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.

Clinical relevance of the ESKAPE pathogens.

In recent years, the Infectious Diseases Society of America has highlighted a faction of antibiotic-resistant bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) - acronymically dubbed 'the ESKAPE pathogens' - capable of 'escaping' the biocidal action of antibiotics and mutually representing new paradigms in pathogenesis, transmission and resistance. This review aims to consolidate clinically relevant background information on the ESKAPE pathogens and provide a contemporary summary of bacterial resistance, alongside pertinent microbiological considerations necessary to face the mounting threat of antimicrobial resistance.

Biomonitoring aquatic environmental quality in a marine protected area: A biomarker approach

The main aims of the present study, conducted in the framework of the MONIQUA-Egadi Scientific Project, were twofold: first, to make the first step in the development and validation of an ecotoxicological approach for the assessment of marine pollution in coastal environments on the basis of a set of biomarker responses in new sentinel species; and second, to obtain preliminary information on environmental quality in an Italian marine protected area, the Egadi Islands (Sicily). Several cytochrome P450-dependent mixed-function oxidase activities were measured in the following sentinel species: rainbow wrasse Coris julis, gastropod limpet Patella caerulea, and sea urchin Paracentrotus lividus. The results suggest that specimens from the Favignana Harbor may be exposed to P450 inducers, whereas most of the other sites seem to share similar environmental quality. The proposed approach has potential for assessment of environmental quality in marine protected areas.

Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial

Background: Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration. The Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial was designed to compare these drugs and different regimens. Here, we report the findings at the prespecified 2-year timepoint. Methods: In a multicentre, 2×2 factorial, non-inferiority randomised trial, we enrolled adults aged at least 50 years with active, previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity (BCVA) of at least 25 letters from 23 hospitals in the UK. Participants were randomly assigned (1:1:1:1) to intravitreal injections of ranibizumab (0·5 mg) or bevacizumab (1·25 mg) in continuous (every month) or discontinuous (as needed) regimens, with monthly review. Study participants and clinical assessors were masked to drug allocation. Allocation to continuous or discontinuous treatment was masked up to 3 months, at which point investigators and participants were unmasked. The primary outcome was BCVA at 2 years, with a prespecified non-inferiority limit of 3·5 letters. The primary safety outcome was arterial thrombotic event or hospital admission for heart failure. Analyses were by modified intention to treat. This trial is registered, number ISRCTN92166560. Findings: Between March 27, 2008, and Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in continuous regimen, 137 ranibizumab in discontinuous regimen, 127 bevacizumab in continuous regimen, and 127 bevacizumab in discontinuous regimen. For BCVA, bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference -1·37 letters, 95% CI -3·75 to 1·01; p=0·26). Discontinuous treatment was neither non-inferior nor inferior to continuous treatment (-1·63 letters, -4·01 to 0·75; p=0·18). Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab (20 [6%] of 314 participants) and bevacizumab (12 [4%] of 296; odds ratio [OR] 1·69, 95% CI 0·80-3·57; p=0·16), or those given continuous (12 [4%] of 308) and discontinuous treatment (20 [7%] of 302; 0·56, 0·27-1·19; p=0·13). Mortality was lower with continuous than discontinuous treatment (OR 0·47, 95% CI 0·22-1·03; p=0·05), but did not differ by drug group (0·96, 0·46-2·02; p=0·91). Interpretation: Ranibizumab and bevacizumab have similar efficacy. Reduction in the frequency of retreatment resulted in a small loss of efficacy irrespective of drug. Safety was worse when treatment was administered discontinuously. These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought.

