Corneal Endothelium Viability Assay Using Trypan Blue Dye After Preloaded Descemet Membrane Endothelial Keratoplasty Graft Preparation.

PURPOSE: The purpose of this study was to establish a validated method, consistent with Eye Bank Association of America medical standards, for evaluating endothelial cell loss (ECL) from an entire Descemet membrane endothelial keratoplasty (DMEK) graft using trypan blue dye as an alternative to specular microscopy. METHOD: Twenty-nine corneas were prepared for preloaded DMEK by a single technician, and the endothelium was stained with trypan blue dye for 30 seconds. The technician estimated total cell loss as a percentage of the graft and captured an image. Images were evaluated by a blinded technician using ImageJ software to determine ECL and compared with endothelial cell density from specular microscopy. Tissue processing intervals were analyzed for 4 months before and after implementation of this method. RESULTS: For the 29 grafts, there was no statistically significant difference ( t test, P = 0.285) between ECL estimated by a processor (mean = 5.8%) and ECL calculated using an ImageJ software (mean = 5.1%). The processor tended to estimate greater ECL than the actual ECL determined by ImageJ (paired t test, P = 0.022). Comparatively, postprocessing endothelial cell density measured by specular microscopy were higher compared with the preprocessing endothelial cell density (mean = 4.5% P = 0.0006). After implementation of this evaluation method, DMEK graft processing time intervals were reduced by 47.9% compared with specular microscopy evaluation ( P < 0.001). CONCLUSIONS: Our results show that visual ECL estimation using trypan blue staining by a DMEK graft processor is a reliable and efficient method for endothelial assessment. Unlike specular microscopy, this method achieves comprehensive visualization of the entire endothelium, reduces total time out of cold storage, and decreases total time required to prepare and evaluate DMEK grafts.

Safety of Long-Term Storage and Shipping of Prestripped, Prestained, and Preloaded Descemet Membrane Endothelial Keratoplasty Tissue.

PURPOSE: The purpose of this study was to determine the safety of long-term storage and shipping of prestripped, prestained, and preloaded Descemet membrane endothelial keratoplasty (pDMEK) grafts. METHODS: A total of 33 cadaveric corneas were prestripped, prestained, and preloaded using modified Jones tube injectors as pDMEK. The corneas were masked to groups that were prepared <9 hours (control), 48 hours, and 72 hours before unloading and analysis. The 48- and 72-hour tissues were shipped by airfreight on each day before arrival to simulate domestic and international shipping. The corneas were then stained using Calcein AM vital dye (Molecular Probes, Eugene, OR) and imaged using an inverted confocal microscope. Primary outcome measures were endothelial cell loss (ECL, %) and sustainability of staining. MetaMorph software (Molecular Devices, Downingtown, PA) was used to quantify ECL, and staining was evaluated subjectively using all-or-none rating. RESULTS: There was no difference in the mean ECL for the control, 48-hour, and 72-hour groups, which were 25.1% ± 8.8%, 26.4% ± 17.5%, and 19.2% ± 11.5%, respectively (P = 0.45; Kruskal-Wallis test). In all tissues of each group, no loss of staining was identified at each time point of analysis. CONCLUSIONS: ECL in pDMEK tissue prepared 48 and 72 hours in advance and shipped using standard methods is similar to that in pDMEK tissue prepared on the same day. These findings support the safety of domestic and international shipping of pDMEK grafts.

Imaging of Corneal Neovascularization: Optical Coherence Tomography Angiography and Fluorescence Angiography.

