Which value aspects are relevant for the evaluation of medical devices? Exploring stakeholders' views through a Web-Delphi process.

BACKGROUND: Implementation and uptake of health technology assessment for evaluating medical devices require including aspects that different stakeholders consider relevant, beyond cost and effectiveness. However, the involvement of stakeholders in sharing their views still needs to be improved. OBJECTIVE: This article explores the relevance of distinct value aspects for evaluating different types of medical devices according to stakeholders' views. METHODS: Thirty-four value aspects collected through literature review and expert validation were the input for a 2-round Web-Delphi process. In the Web-Delphi, a panel of participants from five stakeholders' groups (healthcare professionals, buyers and policymakers, academics, industry, and patients and citizens) judged the relevance of each aspect, by assigning a relevance-level ('Critical', 'Fundamental', 'Complementary', or 'Irrelevant'), for two types of medical devices separately: 'Implantable' and 'In vitro tests based on biomarkers'. Opinions were analysed at the panel and group level, and similarities across devices were identified. RESULTS: One hundred thirty-four participants completed the process. No aspects were considered 'Irrelevant', neither for the panel nor for stakeholder groups, in both types of devices. The panel considered effectiveness and safety-related aspects 'Critical' (e.g., 'Adverse events for the patient'), and costs-related aspects 'Fundamental' (e.g., 'Cost of the medical device'). Several additional aspects not included in existing frameworks' literature, e.g., related to environmental impact and devices' usage by the healthcare professional, were deemed as relevant by the panel. A moderate to substantial agreement across and within groups was observed. CONCLUSION: Different stakeholders agree on the relevance of including multiple aspects in medical devices' evaluation. This study produces key information to inform the development of frameworks for valuing medical devices, and to guide evidence collection.

Advancing hospital-based health technology assessment: evaluating genomic panel contracting strategies for blood tumors through a multimethodology.

INTRODUCTION: The adoption of genomic technologies in the context of hospital-based health technology assessment presents multiple practical and organizational challenges. OBJECTIVE: This study aimed to assist the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPO Lisboa) decision makers in analyzing which acute myeloid leukemia (AML) genomic panel contracting strategies had the highest value-for-money. METHODS: A tailored, three-step approach was developed, which included: mapping clinical pathways of AML patients, building a multicriteria value model using the MACBETH approach to evaluate each genomic testing contracting strategy, and estimating the cost of each strategy through Monte Carlo simulation modeling. The value-for-money of three contracting strategies - "Standard of care (S1)," "FoundationOne Heme test (S2)," and "New diagnostic test infrastructure (S3)" - was then analyzed through strategy landscape and value-for-money graphs. RESULTS: Implementing a larger gene panel (S2) and investing in a new diagnostic test infrastructure (S3) were shown to generate extra value, but also to entail extra costs in comparison with the standard of care, with the extra value being explained by making available additional genetic information that enables more personalized treatment and patient monitoring (S2 and S3), access to a broader range of clinical trials (S2), and more complete databases to potentiate research (S3). CONCLUSION: The proposed multimethodology provided IPO Lisboa decision makers with comprehensive and insightful information regarding each strategy's value-for-money, enabling an informed discussion on whether to move from the current Strategy S1 to other competing strategies.

Scenarios for population health inequalities in 2030 in Europe: the EURO-HEALTHY project experience.

