, the significant findings remained. Findings suggest it is important to teach children about less healthy foods in the preschool years. © 2013 Elsevier Ltd.

Uniformity of visual acuity measures in published studies

PURPOSE. To investigate the methods used in contemporary ophthalmic literature to designate visual acuity (VA). METHODS. Papers in all 2005 editions of five ophthalmic journals were considered. Papers were included if (1) VA, vision, or visual function was mentioned in the abstract and (2) if the study involved age-related macular degeneration, cataract, or refractive surgery. If a paper was selected on the basis of its abstract, the full text of the paper was examined for information on the method of refractive correction during VA testing, type of chart used to measure VA, specifics concerning chart features, testing protocols, and data analysis and means of expressing VA in results. RESULTS. One hundred twenty-eight papers were included. The most common type of charts used were described as logMAR-based. Although most (89.8%) of the studies reported on the method of refractive correction during VA testing, only 58.6% gave the chart design, and less than 12% gave any information whatsoever on chart features or measurement procedures used. CONCLUSIONS. The methods used and the approach to analysis were rarely described in sufficient detail to allow others to replicate the study being reported. Sufficient detail should be given on VA measurement to enable others to duplicate the research. The authors suggest that charts adhering to Bailey-Lovie design principles always be used to measure vision in prospective studies and their use encouraged in clinical settings. The distinction between the terms logMAR, an acuity notation, and Bailey-Lovie or ETDRS as chart types should be adhered to more strictly. Copyright © Association for Research in Vision and Ophthalmology.

Optical coherence tomography for the diagnosis of neovascular age-related macular degeneration: a systematic review

The purpose is to study the diagnostic performance of optical coherence tomography (OCT) and alternative diagnostic tests for neovascular age-related macular degeneration (nAMD). Methods employed are as follows:systematic review and meta-analysis; Index test: OCT including time-domain (TD-OCT) and the most recently developed spectral domain (SD-OCT); comparator tests: visual acuity, clinical evaluation (slit lamp), Amsler chart, colour fundus photographs, infra-red reflectance, red-free images/blue reflectance, fundus autofluorescence imaging (FAF), indocyanine green angiography (ICGA), preferential hyperacuity perimetry (PHP), and microperimetry; reference standard: fundus fluorescein angiography. Databases searched included MEDLINE, MEDLINE In Process, EMBASE, Biosis, SCI, the Cochrane Library, DARE, MEDION, and HTA database. Last literature searches: March 2013. Risk of bias assessed using QUADAS-2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic (HSROC) curves. Twenty-two studies (2 abstracts and 20 articles) enrolling 2124 participants were identified, reporting TD-OCT (12 studies), SD-OCT (1 study), ICGA (8 studies), PHP (3 studies), Amsler grid, colour fundus photography and FAF (1 study each). Most studies were considered to have a high risk of bias in the patient selection (55%, 11/20), and flow and timing (40%, 8/20) domains. In a meta-analysis of TD-OCT studies, sensitivity and specificity (95% CI) were 88% (46–98%) and 78% (64–88%), respectively. There was insufficient information to undertake meta-analysis for other tests. TD-OCT is a sensitive test for detecting nAMD, although specificity was only moderate. Data on SD-OCT are sparse. Diagnosis of nAMD should not rely solely on OCT.