Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.

Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.

Improving diabetes care for people with intellectual disabilities: a qualitative study exploring the perceptions and experiences of professionals in diabetes and intellectual disability services.

BACKGROUND: Globally, diabetes is increasing with concerns about the impact on outcomes, including premature death and the costs associated with managing the condition. Research indicates that adults with intellectual disabilities (ID) are two to three times more likely to develop diabetes; however, there has been limited focus on diabetes service utilisation in this population. The aim of this study is to explore the perceptions and experiences of diabetes and ID practitioners. METHODS: A series of 1:1 semi-structured interviews were undertaken in one Scottish health service area. In total, 29 qualitative interviews were conducted: 10 with diabetes practitioners from primary and secondary care, 14 from ID services and 5 from community care services regarding diabetes service provision for this population. Thematic content analysis was undertaken to identify the themes and subthemes. RESULTS: Three main themes were identified: (1) enabling access to services to meet diabetes-related care needs of people with ID; (2) communication and service improvements between staff, patients and across services; and (3) providing person-centred diabetes care and developing adapted resources to increase patient self-care. CONCLUSIONS: The findings of this study have important international implications in how diabetes practitioners plan and deliver services for people with ID and other vulnerable groups with limited cognitive ability and communication skills and difficulties in self-management. The findings highlight that access to diabetes education and adapted resources is needed, and if 'reasonable adjustments' are made to service provision and practice, people with ID can benefit from improved healthcare. Developing joint clinics to share knowledge and resources between diabetes and ID practitioners may improve service delivery and continuity of care, and thereby diminish the costs of not providing quality care.

Polarisation of equine pregnancy outcome associated with a maternal MHC class I allele: Preliminary evidence.

Identification of risk factors which are associated with severe clinical signs can assist in the management of disease outbreaks and indicate future research areas. Pregnancy loss during late gestation in the mare compromises welfare, reduces fecundity and has financial implications for horse owners. This retrospective study focussed on the identification of risk factors associated with pregnancy loss among 46 Thoroughbred mares on a single British stud farm, with some but not all losses involving equid herpesvirus-1 (EHV-1) infection. In a sub-group of 30 mares, association between pregnancy loss and the presence of five common Thoroughbred horse haplotypes of the equine Major Histocompatibility Complex (MHC) was assessed. This involved development of sequence specific, reverse transcriptase polymerase chain reactions and in several mares, measurement of cytotoxic T lymphocyte activity. Of the 46 mares, 10 suffered late gestation pregnancy loss or neonatal foal death, five of which were EHV-1 positive. Maternal factors including age, parity, number of EHV-1 specific vaccinations and the number of days between final vaccination and foaling or abortion were not significantly associated with pregnancy loss. In contrast, a statistically significant association between the presence of the MHC class I B2 allele and pregnancy loss was identified, regardless of the fetus/foal's EHV-1 status (p=0.002). In conclusion, this study demonstrated a significantly positive association between pregnancy loss in Thoroughbred mares and a specific MHC class I allele in the mother. This association requires independent validation and further investigation of the mechanism by which the mare's genetic background contributes to pregnancy outcome.

New assays to measure equine influenza virus-specific Type 1 immunity in horses.

Equine influenza virus (EIV) is a leading cause of respiratory disease in horses. Equine influenza infection induces a long-term immunity to re-infection. Recent strategies of vaccination aim to mimic this immunity by stimulating both antibody and cellular immune responses. Cell-mediated immunity (CMI) to influenza is well defined in man, but little has been done to characterise the responses in the horse. Additionally, the development of reliable assays for the measurement of equine CMI has lagged behind serological methods and vaccine development. In this study, two methods of measuring EIV-specific T lymphocyte responses have been developed. An EIV 'bulk' cytotoxic T lymphocytes (CTL) assay using equine dermal fibroblasts as target cells has been adapted from a method used in the 1980s. This method was also complemented with a new EIV-specific IFNgamma synthesis assay. When compared with the measurement of EIV-specific IFNgamma synthesis previously described, this method required the amplification of EIV-specific lymphocytes by culture and was sensitive enough to detect stimulation of EIV-specific T lymphocytes induced by experimental infection with EIV or vaccination with recombinant canarypox viruses coding for EIV-HA molecules. This study provides the tools to characterise the stimulation of CMI by the new generation of vaccines against equine influenza.