BACKGROUND: Health inequalities have been consistently reported across and within European countries and continue to pose major challenges to policy-making. The development of scenarios regarding what could affect population health (PH) inequalities across Europe in the future is considered critical. Scenarios can help policy-makers prepare and better cope with fast evolving challenges. OBJECTIVE: This paper describes the three 2030 time-horizon scenarios developed under the EURO-HEALTHY project, depicting the key factors that may affect the evolution of PH inequalities across European regions. METHODS: A three-stage socio-technical approach was applied: i) identification of drivers (key factors expected to affect the evolution of PH inequalities across European regions until 2030) - this stage engaged in a Web-Delphi process a multidisciplinary panel of 51 experts and other stakeholders representing the different perspectives regarding PH inequalities; ii) generation of scenario structures - different drivers' configurations (i.e. their hypotheses for evolution) were organized into coherent scenario structures using the Extreme-World Method; and iii) validation of scenario structures and generation of scenario narratives. Stages ii) and iii) were conducted in two workshops with a strategic group of 13 experts with a wide view about PH inequalities. The scenario narratives were elaborated with the participants' insights from both the Web-Delphi process and the two workshops, together with the use of evidence (both current and future-oriented) on the different areas within the PH domain. RESULTS: Three scenarios were developed for the evolution of PH inequalities in Europe until 2030: 'Failing Europe' (worst-case but plausible picture of the future), 'Sustainable Prosperity' (best-case but plausible picture of the future), and an interim scenario 'Being Stuck' depicting a 'to the best of our knowledge' evolution. These scenarios show the extent to which a combination of Political, Economic, Social, Technological, Legal and Environmental drivers shape future health inequalities, providing information for European policy-makers to reflect upon whether and how to design robust policy solutions to tackle PH inequalities. CONCLUSIONS: The EURO-HEALTHY scenarios were designed to inform both policy design and appraisal. They broaden the scope, create awareness and generate insights regarding the evolution of PH inequalities across European regions.

Characterization of novel O-glycans isolated from tear and saliva of ocular rosacea patients.

O-Glycans in saliva and tear isolated from patients suffering from ocular rosacea, a form of inflammatory ocular surface disease, were profiled, and their structures were elucidated using high resolution mass spectrometry. We have previously shown that certain structures, particularly sulfated oligosaccharides, increased in the tear and saliva of rosacea patients. In this study, the structures of these glycans were elucidated using primarily tandem mass spectrometry. There were important similarities in the glycan profiles of tears and saliva with the majority of the structures in common. The structures of the most abundant species common to both tear and saliva, which were also the most abundant species in both, were elucidated. For sulfated species, the positions of the sulfate groups were localized. The majority of the structures were new, with the sulfated glycans comprising mucin core 1- and core 2-type structures. As both saliva and tear are rich in mucins, it is suggested that the O-glycans are mainly components of mucins. The study further illustrates the strong correspondence between the glycans in the tear and saliva of ocular rosacea patients.

The natural impact of banana inflorescences (Musa acuminata) on human nutrition.

Banana inflorescences are popularly known as 'navels,' and they are used in Brazil as nutritional complements. However, the nutritional value of banana inflorescences (male flowers and bracts) has never been studied. Therefore, plant material of Musa acuminata, cultivar "ouro", was collected in Rio de Janeiro state, Brazil, and then submitted to chemical procedures to determine its nutritional composition. The experiment was arranged a completely randomized design and performed in triplicate. The sample composition analysis showed percentual average value for moisture, protein, fat and ash as 8.21, 14.50, 4.04 and 14.43, respectively. The dehydrated inflorescences were found to contain a significant nutritive complement based on their high content of potassium (5008.26 mg / 100 g) and fiber 49.83% (lignin, cellulose and hemicelluloses) revealing important functional and nutritional properties. In a parallel evaluation, the anatomical study revealed key elements for the recognition of Musa acuminata when reduced to fragments.

Mentoring in radiology: An asset worth exploring!

Residents experience high pressure to be successful in both their career and in keeping up an optimal work-life balance. With a mentoring program, faculties can alleviate stress and provide help for their residents. It is now well established that mentor-mentee relationships during medical school, have influence in career decisions and professional identity formation. The same can be said for mentor-mentee relationships during radiology residency. In general, universal rules of mentoring are also useful and applicable in the field of radiology. These universal rules for establishing a successful mentoring relationship include creating a relationship of trust and confidentiality, clearly defining roles and responsibilities, establishing short- and long-term goals, using open and supportive communication, and collaboratively solving problems. The institutions and the radiology departments should be well prepared and aware of the responsibility to have trainees, providing time for mentors to dedicate to their academic duties. They have to implement strategies to effective mentor matching and orientation as well as the ability to provide evaluation with qualitative feedback. Periodic assessment should be warranted together with the incorporation of new technology as it plays a critical role in the training of millennial radiologists as they take the profession into a technology-laden future of medical imaging.