Morphometric analysis of corneal endothelial giant cells in normal and traumatized corneas

Corneal endothelial cells from normal and traumatized human, primate, cat and rabbit eyes were studied by specular microscopy. Morphometric analysis was performed on micrographs of corneal endothelium using a semi-automated image analysis system. The results showed that under normal conditions the corneal endothelium of all four species exhibit major morphological similarities (mean cell areas: human 317 +/- 32 microns 2, primate 246 +/- 22 microns2, cat 357 +/- 25 microns 2, rabbit 308 +/- 35 microns 2). The normal corneal endothelium in man was found to be more polymegethous than that of the other species. Trauma to cat, primate and human corneas resulted in a long-term reduction in endothelial cell density and enhanced polymegethism. In contrast, the reparative response of the rabbit ensured the reformation of an essentially normal monolayer following injury. Endothelial giant cells were a normal inclusion in the rabbit corneal endothelium but were only significant in cat, primate and man following trauma. The presence of corneal endothelial giant cells in amitotic corneas may therefore represent a compensatory response in the absence of mitotic potential.

Disordered vascular compliance in haemochromatosis

Background: A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk.

Aims: To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls.

Methods: Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured.

Results: Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 lmol/L, p = 0.011), retinol (1.17 vs. 1.81 lmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 lmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32).

Conclusions: Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.

Prevalence of human papillomavirus in women attending cervical screening in the UK and Ireland:New data from northern Ireland and a systematic review and meta-analysis

There is substantial international variation in human papillomavirus (HPV) prevalence; this study details the first report from Northern Ireland and additionally provides a systematic review and meta-analysis pooling the prevalence of high-risk (HR-HPV) subtypes among women with normal cytology in the UK and Ireland. Between February and December 2009, routine liquid based cytology (LBC) samples were collected for HPV detection (Roche Cobas® 4800 [PCR]) among unselected women attending for cervical cytology testing. Four electronic databases, including MEDLINE, were then searched from their inception till April 2011. A random effects meta-analysis was used to calculate a pooled HR-HPV prevalence and associated 95% confidence intervals (CI). 5,712 women, mean age 39 years (±SD 11.9 years; range 20-64 years), were included in the analysis, of which 5,068 (88.7%), 417 (7.3%) and 72 (1.3%) had normal, low, and high-grade cytological findings, respectively. Crude HR-HPV prevalence was 13.2% (95% CI, 12.7-13.7) among women with normal cytology and increased with cytological grade. In meta-analysis the pooled HR-HPV prevalence among those with normal cytology was 0.12 (95% CIs, 0.10-0.14; 21 studies) with the highest prevalence in younger women. HPV 16 and HPV 18 specific estimates were 0.03 (95% CI, 0.02-0.05) and 0.01 (95% CI, 0.01-0.02), respectively. The findings of this Northern Ireland study and meta-analysis verify the prevalent nature of HPV infection among younger women. Reporting of the type-specific prevalence of HPV infection is relevant for evaluating the impact of future HPV immunization initiatives, particularly against HR-HPV types other than HPV 16 and 18. J. Med. Virol. 85:295-308, 2013. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Soil conditioning of sand for EPB applications:A laboratory research

EPB tunnelling requires the application of soil conditioning to increase its field of applicability particularly for cohesionless soils. Choosing the most suitable conditioning set for the various soils requires the use of a feasible laboratory test which can permit to define the characteristics of the conditioned soils and provide measurable data. A series of tests has been carried out using a laboratory screw conveyor device which was designed for this purpose and which simulates the extraction of the spoil from a pressure chamber in a similar way as in EPB tunnelling. The tested soils were medium-grain sands with varying amounts of silt and the tested conditioned mixtures were obtained with different water contents and amounts of foam. A simple slump test was also used to analyze the global characteristics of the conditioned soils. The test has shown that the proposed laboratory procedure permits a quantitative comparison to be made between different conditioning amounts and agents on the basis of measurable parameters. © 2007 Elsevier Ltd. All rights reserved.

