Outcomes of gonioscopy-assisted transluminal trabeculotomy in pseudoexfoliative glaucoma: 24-month follow-up

AimTo report on outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in eyes with pseudoexfoliative glaucoma (PXG).MethodsProspective, interventional, non-comparative case series. A total of 103 eyes from 84 patients with PXG were enrolled to undergo a 360-degree ab interno trabeculotomy with gonioscopic assistance using either a 5.0 polypropylene suture or an illuminated microcatheter with up to 24 months of follow-up. Main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, success rate (IOP reduction ≥20% from baseline or IOP between 6 and 21 mm Hg, without further glaucoma surgery) and complication rate.ResultsMean preoperative IOP was 27.1 mm Hg (95% CI 25.5 to 28.7) using 2.9 (SD 1.1) glaucoma medications which decreased postoperatively to 13.0 mm Hg (95% CI 11.5 to 14.4) and 1.0 (SD 1.1) medications at 24 months (p&lt;0.001). Success rate was 89.2% at 24 months of follow-up, and complication rate was 2.9%.ConclusionAt 24 months of follow-up, our results for GATT in PXG demonstrate that this conjunctival sparing procedure effectively lowers IOP and reduces the medications with a low complication rate, in this relatively aggressive glaucoma subtype.</jats:sec

Abnormalities of calcium metabolism and myocardial contractility depression in the failing heart

Heart failure (HF) is characterized by molecular and cellular defects which jointly contribute to decreased cardiac pump function. During the development of the initial cardiac damage which leads to HF, adaptive responses activate physiological countermeasures to overcome depressed cardiac function and to maintain blood supply to vital organs in demand of nutrients. However, during the chronic course of most HF syndromes, these compensatory mechanisms are sustained beyond months and contribute to progressive maladaptive remodeling of the heart which is associated with a worse outcome. Of pathophysiological significance are mechanisms which directly control cardiac contractile function including ion- and receptor-mediated intracellular signaling pathways. Importantly, signaling cascades of stress adaptation such as intracellular calcium (Ca2+) and 3′-5′-cyclic adenosine monophosphate (cAMP) become dysregulated in HF directly contributing to adverse cardiac remodeling and depression of systolic and diastolic function. Here, we provide an update about Ca2+ and cAMP dependent signaling changes in HF, how these changes affect cardiac function, and novel therapeutic strategies which directly address the signaling defects

'The Words Will Pass with the Blowing Wind': Staff and Parent Views of the Deferred Consent Process, with Prior Assent, Used in an Emergency Fluids Trial in Two African Hospitals

Objective To document and explore the views and experiences of key stakeholders regarding the consent procedures of an emergency research clinical trial examining immediate fluid resuscitation strategies, and to discuss the implications for similar trials in future. Methods A social science sub-study of the FEAST (Fluid Expansion As Supportive Therapy) trial. Interviews were held with trial team members (n = 30), health workers (n = 15) and parents (n = 51) from two purposively selected hospitals in Soroti, Uganda, and Kilifi, Kenya. Findings Overall, deferred consent with prior assent was seen by staff and parents as having the potential to protect the interests of both patients and researchers, and to avoid delays in starting treatment. An important challenge is that the validity of verbal assent is undermined when inadequate initial information is poorly understood. This concern needs to be balanced against the possibility that full prior consent on admission potentially causes harm through introducing delays. Full prior consent also potentially imposes worries on parents that clinicians are uncertain about how to proceed and that clinicians want to absolve themselves of any responsibility for the child’s outcome (some parents’ interpretation of the need for signed consent). Voluntariness is clearly compromised for both verbal assent and full prior consent in a context of such vulnerability and stress. Further challenges in obtaining verbal assent were: what to do in the absence of the household decision-maker (often the father); and how medical staff handle parents not giving a clear agreement or refusal. Conclusion While the challenges identified are faced in all research in low-income settings, they are magnified for emergency trials by the urgency of decision making and treatment needs. Consent options will need to be tailored to particular studies and settings, and might best be informed by consultation with staff members and community representatives using a deliberative approach

Social and Behavioural Aspects of Child and Adolescent Participation in HIV Vaccine Trials.

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A Comparison of the Quality of Informed Consent for Clinical Trials of an Experimental Hookworm Vaccine Conducted in Developed and Developing Countries

<div><p>Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed consent process of a series of clinical trials of an investigational hookworm vaccine that were performed in Brazil and the United States. A standardized questionnaire was used to assess the ethical quality of the informed consent process in a series of Phase 1 clinical trials of the <i>Na</i>-GST-1/Alhydrogel hookworm vaccine that were conducted in healthy adults in Brazil and the United States. In Brazil, the trial was conducted at two sites, one in the hookworm non-endemic urban area of Belo Horizonte, Minas, and one in the rural, resource-limited town of Americaninhas, both in the state of Minas Gerais; the American trial was conducted in Washington, DC. A 32-question survey was administered after the informed consent document was signed at each of the three trial sites; it assessed participants’ understanding of information about the study presented in the document as well as the voluntariness of their decision to participate. 105 participants completed the questionnaire: 63 in Americaninhas, 18 in Belo Horizonte, and 24 in Washington, DC. Overall knowledge about the trial was suboptimal: the mean number of correct answers to questions about study objectives, methods, duration, rights, and potential risks and benefits, was 45.6% in Americaninhas, 65.2% in Belo Horizonte, and 59.1% in Washington, DC. Although there was no difference in the rate of correct answers between participants in Belo Horizonte and Washington, DC, there was a significant gap between participants at these two locations compared to Americaninhas (p = 0.0002 and p = 0.0001, respectively), which had a lower percentage of correct answers. Attitudes towards participating in the clinical trial also differed by site: while approximately 40% had doubts about participating in Washington, DC and Belo Horizonte, only 1.5% had concerns in Americaninhas. Finally, in Belo Horizonte and Washington, high percentages cited a desire to help others as motivation for participating, whereas in Americaninhas, the most common reason for participating was personal interest (p = 0.001). Understanding of information about a Phase 1 clinical trial of an experimental hookworm vaccine following informed consent was suboptimal, regardless of study site. Although overall there were no differences in knowledge between Brazil and the US, a lower level of understanding about the trial was seen in participants at the rural, resource-limited Brazilian site. These findings demonstrate the need for educational interventions directed at potential clinical trial participants, both in developing and developed countries, in order to improve understanding of the informed consent document.</p></div

Cardiac Sodium Channel (Dys)Function and Inherited Arrhythmia Syndromes

Normal cardiac sodium channel function is essential for ensuring excitability of myocardial cells and proper conduction of the electrical impulse within the heart. Cardiac sodium channel dysfunction is associated with an increased risk of arrhythmias and sudden cardiac death. Over the last 20 years, (combined) genetic, electrophysiological, and molecular studies have provided insight into the (dys)function and (dys)regulation of the cardiac sodium channel under physiological circumstances and in the setting of SCN5A mutations identified in patients with inherited arrhythmia syndromes. Although our understanding of these sodium channelopathies has increased substantially, important issues remain incompletely understood. It has become increasingly clear that sodium channel distribution, function, and regulation are more complicated than traditionally assumed. Moreover, recent evidence suggests that the sodium channel may play additional, as of yet unrecognized, roles in cardiomyocyte function, which in turn may ultimately also impact on arrhythmogenesis. In this chapter, an overview is provided of the structure and function of the cardiac sodium channel and the clinical and biophysical characteristics of inherited sodium channel dysfunction. In addition, more recent insights into the electrophysiological and molecular aspects of sodium channel dysregulation and dysfunction in the setting of SCN5A mutations are discussed