Purpose: The purpose of this study was to compare optical coherence tomography angiography (OCTA) and indocyanine green angiography (ICGA) for the assessment of corneal neovascularization (CoNV). Methods: Patients with CoNV extending at least 3 mm into the cornea were included. All patients underwent corneal imaging at the same visit. Images were recorded using the AngioVue OCTA system (Optovue, Inc.) with the long corneal adaptor module (CAM-L). ICGA images were recorded with fluorescent filters using the Heidelberg system (HRA2 Scanning Laser Ophthalmoscope; Heidelberg Engineering). Images were graded for quality by two independent observers. Vessel parameters: area, number, diameter, branch and end points, and tortuosity, were compared between devices. Bland-Altman plots were used to assess differences between parameters. Results: Fifteen patients with CoNV predominantly associated with microbial keratitis were included. Mean subjective image quality score was better for ICGA (3.3 ± 0.9) than for OCTA (2.1 ± 1.2, P = 0.002), with almost perfect interobserver agreement for ICGA images (κ = 0.83) and substantial agreement for OCTA images (κ = 0.69). Agreement of grading of all investigated vessel parameters between ICGA and OCT images was slight to moderate, with significant differences found for vessel diameter (-8.98 µm, P = 0.01, 95% limits of agreement [LOA]: -15.89 to -2.07), number of branch (25.93, P = 0.09, 95% LOA: -4.31 to 56.17), and terminal points (49, P = 0.05, 95% LOA: 0.78 to 97.22). Conclusion: Compared with ICGA, current OCTA systems are less precise in capturing small vessels in CoNV complexes, and validation studies are needed for OCTA segmentation software. OCTA, however, complements ICGA by providing evidence of red blood cell flow, which together with depth information, may be helpful when planning treatment of CoNV.

How true outcomes-based commissioning can really 'liberate' healthcare services.

Healthcare systems all over the world face the challenge of variable care quality, inefficiency and increasing costs. A potential solution is value-based healthcare, where the aim is to achieve the best outcomes at the lowest cost. However, the measurement of outcomes that really reflect what matters most to patients is currently rudimentary. The International Consortium for Health Outcomes Measurement (ICHOM) has been developed to create globally consistent sets of outcomes that reflect what matters most to patients. Incorporating such sets of outcomes into capitated outcome-based and incentivised contracts will incentivise better outcomes and greater cost efficiency.

The HTA core model: a novel method for producing and reporting health technology assessments.

OBJECTIVES: The aim of this study was to develop and test a generic framework to enable international collaboration for producing and sharing results of health technology assessments (HTAs). METHODS: Ten international teams constructed the HTA Core Model, dividing information contained in a comprehensive HTA into standardized pieces, the assessment elements. Each element contains a generic issue that is translated into practical research questions while performing an assessment. Elements were described in detail in element cards. Two pilot assessments, designated as Core HTAs were also produced. The Model and Core HTAs were both validated. Guidance on the use of the HTA Core Model was compiled into a Handbook. RESULTS: The HTA Core Model considers health technologies through nine domains. Two applications of the Model were developed, one for medical and surgical interventions and another for diagnostic technologies. Two Core HTAs were produced in parallel with developing the model, providing the first real-life testing of the Model and input for further development. The results of formal validation and public feedback were primarily positive. Development needs were also identified and considered. An online Handbook is available. CONCLUSIONS: The HTA Core Model is a novel approach to HTA. It enables effective international production and sharing of HTA results in a structured format. The face validity of the Model was confirmed during the project, but further testing and refining are needed to ensure optimal usefulness and user-friendliness. Core HTAs are intended to serve as a basis for local HTA reports. Core HTAs do not contain recommendations on technology use.

The adaptation of health technology assessment reports: identification of the need for, and development of, a toolkit to aid the process.

OBJECTIVES: Europe has many health technology assessment (HTA) agencies, each producing their own HTA reports. Adapting HTA reports for different contexts could reduce the need for multiple reports on the same health technology with resultant saving of time and resources. This study aims to examine and understand the process of adaptation, and to develop a toolkit that would help the adaptation of reports produced by other countries. METHODS: The methods used were a review of the literature; a survey of twenty-nine European HTA organizations, two rounds of a Delphi survey, a face-to-face meeting of twenty-one European network for Health Technology Assessment (EUnetHTA) representatives, iterative rounds of review, and two rounds of quality assurance testing (termed applicability testing). RESULTS: Descriptions of previous examples of adaptation in the literature are sparse. Most respondents had previous experience in adapting reports, and all believed that adaptation was useful, and there was the ability to benefit from the use of a toolkit to aid in the process. EUnetHTA Partners developed and tested an adaptation toolkit. The toolkit is composed of a series of checklists and resources that identify or clarify the relevance, reliability, and transferability of data and information from existing reports. CONCLUSIONS: Consensus of opinion from twenty-nine European organizations/networks has indicated that the adaptation of HTA reports would be desirable and beneficial. A toolkit was developed to help with the adaptation of HTA reports produced in other settings. This collection of resources is available for use by all HTA agencies and can be accessed at: http://www.eunethta.net/upload/WP5/EUnetHTA_HTA_Adaptation_Toolkit_October08.pdf.