The effect of multiple micronutrient supplementation on left ventricular ejection fraction in patients with chronic stable heart failure: a randomized, placebo-controlled trial:A randomized, placebo-controlled trial

Objectives: This study sought to investigate the effect of a multiple micronutrient supplement on left ventricular ejection fraction (LVEF) in patients with heart failure. Background: Observational studies suggest that patients with heart failure have reduced intake and lower concentrations of a number of micronutrients. However, there have been very few intervention studies investigating the effect of micronutrient supplementation in patients with heart failure. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group study involving 74 patients with chronic stable heart failure that compared multiple micronutrient supplementation taken once daily versus placebo for 12 months. The primary endpoint was LVEF assessed by cardiovascular magnetic resonance imaging or 3-dimensional echocardiography. Secondary endpoints were Minnesota Living With Heart Failure Questionnaire score, 6-min walk test distance, blood concentrations of N-terminal prohormone of brain natriuretic peptide, C-reactive protein, tumor necrosis factor alpha, interleukin-6, interleukin-10, and urinary levels of 8-iso-prostaglandin F2 alpha. Results: Blood concentrations of a number of micronutrients increased significantly in the micronutrient supplement group, indicating excellent compliance with the intervention. There was no significant difference in mean LVEF at 12 months between treatment groups after adjusting for baseline (mean difference: 1.6%, 95% confidence interval: -2.6 to 5.8, p = 0.441). There was also no significant difference in any of the secondary endpoints at 12 months between treatment groups. Conclusions: This study provides no evidence to support the routine treatment of patients with chronic stable heart failure with a multiple micronutrient supplement. (Micronutrient Supplementation in Patients With Heart Failure [MINT-HF]; NCT01005303).

Key performance indicators – A new approach for specifying concrete and assessing state of health of concrete structure

The focus of this paper is to outline a method for consolidating and implementing the work on performance-based specification and testing. First part of the paper will review the mathematical significance of the variables used in common service life models. The aim is to identify a set of significant variables that influence the ingress of chloride ions into concrete. These variables are termed as Key Performance Indicators (KPI’s). This will also help to reduce the complexity of some of the service life models and make them more appealing for practicing engineers. The second part of the paper presents a plan for developing a database based on these KPI’s so that relationships can then be drawn between common concrete mix parameters and KPI’s. This will assist designers in specifying a concrete with adequate performance for a particular environment. This, collectively, is referred to as the KPI based approach and the concluding remarks will outline how the authors envisage the KPI theory to relate to performance assessment and monitoring.

Evaluating environmental enrichment options for commercial broiler chickens

Implications Provision of environmental enrichment in line with that required by welfare-based quality assurance schemesdoes not always appear to lead to clear improvements in broiler chicken welfare. This research perhaps serves to highlightthe deficit in information regarding the ‘real world’ implications of enrichment with perches, string and straw bales.

Introduction Earlier work showed that provision of natural light and straw bales improved leg health in commercial broilerchickens (Bailie et al., 2013). This research aimed to determine if additional welfare benefits were shown in windowedhouses by increasing straw bale provision (Study 1), or by providing perches and string in addition to straw bales (Study 2).