ANIPHI: An innovative pedagogical platform based on the Delphi method to support animal welfare teaching.

As a teaching subject, animal welfare is challenging for educators and learners, as was recently shown in a recent survey on the evolution of animal welfare teaching in Europe. Among several suggestions to overcome the current resistance to implementing animal welfare education, we highlight two. The first is that animal welfare education should be based on learner-centred approaches; the second is that it should encompass both animal welfare science and ethics and law. To the best of our knowledge, there are no learner-centred pedagogical approaches that can simultaneously explore scientific and ethical concepts. Furthermore, when exploring ethical concepts within the educational context, there is the additional challenge of being able to depart from discussion and debate to a systematic organization of knowledge. Our work simultaneously addresses these two challenges, presenting the design and implementation of a novel web-based learner-centred pedagogical platform for farm animal welfare teaching. The platform, named ANIPHI, uses the Delphi method's iterative nature as a learning process to generate both reflection and (online) debate among learners. ANIPHI can be used by educators in an online environment, in a classroom environment, or in a combination of the two environments. ANIPHI was developed within the ERASMUS+ ANICARE project and is an open web-based platform for all educators interested in teaching farm animal welfare. Given ANIPHI's flexible and user-friendly nature, the platform simultaneously exposes learners to ethical and scientific concepts in different educational realities, according to the educator's objectives. Furthermore, videos depicting different husbandry practices across different types of animal production and countries are embedded in the platform. These videos are commented on by the farmer himself and by animal scientists, which enriches the learner's experience. Educators across the ANICARE consortium have already successfully tested the ANIPHI platform for different farm animal welfare topics. We conclude this article by presenting one example of using ANIPHI in a real-life educational context, where we discuss some aspects of the design and use of our pedagogical platform.

Rosai-Dorfman disease manifesting as an epibulbar ocular tumour.

The authors report a rare case of extranodal Rosai-Dorfman disease without systemic involvement. A 14-year-old girl presented with a slowly progressive, non-tender, well-circumscribed, perilimbal nodule in the right eye. Excisional biopsy was performed and histopathologic and immunohistochemical analysis established the diagnosis. Systemic evaluation revealed no other masses. After complete excision of the epibulbar lesion, the patient is asymptomatic and remains on regular follow up with no signs of recurrence. Rosai-Dorfman disease is an infrequent, benign histiocytic disorder that can rarely manifest as an exclusive extranodal mass. We report a case of solitary epibulbar Rosai-Dorfman disease, successfully treated with complete surgical excision of the lesion.

Evaluation of Inter-Observer Reliability of Animal Welfare Indicators: Which Is the Best Index to Use?

This study focuses on the problem of assessing inter-observer reliability (IOR) in the case of dichotomous categorical animal-based welfare indicators and the presence of two observers. Based on observations obtained from Animal Welfare Indicators (AWIN) project surveys conducted on nine dairy goat farms, and using udder asymmetry as an indicator, we compared the performance of the most popular agreement indexes available in the literature: Scott's π, Cohen's k, kPABAK, Holsti's H, Krippendorff's α, Hubert's Γ, Janson and Vegelius' J, Bangdiwala's B, Andrés and Marzo's ∆, and Gwet's γ(AC1). Confidence intervals were calculated using closed formulas of variance estimates for π, k, kPABAK, H, α, Γ, J, ∆, and γ(AC1), while the bootstrap and exact bootstrap methods were used for all the indexes. All the indexes and closed formulas of variance estimates were calculated using Microsoft Excel. The bootstrap method was performed with R software, while the exact bootstrap method was performed with SAS software. k, π, and α exhibited a paradoxical behavior, showing unacceptably low values even in the presence of very high concordance rates. B and γ(AC1) showed values very close to the concordance rate, independently of its value. Both bootstrap and exact bootstrap methods turned out to be simpler compared to the implementation of closed variance formulas and provided effective confidence intervals for all the considered indexes. The best approach for measuring IOR in these cases is the use of B or γ(AC1), with bootstrap or exact bootstrap methods for confidence interval calculation.

