Development of age-related maculopathy: a histochemical and molecular approach

Age-related maculopathy (ARM) is a severe threat to the visual ability of people over 65 years of age. In the late stages of ARM, called age-related macular degeneration (AMD), photoreceptor cells gradually disappear. New vessels growing beneath the retina may complicateb the disease; this is called âwetâ or neovascular AMD. Knowledge about causes and pathogenesis of this eye disease could lead to therapies, and probably even more important, to strategies that prevent the disease from occurring. The purpose of this thesis was to study several of many molecular changes that occur during the development of ARM. Growth factors play a role in choroidal neovascularization. With advancing age, the thickness of the retina decreases. Little is known about the way cells disappear during this process. Apoptosis was studied in the macula of rhesus monkeys of different ages. The findings indicate that apoptosis in the primate macula occurs at all ages at similar rate, possibly increasing in the oldest age group, and may account for the decreasing thickness of the primate macula with age. It appears to be unlikely that Fas-ligand (FasL) expressed on retinal pigment epithelium controls the extension of choroidal neovascularization. Several growth factors could be involved in the pathogenesis of neovascular AMD. The results may point towards a role of the Insulinlike Growth Factors in the pathogenesis of neovascular AMD. Somatostatin reduces newly formed vessels by inhibiting the growth hormone/insulin-like growth factor axis and also has a direct anti-proliferative effect on various cell types involved in angiogenesis. It is demonstrated that most early-formed choroidal neovascularization in eyes of patients with AMD express sst2A, which is a receptor for somatostatin. The sst2A receptor binds potential anti-angiogenic somatostatin-analogues like octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of neovascular AMD

The preferences of users of electronic medical records in hospitals: Quantifying the relative importance of barriers and facilitators of an innovation

Background: Currently electronic medical records (EMRs) are implemented in hospitals, because of expected benefits for quality and safety of care. However the implementation processes are not unproblematic and are slower than needed. Many of the barriers and facilitators of the adoption of EMRs are identified, but the relative importance of these factors is still undetermined. This paper quantifies the relative importance of known barriers and facilitators of EMR, experienced by the users (i.e., nurses and physicians in hospitals).Methods: A discrete choice experiment (DCE) was conducted among physicians and nurses. Participants answered ten choice sets containing two scenarios. Each scenario included attributes that were based on previously identified barriers in the literature: data entry hardware, technical support, attitude head of department, performance feedback, flexibility of interface, and decision support. Mixed Multinomial Logit analysis was used to determine the relative importance of the attributes.Results: Data on 148 nurses and 150 physicians showed that high flexibility of the interface was the factor with highest relative importance in their preference to use an EMR. For nurses this attribute was followed by support from the head of department, presence of performance feedback from the EMR and presence of decisions support. While for physicians this ordering was different: presence of decision support was relatively more important than performance feedback and support from the head of department.Conclusion: Considering the prominent wish of all the intended users for a flexible interface, currently used EMRs only partially comply with the needs of the users, indicating the need for closer incorporation of user needs during development stages of EMRs. The differences in priorities amongst nurses and physicians show that different users have different needs during the implementation of innovations. Hospital management may use this information to design implementation trajectories to fit the needs of various user groups

Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration

PURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose of our study is to investigate the expression of somatostatin receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human macula, and to study sst2A in different stages of age-related maculopathy (ARM), because of the potential anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal neovascular [CNV] membranes) of 15 patients with eyes at different stages of ARM were used for immunohistochemistry. Formaldehyde-fixed paraffin-embedded slides were incubated with a polyclonal anti-human sst2A antibody. mRNA expression of five ssts and somatostatin was determined in the posterior pole of three normal human eyes by reverse transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical expression of sstA in newly formed endothelial cells and fibroblast-like cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1, 2A, and 3, as well as somatostatin, was present in the normal posterior pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype 2A was observed in normal human macula, and subtypes 1 and 3 and somatostatin are also present. sst2A receptors bind potential anti-angiogenic somatostatin analogues such as octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of CNV in ARM

Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration

PURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose of our study is to investigate the expression of somatostatin receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human macula, and to study sst2A in different stages of age-related maculopathy (ARM), because of the potential anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal neovascular [CNV] membranes) of 15 patients with eyes at different stages of ARM were used for immunohistochemistry. Formaldehyde-fixed paraffin-embedded slides were incubated with a polyclonal anti-human sst2A antibody. mRNA expression of five ssts and somatostatin was determined in the posterior pole of three normal human eyes by reverse transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical expression of sstA in newly formed endothelial cells and fibroblast-like cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1, 2A, and 3, as well as somatostatin, was present in the normal posterior pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype 2A was observed in normal human macula, and subtypes 1 and 3 and somatostatin are also present. sst2A receptors bind potential anti-angiogenic somatostatin analogues such as octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of CNV in ARM

Acceptance of vaccinations in pandemic outbreaks: A discrete choice experiment

Background: Preventive measures are essential to limit the spread of new viruses; their uptake is key to their success. However, the vaccination uptake in pandemic outbreaks is often low. We aim to elicit how disease and vaccination characteristics determine preferences of the general public for new pandemic vaccinations. Methods: In an internet-based discrete choice experiment (DCE) a representative sample of 536 participants (49% participation rate) from the Dutch population was asked for their preference for vaccination programs in hypothetical communicable disease outbreaks. We used scenarios based on two disease characteristics (susceptibility to and severity of the disease) and five vaccination program characteristics (effectiveness, safety, advice regarding vaccination, media attention, and out-of-pocket costs). The DCE design was based on a literature review, expert interviews and focus group discussions. A panel latent class logit model was used to estimate which trade-offs individuals were willing to make. Results: All above mentioned characteristics proved to influence respondents' preferences for vaccination. Preference heterogeneity was substantial. Females who stated that they were never in favor of vaccination made different trade-offs than males who stated that they were (possibly) willing to get vaccinated. As expected, respondents preferred and were willing to pay more for more effective vaccines, especially if the outbreak was more serious (€6-€39 for a 10% more effective vaccine). Changes in effectiveness, out-of-pocket costs and in the body that advises the vaccine all substantially influenced the predicted uptake. Conclusions: We conclude that various disease and vaccination program characteristics influence respondents' preferences for pandemic vaccination programs. Agencies responsible for preventive measures during pandemics can use the knowledge that out-of-pocket costs and the way advice is given affect vaccination uptake to improve their plans for future pandemic outbreaks. The preference heterogeneity shows that information regarding vaccination needs to be targeted differently depending on gender and willingness to get vaccinated