Artificial vision: the effectiveness of the OrCam in patients with advanced inherited retinal dystrophies

Purpose To investigate the impact of the OrCam MyEye 2.0 (OrCam) on the quality of life and rehabilitation needs in patients with advanced retinitis pigmentosa (RP) or cone-rod dystrophies (CRD). The OrCam is a wearable low-vision aid that converts visual information to auditive feedback (e.g. text-to-speech, barcode and facial recognition). Methods Patients with a clinical diagnosis of RP (n = 9, 45%) or CRD (n = 11; 55%), and a best-corrected visual acuity of <= 20/400 Snellen were invited to participate in this study. Questionnaires were administered at baseline and after 5.2 (standard deviation +/- 1.5) weeks, which included the Dutch version of the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ), the Participation and Activity Inventory (PAI) and the OrCam Function Questionnaire (OFQ). Results Following OrCam testing, significant improvements were observed in the 'near activities' subscale of the NEI-VFQ (p < 0.001); the 'visual functioning' subscale of the re-engineered NEI-VFQ (p = 0.001); the 'reading' rehabilitation goal of the PAI (p = 0.005) and the overall score of the OFQ (p < 0.001). The observed changes in questionnaire scores did not differ between phenotypes. Advantages and limitations of the OrCam were reported by patients. Three patients (15%) continued rehabilitation with the OrCam after completion of this study. Conclusions The OrCam mainly improves reading domains in patients with advanced stages of RP or CRD. Further improvements in the OrCam are needed to address current limitations, which may enhance its utility for patients with RP or CRD.Ophthalmic researc

The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome

Background Mast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS. Methods 60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment. After the initial barostat, patients were randomised to receive ketotifen or placebo. IBS symptoms and health-related quality of life were scored. In addition, mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers. Results Ketotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity. This effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers. Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers. Histamine and tryptase release were not altered by ketotifen. Conclusions This study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity, reduces IBS symptoms and improves health-related quality of life. Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H-1 receptor antagonism remains to be further investigate