Selecting Indicators to Monitor and Assess Environmental Health in a Portuguese Urban Setting: A Participatory Approach.

Environmental health (EH) is influenced by complex interactions between health and the built and natural environments, there being little research on its specificities in urban settings. The use of suitable indicators to monitor and assess EH is fundamental in informing evidence-based interventions at the local level. A participatory approach to selecting indicators to inform the monitoring and assessment of EH in Lisbon is herein considered. Evidence derived from a systematic review of literature and data from Lisbon and Portuguese databases were analyzed by 12 Portuguese experts in individual semi-structured interviews. The interviews aimed at identifying relevant indicators and important emerging issues in the Lisbon urban setting. The outputs from the interviews were validated by a two-round Web-Delphi process in which panelists (22 experts) from different areas of expertise expressed their views regarding the relevance of the indicators for the analysis of EH in urban settings. Seventeen indicators were validated in the Web-Delphi process. High participation achieved along this process supports the view that this participatory approach was useful for validation. Results from the adopted participatory approach point out gaps in the collection of noise and mobility indicators data and raise emerging issues on housing indicators that require further research. The results also suggest the need for local action to improve indicators and tools in order to help the monitorization of EH in urban contexts. The adopted participatory approach can be replicated for other Portuguese and European urban settings.

Myotendinous junction tear of the anterior bundle of the supraspinatus muscle-a rare pattern of injury involving rotator cuff muscles.

Myotendinous junction injuries are rare and often present with distinctive imaging findings that should be differentiated from purely tendinous degenerative ruptures. Myotendinous junction tears are common in the lower limb but rarely involve rotator cuff muscles. Considering rotator cuff muscles, the infraspinatus and supraspinatus muscles are the most frequently implicated. The intrinsic anatomy of the supraspinatus muscle gives it a greater contractile force and consequently a propensity for rupture. It is composed of two bundles: anterior and posterior (with the latest further divided in a deep anterior, a medial and a superficial posterior portion). These two components have distinctive anatomy with the anterior bundle having a long intramuscular tendon and bipennate configuration and the posterior bundle having a smaller intramuscular tendon and parallel muscle fibres. This distinctive anatomy grants a greater contractile force to the anterior bundle of the supraspinatus muscle and for this reason it is more prone to myotendinous rupture. This type of injury has been associated with a rapid progression to severe fatty infiltration and should be differentiated from purely tendinous tears that are more frequent and associated with degenerative changes. Myotendinous tears occur centrally located in the muscle belly and are not associated with full thickness tears of the distal tendon attachment.

Multi-target optimization of solid phase microextraction to analyse key flavour compounds in wort and beer.

Despite the literature comprises numerous studies dealing with the analysis of wort and beer flavour-related compounds by HS-SPME followed by GC-MS quantification, no generalized consensus exists regarding the optimal conditions for the extraction procedure. The complex chemistry nature of these matrices, the number of analytes, as well as the number and interactions among parameters affecting the extraction performance, requires the adoption of optimal experimental design protocols. This aspect is often overlooked and often not properly addressed in practice. Therefore, in the present work, the optimal conditions under which a range of wort and beer analytes can be extracted and quantified were analysed. The optimal extraction conditions were presented at two levels of aggregation: global (untargeted) and key-flavour analysis. Experimental data was generated by Definitive-Screening-Design, followed by model development and optimization. Both approaches were compared and critically analysed. For vicinal-diketones group, a complete validation study for the optimal conditions is presented.

Nutritional and Phytochemical Composition of Vaccinium padifolium Sm Wild Berries and Radical Scavenging Activity.