The health technology assessment adaptation toolkit: description and use.

OBJECTIVES: Adapting health technology assessment (HTA) reports for different contexts could reduce the need for multiple reports on the same health technology with resultant saving of time and resources. This article describes an instrument, the adaptation toolkit, which has been developed to aid in the process of adaptation of HTA reports. METHODS: The toolkit was developed by a partnership of HTA agencies and networks from across Europe. The role of the toolkit is to guide the user through the process of selecting possible relevant material from these report(s), assessing the relevance, reliability, and transferability of the material, and adapting it for the desired context. RESULTS: The adaptation toolkit has been developed, it comprises a collection of resources that help the user assess whether data and information in existing HTA reports should and could be adapted for their own setting. The toolkit contains two sections: a preliminary speedy sifting section and the main toolkit. The main toolkit includes five domains: (i) technology use and development, (ii) safety, (iii) effectiveness (including efficacy), (iv) economic evaluation, and (v) organizational aspects. Legal, ethical, and social aspects are beyond the scope of the toolkit. The toolkit is designed for the adaptation of evidence synthesis rather than primary research. CONCLUSIONS: The completed current version of the toolkit contains checklists and resources to aid in the adaptation of HTA reports. This collection of resources is available for use by all HTA agencies and can be accessed at: http://www.eunethta.net/upload/WP5/EUnetHTA_HTA_Adaptation_Toolkit_October08.pdf..

Enhancing understanding: the development of a glossary of health technology assessment adaptation terms.

BACKGROUND: The way people use health technology assessment (HTA) terms varies considerably across Europe. Such variation can lead to misunderstandings when reading HTA reports from different contexts. This work is one of the outputs of the EUnetHTA Project and was undertaken between 2006 and 2008. OBJECTIVES: The aim of this study was to develop a glossary of HTA adaptation terms to help reduce the misunderstandings of terms used in HTA reports from contexts other than the reader's own. METHODS: Several HTA glossaries were examined to identify ways in which an additional glossary could offer readers something new and to identify adaptation terms for inclusion. Twenty-eight European HTA organizations provided terms for the glossary and drafted descriptions and examples of how each specific term was used in their particular setting. The organizations then commented on the descriptions provided by the other groups and worked together to draft a single description for certain terms. RESULTS: A glossary of HTA adaptation terms was developed. It provides a comprehensive range of descriptions, examples, and comments for forty-two potentially confusing HTA terms related to adaptation. CONCLUSIONS: This glossary will be a valuable resource for European HTA agencies when reading HTA reports produced in different contexts and for adapting HTA reports produced in other countries. The glossary will help improve understanding and help facilitate the adaptation process.

Guideline-based early rehabilitation after myocardial infarction. A pragmatic randomised controlled trial.

OBJECTIVES: To determine the effectiveness of individualised educational behavioural treatment delivered by cardiac nurses in hospital compared to usual care for patients following acute myocardial infarction. METHODS: One hundred and fourteen consecutive patients were randomised to receive the intervention or usual care. Outcome assessment was by self-report questionnaire (the Hospital Anxiety and Depression Scale and Dartmouth COOP Health Status), interview at 1 month, and self-report at 3 and 12 months. The primary outcome was improvement in the Dartmouth COOP total score from baseline to 3 months. RESULTS: Four patients needed to be treated to give an additional patient with improvement in health status at 3 months (number needed to treat [NNT] 4, 95% confidence intervals [CIs] 3 to 12). The intervention group were more confident about returning to activities 1 month after discharge from hospital. Treated patients had fewer further treatment needs. CONCLUSIONS: An individualised educational behavioural treatment delivered by cardiac nurses in hospital may have substantial benefits. A large-scale pragmatic RCT is needed.