Material and methods Commercial windowed houses in Northern Ireland containing ~23,000 broiler chickens (placed inhouses as hatched) were used in this research which took place in 2011. In Study 1 two houses on a single farm wereassigned to one of two treatments: (1) 30 straw bales per house (1 bale/44m2), or (2) 45 straw bales per house (1bale/29m2). Bales of wheat straw, each measuring 80cm x 40cm x 40cm were provided from day 10 of the rearing cycle,as in Bailie et al. (2013). Treatments were replicated over 6 production cycles (using 276,000 Ross 308 and Cobb birds),and were swapped between houses in each replicate. In Study 2, four houses on a single farm were assigned to 1 of 4treatments in a 2 x 2 factorial design. Treatments involved 2 levels of access to perches (present (24/house), or absent), and2 levels of access to string (present (24/house), or absent), and both types of enrichment were provided from the start of thecycle. Each perch consisted of a horizontal, wooden beam (300 cm x 5 cm x 5cm) with a rounded upper edge resting on 2supports (15 cm high). In the string treatment, 6 pieces of white nylon string (60 cm x 10 mm) were tied at their mid-pointto the wire above each of 4 feeder lines. Thirty straw bales were also provided per house from day 10. This study wasreplicated over 4 production cycles using 368,000 Ross 308 birds. In both studies behaviour was observed between 0900and 1800 hours in weeks 3-5 of the cycle. In Study 1, 8 focal birds were selected in each house each week, and generalactivity, exploratory and social behaviours recorded directly for 10 minutes. In Study 2, 10 minute video recordings weremade of 6 different areas (that did not contain enrichment) of each house each week. The percentage of birds engaged inlocomotion or standing was determined through scan sampling these recordings at 120 second intervals. Four perches andfour pieces of string were filmed for 25 mins in each house that contained these enrichments on one day per week. The totalnumber of times the perch or string was used was recorded, along with the duration of each bout. In both studies, gaitscores (0 (perfect) to 5 (unable to walk)) and latency to lie (measured in seconds from when a bird had been encouraged tostand) were recorded in 25 birds in each house each week. Farm and abattoir records were also used in both studies todetermine the number of birds culled for leg and other problems, mortality levels, slaughter weights, and levels of pododermatitis and hock burn. Data were analysed using SPSS (version 20.0) and treatment and age effects on behaviouralparameters were determined in normally distributed data using ANOVA (‘Straw bale density*week’, or‘string*perches*week’ as appropriate), and in non-normally distributed data using Kuskall-Wallace tests (P<0.05 forsignificance) . Treatment (but not age) effects on performance and health data were determined using the same testsdepending on normality of data.

Results Average slaughter weight, and levels of mortality, culling, hock burn and pododermatitis were not affected bytreatment in either study (P<0.05). In Study 1 straw bale (SB) density had no significant effect on the frequency orduration of behaviours including standing, walking, ground pecking, dust bathing, pecking at bales or aggression, or onaverage gait score (P>0.05). However, the average latency to lie was greater when fewer SB were provided (30SB 23.38s,45SB 18.62s, P<0.01). In Study 2 there was an interaction between perches (Pe) and age in lying behaviour, with higherpercentages of birds observed lying in the Pe treatment during weeks 4 and 5 (week 3 +Pe 77.0 -Pe 80.9, week 4 +Pe 79.5 -Pe 75.2, week 5 +Pe 78.4 -Pe 76.2, P<0.02). There was also a significant interaction between string (S) and age inlocomotory behaviour, with higher percentages of birds observed in locomotion in the string treatment during week 3 butnot weeks 4 and 5 (week 3 +S 4.9 -S 3.9, week 4 +S 3.3 -S 3.7, week 5 +S 2.6 -S 2.8, P<0.04). There was also aninteraction between S and age in average gait scores, with lower gait scores in the string treatment in weeks 3 and 5 (week3: +S 0.7, -S 0.9, week 4: +S 1.5, -S 1.4, week 5: +S 1.9, -S 2.0, P<0.05). On average per 25 min observation there were15.1 (±13.6) bouts of perching and 19.2 (±14.08) bouts of string pecking, lasting 117.4 (±92.7) and 4.2 (±2.0) s for perchesand string, respectively.

Conclusion Increasing straw bale levels from 1 bale/44m2 to 1 bale/29m2 floor space does not appear to lead to significantimprovements in the welfare of broilers in windowed houses. The frequent use of perches and string suggests that thesestimuli have the potential to improve welfare. Provision of string also appeared to positively influence walking ability.However, this effect was numerically small, was only shown in certain weeks and was not reflected in the latency to lie.Further research on optimum design and level of provision of enrichment items for broiler chickens is warranted. Thisshould include measures of overall levels of activity (both in the vicinity of, and away from, enrichment items).