Project examining effectiveness in clinical ethics (PEECE): phase 1-- descriptive analysis of nine clinical ethics services.

OBJECTIVE: The field of clinical ethics is relatively new and expanding. Best practices in clinical ethics against which one can benchmark performance have not been clearly articulated. The first step in developing benchmarks of clinical ethics services is to identify and understand current practices. DESIGN AND SETTING: Using a retrospective case study approach, the structure, activities, and resources of nine clinical ethics services in a large metropolitan centre are described, compared, and contrasted. RESULTS: The data yielded a unique and detailed account of the nature and scope of clinical ethics services across a spectrum of facilities. General themes emerged in four areas-variability, visibility, accountability, and complexity. There was a high degree of variability in the structures, activities, and resources across the clinical ethics services. Increasing visibility was identified as a significant challenge within organisations and externally. Although each service had a formal system for maintaining accountability and measuring performance, differences in the type, frequency, and content of reporting impacted service delivery. One of the most salient findings was the complexity inherent in the provision of clinical ethics services, which requires of clinical ethicists a broad and varied skill set and knowledge base. Benchmarks including the average number of consults/ethicist per year and the hospital beds/ethicist ratio are presented. CONCLUSION: The findings will be of interest to clinical ethicists locally, nationally, and internationally as they provide a preliminary framework from which further benchmarking measures and best practices in clinical ethics can be identified, developed, and evaluated.

Clinical bioethics integration, sustainability, and accountability: the Hub and Spokes Strategy.

The "lone" clinical bioethicist working in a large, multisite hospital faces considerable challenges. While attempting to build ethics capacity and sustain a demanding range of responsibilities, he or she must also achieve an acceptable level of integration, sustainability, and accountability within a complex organisational structure. In an effort to address such inherent demands and to create a platform towards better evaluation and effectiveness, the Clinical Ethics Group at the Joint Centre for Bioethics at the University of Toronto is implementing the Hub and Spokes Strategy at seven hospitals. The goal of the Hub and Spokes Strategy is to foster an ethical climate and strengthen ethics capacity broadly throughout healthcare settings as well as create models in clinical bioethics that are excellent and effective.

Workers' understanding of chemical risks: electroplating case study.

BACKGROUND: There is limited research concerning how small companies in particular, respond to health and safety messages. AIMS: To understand individuals' knowledge and beliefs about chemical risks and to compare these with those of experts. METHODS: The use of chromic acid in particular, and also other chemicals associated with chrome plating were studied. All chromium plating firms were based in the West Midlands. The methodology involved initial face to face interviews (n = 21) with chromium platers, structured questionnaires (n = 84) to test the prevalence of beliefs identified in the interviews, an expert questionnaire, and a workshop to discuss findings. The responses of platers were compared with those of occupational health and safety experts. RESULTS: Although chromium platers appeared to understand the short term adverse effects of the chemicals to which they are exposed, their understanding of long term, or chronic effects appeared to be incomplete. They had good knowledge of acute effects based primarily on experience. Platers were aware of the hazardous nature of the chemicals with which they work, but did not draw distinction between the terms "hazards" and "risks". They had difficulties articulating the effects of the chemicals and how exposure might occur; although it is inappropriate to equate this with lack of knowledge. A significant minority of platers displayed deficiencies in understanding key technical terms used in Safety Data Sheets. CONCLUSIONS: This study provides a method which can be used to gain some understanding of workers' knowledge and beliefs about risks that they are exposed to in the workplace. The study also identifies gaps between the platers' knowledge and beliefs and those of experts. New risk information needs to be designed which addresses the information needs of platers using language that they understand.

Bitoric laser in situ keratomileusis for the correction of simple myopic and mixed astigmatism.