Blueberries have a well-deserved reputation as a potential functional food, supported by studies which have identified and quantified various nutrients and bioactive phytochemicals with known benefits for human diet and health. Wild blueberries have attracted particular attention due to the levels and concentrations of those phytonutrients. This study aims to evaluate for the first time the chemical composition of Madeira Island's endemic Vaccinium padifolium Sm wild berry. Results show that this fruit contains high values of total soluble phenolic content (around 4 g GAE kg-1 FW), as well as significant values of total monomeric anthocyanin content (around 3 g eq. cyanidin kg-1 FW) and DPPH scavenging activity (around 86.72%). Additionally, results reveal that this fruit has water content of about 88% as well as low sugar content (17.98 and 29.73 g kg-1 for glucose and fructose, respectively). Results also confirm that this wild blueberry is a good source of dietary fiber, fat and minerals. The high level of terpenoid compounds stands out in the aroma profile analysis. PRACTICAL APPLICATION: This study is in line with the efforts of the scientific community to identify new sources of phytonutrients that are beneficial to human health, characterizing the wild Madeira blueberry in terms of phytonutrients that suggest there may be health benefits associated with its consumption. The findings of this research are very important for both the commercial and agricultural sectors that produce this fruit, and for consumers who seek phytonutrient-rich foods.

Optimal design of experiments applied to headspace solid phase microextraction for the quantification of vicinal diketones in beer through gas chromatography-mass spectrometric detection.

Vicinal diketones, namely diacetyl (DC) and pentanedione (PN), are compounds naturally found in beer that play a key role in the definition of its aroma. In lager beer, they are responsible for off-flavors (buttery flavor) and therefore their presence and quantification is of paramount importance to beer producers. Aiming at developing an accurate quantitative monitoring scheme to follow these off-flavor compounds during beer production and in the final product, the head space solid-phase microextraction (HS-SPME) analytical procedure was tuned through experiments planned in an optimal way and the final settings were fully validated. Optimal design of experiments (O-DOE) is a computational, statistically-oriented approach for designing experiences that are most informative according to a well-defined criterion. This methodology was applied for HS-SPME optimization, leading to the following optimal extraction conditions for the quantification of VDK: use a CAR/PDMS fiber, 5 ml of samples in 20 ml vial, 5 min of pre-incubation time followed by 25 min of extraction at 30 °C, with agitation. The validation of the final analytical methodology was performed using a matrix-matched calibration, in order to minimize matrix effects. The following key features were obtained: linearity (R(2) > 0.999, both for diacetyl and 2,3-pentanedione), high sensitivity (LOD of 0.92 µg L(-1) and 2.80 µg L(-1), and LOQ of 3.30 µg L(-1) and 10.01 µg L(-1), for diacetyl and 2,3-pentanedione, respectively), recoveries of approximately 100% and suitable precision (repeatability and reproducibility lower than 3% and 7.5%, respectively). The applicability of the methodology was fully confirmed through an independent analysis of several beer samples, with analyte concentrations ranging from 4 to 200 g L(-1).

Fisher Grading Scale and Cognitive Deficits ­ Literature Review

Subarachnoid hemorrhage (SAH) accounts for 5 to 10% of all types of stroke, with rupture of brain aneurysms being related to deficits in memory, executive functions, and language. Changes in brain functions appear to be related to the presence of blood in the subarachnoid space, and the Fisher Scale (FS) correlates the amount of blood identified on computed tomography (CT). This paper presents a literature review of the association of FS with cognitive deficits secondary to aneurysmal subarachnoid hemorrhage (aSAH), using PubMed. The attempt to correlate the amount of blood identified in the CT with the development of cognitive alterations presents conflicting data. It was evidenced that some of the studies did not perform cognitive tests, or did not show differences between the scores of FS due to sample difficulty. The FS, even with its limitations and imperfections, seems to be a safe and easily reproducible way to predict neurological, cognitive or neuropsychological deficits, in view of its routine use when analyzing patients with aSAH.

Responsiveness and interpretability of the Portuguese version of the Quebec Back Pain Disability Scale in patients with chronic low back pain.

