A Concise and Useful Guide to Understand How Alpha1 Adrenoceptor Antagonists Work.

Adrenoceptors are the receptors for catecholamines, adrenaline, and noradrenaline. They are divided in α (α1 and α2) and ß (ß1, ß2 and ß3). α1-adrenoceptors are subdivided in α1A, α1B and α1D. Most tissues express mixtures of α1-adrenoceptors subtypes, which appear to coexist in different densities and ratios, and in most cases, their responses are probably due to the activation of more than one type. The three subtypes of α1-adrenoceptors are G-protein-coupled receptors (GPCR), specifically coupled to Gq/11. Additionally, the activation of these receptors may activate other signaling pathways or different components of these pathways, which leads to a great variety of possible cellular effects. The first clinically used α1 antagonist was Prazosin for Systemic Arterial Hypertension (SAH). It was followed by its congeners, Terazosin and Doxazosin. Nowadays, there are many classes of α-adrenergic antagonists with different selectivity profiles. In addition to SAH, the α1-adrenoceptors are used to treat Benign Prostatic Hyperplasia (BPH) and urolithiasis. This antagonism may be part of the mechanism of action of tricyclic antidepressants. Moreover, the activation of these receptors may lead to adverse effects such as orthostatic hypotension, similar to what happens with antidepressants and with some antipsychotics. Structure-activity relationships can explain, in part, how antagonists work and how selective they can be for each one of the subtypes. However, it is necessary to develop new molecules which antagonize the α1- adrenoceptors or make chemical modifications in these molecules to improve the selectivity and pharmacokinetic profile and/or reduce the adverse effects of known drugs.

Education Outcomes of Children Born Late Preterm: A Retrospective Whole-Population Cohort Study.

BACKGROUND: Early life exposures can have an impact on a child's developmental trajectory and children born late preterm (34-36 weeks gestational age) are increasingly recognized to have health and developmental setbacks that extend into childhood. OBJECTIVES: The purpose of this study was to assess whether late preterm birth was associated with poorer developmental and educational outcomes in the early childhood period, after controlling for health and social factors. METHODS: We conducted a retrospective cohort study using administrative databases housed at the Manitoba Centre for Health Policy, including all children born late preterm (34-36 weeks gestational age (GA)) and at full-term (39-41 weeks GA) between 2000 and 2005 in urban Manitoba (N = 28,100). Logistic regression was used to examine the association between gestational age (GA) and outcomes, after adjusting for covariates. RESULTS: Adjusted analyses demonstrated that children born late preterm had a higher prevalence of attention deficit hyperactivity disorder (ADHD) (aOR = 1.25, 95% CI [1.03, 1.51]), were more likely to be vulnerable in the language and cognitive (aOR = 1.29, 95% CI [1.06, 1.57]), communication and general knowledge (aOR = 1.24, 95% CI [1.01, 1.53]), and physical health and well-being (aOR = 1.27, 95% CI [1.04, 1.53]) domains of development at kindergarten, and were more likely to repeat kindergarten or grade 1 (aOR = 1.52, 95% CI [1.03, 2.25]) compared to children born at term. They did not differ in receipt of special education funding, in social maturity or emotional development at kindergarten, and in reading and numeracy assessments in the third grade. CONCLUSIONS: Given that the late preterm population makes up 75% of the preterm population, their poorer outcomes have implications at the population level. This study underscores the importance of recognizing the developmental vulnerability of this population and adequately accounting for the social differences between children born late preterm and at term.

Evaluation and refinement of a handheld health information technology tool to support the timely update of bedside visual cues to prevent falls in hospitals.

AIM: To evaluate clinicians' perspectives, before and after clinical implementation (i.e. trial) of a handheld health information technology (HIT) tool, incorporating an iPad device and automatically generated visual cues for bedside display, for falls risk assessment and prevention in hospital. METHODS: This pilot study utilized mixed-methods research with focus group discussions and Likert-scale surveys to elicit clinicians' attitudes. The study was conducted across three phases within two medical wards of the Queen Elizabeth Hospital. Phase 1 (pretrial) involved focus group discussion (five staff) and surveys (48 staff) to elicit preliminary perspectives on tool use, benefits and barriers to use and recommendations for improvement. Phase 2 (tool trial) involved HIT tool implementation on two hospital wards over consecutive 12-week periods. Phase 3 (post-trial) involved focus group discussion (five staff) and surveys (29 staff) following tool implementation, with similar themes as in Phase 1. Qualitative data were evaluated using content analysis, and quantitative data using descriptive statistics and logistic regression analysis, with subgroup analyses on user status (P ≤ 0.05). RESULTS: Four findings emerged on clinicians' experience, positive perceptions, negative perceptions and recommendations for improvement of the tool. Pretrial, clinicians were familiar with using visual cues in hospital falls prevention. They identified potential benefits of the HIT tool in obtaining timely, useful falls risk assessment to improve patient care. During the trial, the wards differed in methods of tool implementation, resulting in lower uptake by clinicians on the subacute ward. Post-trial, clinicians remained supportive for incorporating the tool into clinical practice; however, there were issues with usability and lack of time for tool use. Staff who had not used the tool had less appreciation for it improving their understanding of patients' falls risk factors (odds ratio 0.12), or effectively preventing hospital falls (odds ratio 0.12). Clinicians' recommendations resulted in subsequent technological refinement of the tool, and provision of an additional iPad device for more efficient use. CONCLUSION: This study adds to the limited pool of knowledge about clinicians' attitudes toward health technology use in falls avoidance. Clinicians were willing to use the HIT tool, and their concerns about its usability were addressed in ongoing tool improvement. Including end-users in the development and refinement processes, as well as having high staff uptake of new technologies, is important in improving their acceptance and usage, and in maximizing beneficial feedback to further inform tool development.

Prevalência do tracoma no povoado de Mocambo, Estado do Ceará, Brasil / Prevalence of trachoma in the village of Mocambo, State of Ceara, Brazil

A prevalência de tracoma no povoado de Mocambo, município de Guaraciaba, estado do Ceará, foi estudada de acordo com o novo esquema de classificaçäo do tracoma adotado pela Organizaçäo Mundial da Saúde. Entre os 396 moradores daquele povoado, 46,96% apresentavam algum sinal de lesäo tracomatrosa, sendo 22,22% com tracoma folicular, 21, 71% com cicatrizes tracomatosas na conjuntiva tarsal superior, 2,02% com triquíases e 1,03% com opacidade corneana. O diagnóstico clínico de tracoma folicular foi confirmado laboratorialmente através da imunofluorescência direta pelo anticorpo monoclonal