OBJECTIVE: To evaluate the safety and efficacy of bitoric laser in situ keratomileusis (LASIK) for the correction of simple myopic and mixed astigmatism. DESIGN: Retrospective, single-center, and noncomparative case series. PARTICIPANTS: Eighty-six eyes of 56 patients were analyzed for this study. Six-month and 1-year follow-up data were available on 86 eyes and 72 eyes, respectively. Eyes were divided in two groups according to the type of astigmatism: myopic astigmatism with low sphere (< -2 diopters) and mixed astigmatism. The range of astigmatism was 1.25 to 7.5 diopters. INTERVENTION: LASIK was performed using the Automated Corneal Shaper (ACS) microkeratome (Bausch & Lomb, Claremont, CA) to create a cornea flap using the 130- or 160-micron thickness plate. A bitoric mid-stromal ablation was performed using the Nidek EC-5000 excimer laser (Nidek Company, Gamagori, Japan). MAIN OUTCOME MEASURES: Uncorrected visual acuity, manifest refraction, and best spectacle-corrected visual acuity were the parameters measured preoperatively and at months 1, 3, 6, and 12. RESULTS: At the last visit, an uncorrected visual acuity of 20/20 or better was achieved in 77% and 68% of the myopic and mixed astigmatism groups, respectively. Ninety-two percent of all eyes had a mean spherical equivalent within +/- 0.50 diopter of emmetropia. A mean decrease in the vectorial magnitude of the astigmatism of 94% and 91% was achieved for those eyes with myopic and mixed astigmatism, respectively. There was no loss of best spectacle-corrected visual acuity. In two eyes, the axis of the positive cylinder was misaligned. CONCLUSION: Bitoric LASIK is an effective procedure to correct myopic and mixed astigmatism. Eighty-five percent of the eyes achieved an uncorrected visual acuity of 20/25 or better and had a final cylinder of 0.5 diopter or less. It is a safe operation, because no eyes lost any lines of best spectacle-corrected visual acuity. Longer follow-up may be needed to assess these results.

Slit skiascopic-guided ablation using the Nidek laser.

PURPOSE: To present the approach of using a scanning slit refractometer (the ARK 10000) in conjunction with a corneal topography system to guide customized corneal ablation. This diagnostic system is coupled with the Nidek EC-5000 system which combines scanning slit and a scanning small area ablation (1.0 mm) to perform a customized ablation. METHODS: The ARK 10000 diagnostic system which contains a scanning slit refractometer is described. Information generated from the ARK 10000 wavefront sensor and corneal topography system can be coupled to the new Nidek EC-5000 excimer laser system, which combines the larger area of scanning slit ablation with the small area (1.0 mm) ablation. RESULTS: The Nidek ARK 10000 diagnostic system captures wavefront information using a retinoscopic system which is converted into a refractive power map. This is different from other autorefraction systems in that it has four sensors at different diameters of the cornea and captures 1440 points in 0.4 seconds. This map is used in conjunction with corneal topography-captured simultaneously. This information is then combined to perform a customized ablation using the new Nidek EC-5000 system. CONCLUSIONS: The ARK 10000 diagnostic system represents a different approach to customized ablation in that it combines a corneal topography system with a wavefront system and a larger treatment area of the traditional scanning slit ablation with a new small area ablation treatment for greater efficiency.

Photoastigmatic refractive keratectomy in myopes. Nidek US Investigators Group.

PURPOSE: Photoastigmatic refractive keratectomy (PARK) was studied in a multi-center clinical trial. The Nidek EC-5000 excimer laser was evaluated for its effect on refraction, visual acuity, and safety measures as part of a U.S. Food and Drug Administration (FDA) regulated study. METHODS: Eight U.S. centers enrolled adults with eyes having refractive astigmatism up to 4.00 D and a myopic spherical equivalent refraction up to -8.00 D. Results are reported for 749 eyes of 486 patients with at least 6 months follow-up. The rectangular beam scanning Nidek EC-5000 used a 5.5-mm-diameter treatment zone, a 7.0-mm-diameter peripheral blend zone, and a 40 Hz pulse rate for surface treatment of myopic astigmatism. Nomogram corrections to machine settings were required to achieve the desired results. RESULTS: Preoperative average spherical equivalent refraction of -4.90+/-1.74 D was reduced to -0.02+/-0.79 D at 6 months. Refractive stability was established at 3 months. Over 62% of eyes were within +/-0.50 D of desired correction at 6 months, with over 86% within +/-1.00 D. Uncorrected visual acuity improved by an average of 10 Snellen lines; over 64% of eyes saw 20/20 or better uncorrected and over 93% saw 20/40 or better uncorrected at 6 and 12 months. PARK treatment effectively reduced astigmatism with little average axis error or magnitude error. Corneal haze and safety concerns were minimal. CONCLUSIONS: Photoastigmatic refractive keratectomy using the Nidek EC-5000 excimer laser provided significant reduction of myopia and astigmatism, with minimal complications.