STUDY DESIGN: A prospective cohort study with a 6-week follow-up of patients with chronic low back pain undergoing physiotherapy. OBJECTIVE: To examine the responsiveness of the Portuguese version of the Quebec Back Pain Disability Scale (QBPDS-PT), and to determine the minimal clinically important difference, minimal detectable change (MDC), and floor/ceiling effects. SUMMARY OF BACKGROUND DATA: Measuring change over time is critical to assess the effectiveness of a physiotherapy intervention or to distinguish individual differences in response to treatment. METHODS: One hundred thirty-two patients were recruited from 16 outpatient clinics in 7 different regions of Portugal. A final sample of 120 patients completed the QBPDS-PT twice: at the baseline and after 6 weeks of physiotherapy treatment. The patient global impression of change scale was used as an external criterion measure to distinguish between improved or nonimproved patients' scores between baseline and follow-up. The responsiveness of the QBPDS-PT was assessed through correlation coefficient and receiver operating characteristics curves. The minimal clinically important difference was estimated by the receiver operating characteristics curve method and the MDC through the standard error of measurement. RESULTS: The scale revealed moderate responsiveness (ρ = 0.426 and area under the curve = 0.741; 95% confidence interval: 0.645-0.837). The MDC achieved 19 points, whereas the minimal clinically important difference was found to be 6.5 points (area under the curve = 0.741, sensitivity = 72%, specificity = 71%). A floor effect was founded with 15.8% of the participants reporting values within the MDC at the lower end of the available range of scores. For the highest baseline scores of QBPDS-PT (≥34 points) the optimal cutoff point was found to be 10.5 points (area under the curve = 0.738, sensitivity = 73%, specificity = 67%). CONCLUSION: The QBPDS-PT demonstrated moderate levels of responsiveness, and is recommended to measure change in disability in patients with chronic low back pain after physiotherapy intervention. LEVEL OF EVIDENCE: N/A.

Comparative study of conjunctival limbal transplantation not associated with the use of amniotic membrane transplantation for treatment of total limbal deficiency secondary to chemical injury.

PURPOSE: The aim of this study was to compare the outcome of conjunctival limbal transplantation with and without the use of amniotic membrane (AM) transplantation for the treatment of limbal deficiency after chemical burns to the eyes. METHODS: This is a retrospective, comparative, interventional case series that included 34 eyes (34 patients) with total limbal deficiency after chemical burns, who were submitted to conjunctival limbal transplantation. Two groups were formed: group 1 (15 eyes) limbal transplantation associated with AM transplantation and group 2 (19 eyes) only limbal transplantation. Success and failure rates, epithelialization time, and visual acuity were compared between the 2 groups. RESULTS: The mean follow-up period was 19.71 ± 5.6 months in group 1 and 18.26 ± 7.78 months in group 2. The proportion of conjunctival limbal autograft and living-related conjunctival limbal allograft was similar in both groups (P = 0.914). Time until complete epithelialization of the corneal surface was significantly longer in group 1 (P = 0.007). Graft survival was similar in both groups (P = 0.581). Failure rate was also similar in both groups (P = 0.232). The most common cause of failure was transplanted stem cell depletion in group 1 (20% of cases) and rejection in group 2 (10.5%). The visual acuity improved postoperatively in 12 eyes (80%) in group 1 and 16 (84.2%) in group 2 (P = 0.430). CONCLUSIONS: Results with the use of AM associated with conjunctival limbal transplantation in ocular surface reconstruction were similar to those obtained with limbal transplantation alone. Both techniques were found to be satisfactory for ocular surface reconstruction in patients with total limbal deficiency after chemical burns.

Electrical signaling in control of ocular cell behaviors.

Epithelia of the cornea, lens and retina contain a vast array of ion channels and pumps. Together they produce a polarized flow of ions in and out of cells, as well as across the epithelia. These naturally occurring ion fluxes are essential to the hydration and metabolism of the ocular tissues, especially for the avascular cornea and lens. The directional transport of ions generates electric fields and currents in those tissues. Applied electric fields affect migration, division and proliferation of ocular cells which are important in homeostasis and healing of the ocular tissues. Abnormalities in any of those aspects may underlie many ocular diseases, for example chronic corneal ulcers, posterior capsule opacity after cataract surgery, and retinopathies. Electric field-inducing cellular responses, termed electrical signaling here, therefore may be an unexpected yet powerful mechanism in regulating ocular cell behavior. Both endogenous electric fields and applied electric fields could be exploited to regulate ocular cells. We aim to briefly describe the physiology of the naturally occurring electrical activities in the corneal, lens, and retinal epithelia, to provide experimental evidence of the effects of electric fields on ocular cell behaviors, and to suggest possible clinical implications.