Reconfiguring tissue banking consent through enrichment of a restricted debate

Tissue banks are thought to be an essential resource for medical research in the post-genomic age. Collections of tissue, usually removed in the course of diagnostic or therapeutic procedures, enable laboratory-based epidemiological studies to be carried out, linking abnormalities in the tissue to disease aetiology, prognosis and treatment responsiveness. There are, however, a number of technical, regulatory and ethical concerns that challenge those wishing to engage in tissue banking research. It is becoming increasingly apparent that tissue banking research is not without risk of harms, even though there is no direct physical risk to donors. This is because, in order to be most useful, banked specimens need to be linked to personal information about tissue donors and this poses the risk of inadvertent disclosure of personal─ particularly genetic─ information to those who might exploit such information (eg. insurance companies and employers). Furthermore, the long-term storage of specimens, and the impossibility of predicting all potential types of research programs for which they might be useful, raises the possibility that future projects will be carried out that are unacceptable to some (past) tissue donors. The ethical principles of autonomy and respect for persons demand that research subjects be informed of such risks and of the nature of the research, and that they participate willingly. On the other hand, there is a desire for science to progress unhindered by stringent consent requirements. For these reasons, a debate has emerged in the academic (bioethical and biomedical) literature and in the legal (law reform) sphere over what would constitute adequate consent. Despite an extensive discourse, it is still unclear whether it is permissible to carry out research on archival tissue that was originally taken for diagnostic purposes and whether project-specific (as opposed to open-ended) consent is required for research on tissue collected today. This lack of clarity is of concern to researchers, ethics committees and research subjects, all of whom recognise the importance of tissue banking research, yet fear that current consent procedures may be ethically or legally inadequate. Thus it is important that the consent dilemma be resolved as quickly and definitively as possible. Ongoing controversy and regulatory ambiguity are appropriate when morally contentious issues are at stake, and their existence does not, on its own, signal any flaws in the discourse process. There are, however, two reasons to suspect that the current 'consent to tissue banking' debate, as portrayed in the academic literature and law reform documentation, is problematic. Firstly, the debate appears to be mired in an intractable conflict between those who want to maximise personal autonomy through stringent consent requirements, and those who want the scientific endeavour to progress in a manner that is unconstrained by what are viewed as arduous consent procedures. Secondly, the possible practical options (consent models) being generated by the debate are all limited because they are underpinned by a restricted notion of consent as an individualistic, legalistic and static activity, without consideration of any alternative conceptualisations of consent. Through a thematic analysis of the current 'consent to tissue banking' debate in the academic and law reform literature (Section 3), this thesis shows that debate is essentially occurring between those who see individual autonomy (and stringent consent) as being of primary importance, and those who see unimpeded, market-driven scientific progress as the more important social good, which should not be impeded by unnecessarily stringent consent. Thematic analysis also confirms the existence of the two problems described above, and a failure of those engaged in the debate to reflect on, and challenge, the value-level assumptions underpinning their arguments and those of their opponents. It is argued that this lack of reflection accounts for the two problems: • Firstly, it precludes recognition of the cause of─ and, therefore, ways of resolving─ the intractable conflict at the centre of the debate. Value-level reflection shows that this is a result of the logical and moral conflict within western liberalism, between two modernist goods: individual freedom and scientific progress. • Secondly, it precludes the generation of varied conceptions of consent. Value-level reflection shows that the current range of consent models is restricted to procedures which are individualistic, abstract, static and legalistic, since they are underpinned by western liberal notions of autonomy and scientific progress. This recognition paves the way to consideration of alternative notions of autonomy, scientific progress and, therefore, consent, such as those derived from communitarian and feminist systems of values. A conceptually enriched model of tissue banking consent is then developed (Section 4). This model incorporates dominant (liberal) conceptions of autonomy and scientific progress as well as alternative notions of autonomy and scientific progress espoused by communitarian and feminist systems of values. It is argued that this conceptually-enriched model provides a practical solution to the two problems associated with the standard 'consent to tissue banking' debate. In relation to the philosophically intractable conflict─ or what is termed the 'modernist dilemma'─ between those privileging autonomy and those privileging scientific progress, it shows how the two apparently conflicting 'modernist' goods can both be accommodated at a practical level, thus making the 'consent to tissue banking' debate more tractable and fruitful. In relation to the restricted range of consent models being generated by the current debate, it provides new insights into the ways in which consent might be obtained such that a broader range of community values can be accommodated. More specifically, it stimulates the construction of a model that 1) involves communities, as opposed to merely individuals, in all stages of the scientific process; 2) is flexible and able to adapt consent procedures to specific contexts, rather than predefining procedures in abstract terms; and 3) is transactional and relational rather than static and legalistic. This outcome has interesting philosophical as well as practical implications. It shows that despite apparently unresolved, and possibly irresolvable, normative-level conflicts between the two modernist elements of western liberalism (autonomy and scientific progress), and between liberal, feminist and communitarian systems of values, a multi-perspectival, inclusive, model-building approach provides a practical solution that circumvents these normative-level conflicts

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals

Background: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. Aim: To determine the prevalence of Do No

Evaluation of the performance of algorithms mapping EORTC QLQ-C30 onto the EQ-5D index in a metastatic colorectal cancer cost-effectiveness model

BACKGROUND: Cost-effectiveness models require quality of life utilities calculated from generic preference-based questionnaires, such as EQ-5D. We evaluated the performance of available algorithms for QLQ-C30 conversion into EQ-5D-3L based ut

Ultrasound markers for prediction of complex gastroschisis and adverse outcome: longitudinal prospective nationwide cohort study

Objectives: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. Methods: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. Results: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter ≥ 97.7th percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02–2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). Conclusions: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date