Customized corneal ablation and super vision.

PURPOSE: To review the early development of new technologies that are becoming available through customized corneal ablation techniques. METHODS: The authors describe the early development of two diagnostic methods to perform customized corneal ablation as well as a variety of new treatment modalities in development. RESULTS AND CONCLUSION: Results using the wavefront sensors indicate that these techniques have the potential to be more sensitive than traditional refraction and keratometry. Subtle defects such as coma and spherical aberration can be detected and treated. A whole series of new technologies are being incorporated to treat patients with customized corneal ablation. [J Refract Surg 2000;16(suppl):S230-S235].

Sterile interface keratitis after laser in situ keratomileusis: three episodes in one patient with concomitant contact dermatitis of the eyelids.

PURPOSE: To illustrate a case in which sterile interface keratitis after laser in situ keratomileusis (LASIK) occurred concomitantly with an allergic contact dermatitis of the eyelids. METHODS: Retrospective case review. RESULTS: Resolution of the interface keratitis and dermatitis occurred following an intense course of topical corticosteroids and brief course of oral corticosteroids. Despite an attempt to eliminate potential causes, the same patient developed interface keratitis in the fellow eye following both the initial LASIK and an enhancement, in which no microkeratome was used. Intense treatment with both topical and oral corticosteroids led to a final uncorrected visual acuity of 20/20 in the right eye and 20/25+2 in the left eye. CONCLUSION: The etiology and mechanism of sterile interface keratitis after LASIK are unknown, but are probably multifactorial. The concomitant contact dermatitis reaction may indicate a common immune mechanism.

Sterile interface keratitis associated with micropannus hemorrhage after laser in situ keratomileusis.

Numerous etiologies have been suspected to lead to sterile interface keratitis after laser in situ keratomileusis. This tan interface haze with a rippled appearance has been called Sands of the Sahara. We present 2 cases in which red blood cells entered the interface after a small hemorrhage from peripheral corneal vascularization during the microkeratome pass. Although this bleeding was controlled and all visible blood cells were removed at surgery, both patients developed the appearance of a focal interface keratitis on the first postoperative day.

Excimer ablation design and elliptical transition zones.

PURPOSE: To describe the rationale behind elliptical and other transition designs used with the excimer laser. SETTING: Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon, USA. METHODS: Ablation zone designs were analyzed for the number of transition points for myopia and hyperopia. The advantages and disadvantages of elliptical transition zones are demonstrated graphically, with an emphasis on smooth ablation zone design to maximize the optics and biologic tolerance by the eye. RESULTS: The use of an individualized elliptical transition maximizes a circular effective optical zone and can enhance the smoothness of the transition zone while minimizing excessive tissue removal. CONCLUSION: Elliptical transition zones may improve the optics and biologic tolerance of excimer laser treatments.

The built environment as a component of quality care: understanding and including the patient's perspective.

BACKGROUND: Although there has been little systematic assessment of how the built environment of health care facilities affects the quality of care, the built environment is a major element of structure of care--one of three facets of quality. Yet in contrast to the growing trend of using consumer perceptions of both processes and outcomes of care in QI activities, quality assessments of the structure of care do not currently rely on patient feedback. PURPOSE OF PROJECT: During the initial phase of a multiphase project, nine focus groups were conducted in 1997 to identify the salient dimensions of experience from the patient's perspective. The content of these focus groups guided the development of assessment tools in the second phase of the project, which began in February 1998. FINDINGS: Participants in three focus groups that were held in each of three settings--ambulatory care, acute care, and long term care--described in detail a variety of reactions to the built environment. Analysis revealed eight consistent themes in what patients and family member consumers look for in the built environment of health care. In all three settings, they want an environment, for example, that facilitates a connection to staff and caregivers, is conducive to a sense of well-being, and facilitates a connection to the outside world. DISCUSSION: Data derived from the focus group research has guided the development of quantitative survey and assessment tools. For each setting, patient-centered checklists and questionnaires are designed to help institutions set priorities for the improvement of facility design from the patient's perspective.