Skin Prick Automated Test device offers more reliable allergy test results compared to a manual skin prick test.

BACKGROUND: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of inhalant allergy. A novel device, SPAT or Skin Prick Automated Test, that enables more standardized allergy testing has been developed. Previous research has shown reduced intra-subject variability of histamine wheals by SPAT. OBJECTIVE: This study aimed to evaluate within-test agreement (% of patients with consistent test results) to detect sensitization to common inhalant allergens when a SPT is executed automated by SPAT or by manual SPT (SPMT) procedure. METHODS: The 110 volunteers prospectively enrolled underwent both SPAT and SPMT with 3 pricks of house dust mite, timothy grass and birch, 2 pricks of histamine and 1 prick of glycerol. The proportion of consistent (3x positive â€" 3 x negative) and inconsistent (2x positive/negative â€" 1x positive/negative) test results were analysed. RESULTS: The proportion of inconsistent test results was significantly lower in the SPAT compared to the SPMT group. The delta histamine to control pricks was significantly higher in SPAT compared to SPMT group. Coefficient of variation was lower in SPAT compared to SPMT for house dust mite, timothy grass, birch pollen. Visual analogue scale for discomfort was significantly lower in SPAT compared to SPMT group. CONCLUSION: SPAT showed a 34% reduction in the number of inconsistent test results compared to manual SPT with common inhalant allergens. Patient experience is significantly improved when an allergy test is performed by SPAT compared to a manual SPT.

Comment on Neiser et al. Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA). Int. J. Mol. Sci. 2016, 17, 1185.

All IV iron complexes carry a risk of potentially fatal allergic type hypersensitivity reactions. The mechanism(s) behind these reactions is unknown but the limited data available suggests that classic IgE mediated allergy is exceedingly rare, if ever occurring. Iron-carbohydrate molecules are complex nano-particles and trying to reduce the risk of serious hypersensitivity to antibody binding of an artificial antibody seems meaningless. A recently published analysis of safety data from randomized clinical trials confirms the method reported by Neiser to be useless to predict reaction risk. In conclusion, the study by Neiser et al. is biased, contains no new information, and has no clinical relevance. We are concerned that the association of the authors with a commercial entity has caused a conflict of interest that biases not only the results, but the entire experimental setup against competitors. (Comment on Neiser et al. Int. J. Mol. Sci. 2016, 17, 1185, doi:10.3390/ijms17071185).

Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome.

Two siblings, from a consanguineous Iraqi family, were investigated to identify the underlying genetic cause of their high myopia, esotropia, vitreous changes and cataract. Subsequent investigation identified low molecular weight proteinuria as part of their syndrome. Exome sequencing of one of the probands revealed a new non-synonymous variant in the LRP2 gene. Sanger sequencing confirmed the mutation and segregation in the family. No mutation was identified in COL9A1/2, COL11A1/2, or COL2A1 genes. The variant (c.11483A>G; p.Asp3828Gly) is predicted to be damaging and is conserved among vertebrate species. Mutations in LRP2 have been shown to cause the Donnai-Barrow syndrome (DBS) or facio-oculo-acoustico-renal (FOAR) syndrome, a syndrome associated with facial dysmorphism, ocular anomalies, sensorineural hearing loss, low molecular weight proteinuria, and diaphragmatic hernia and absent corpus callosum, although there is variability in the expression of some features. This family shows a milder phenotype with a predominant eye phenotype similar to the Stickler syndrome and only a few features of the DBS, including microglobulinuria. The presence of microglobulinuria was only detected after molecular results were known. In conclusion, with the identification of a new mutation in LRP2 associated with a predominant eye phenotype similar to the Stickler syndrome, we have broadened the phenotypic spectrum of LRP2 mutations.

Aligning quality of life and guidelines for off-label psychotropic drugs in adults with intellectual disabilities and challenging behaviour.

Introduction: Adults with intellectual disabilities have an increased vulnerability to mental health problems and challenging behaviour. In addition to psychotherapeutic or psychoeducational methods, off-label pharmacotherapy, is a commonly used treatment modality. Objective: The aim of this study was to establish evidence-based guideline recommendations for the responsible prescription of off-label psychotropic drugs, in relation to Quality of Life (QoL). Method: A list of guidelines was selected, and principles were established based on international literature, guideline review and expert evaluation. The Delphi method was used to achieve consensus about guideline recommendations among a 58-member international multidisciplinary expert Delphi panel. Thirty-three statements were rated on a 5-point Likert-scale, ranging from totally disagree to totally agree, in consecutive Delphi rounds. When at least 70% of the participants agreed (score equal or higher than 4), a statement was accepted . Statements without a consensus were adjusted between consecutive Delphi rounds based on feedback from the Delphi panel. Results: Consensus was reached on 4 general:the importance of non-pharmaceutical treatments, comprehensive diagnostics and multidisciplinary treatment. Consensus was reached in 4 rounds on 29 statements. No consensus was reached on 4 statements concerning: freedom-restricting measures, the treatment plan, the evaluation of the treatment plan, and the informed consent. Conclusion: The study led to recommendations and principles for the responsible prescription - aligned with the QoL perspective - of off-label psychotropic drugs for adults with intellectual disabilities and challenging behaviour. Extensive discussion is needed regarding the issues on which there was no consensus to furthering the ongoing development of this guideline.

Family quality of life in 25 Belgian families: quantitative and qualitative exploration of social and professional support domains.

BACKGROUND: This article reports on the results of a study conducted in Belgium on family quality of life situated within a larger project focusing on the development of support strategies for young and adolescent siblings of persons with intellectual disabilities. The objectives of this article are twofold: (1) to present the results of the measures contained in the nine domains of the Family Quality of Life Survey-2006 (FQOLS-2006) from the perspective of parents (quantitative analysis); and (2) to come to a more in-depth understanding of two important domains of the FQOLS-2006 by exploring and comparing the quantitative and qualitative data from open-ended interviews with parents. METHOD: The FQOLS-2006 was completed by the main caregivers of 25 families living in one typical Belgian province. Subsequently, semi-structured interviews with one or both parents were conducted within the same families. Content analysis was carried out on the transcribed interviews using the qualitative software package MaxQDA. RESULTS: A detailed analysis of the quantitative data together with data from the content analysis of the interviews revealed important issues with regard to two family quality of life domains, support from others and support from services. In general, parents were satisfied with the professional support they received, whereas they were more critical of support from others. CONCLUSIONS: The quantitative data from the FQOLS-2006 were supported and further explained by the qualitative data. These findings highlight the importance of adequate professional support, which is a flexible and capable answer to each family's individual needs. The authors warn of the dangers of 'handicapism' and plea for a family-centred support approach that takes the whole family into account. Finally, they indicate the benefits of increased practical-pedagogical support.

Evaluating the inter-respondent (consumer vs. staff) reliability and construct validity (SIS vs. Vineland) of the Supports Intensity Scale on a Dutch sample.

BACKGROUND: Despite various reliability studies on the Supports Intensity Scale (SIS), to date there has not been an evaluation of the reliability of client vs. staff judgments. Such determination is important, given the increasing consumer-driven approach to services. Additionally, there has not been an evaluation of the instrument's construct validity on a non-English speaking sample. This is important as the SIS is currently translated into 13 languages. METHOD: Data were collected in two different samples, using the Dutch translation of the SIS and the Vineland-Z. RESULTS: There was a significant correlation between ratings of staff and consumers on the SIS; however, the relationship between the mean scores of consumer and staff responses indicated significant differences in staff and consumer scores. All correlations between the Vineland-Z domains and the SIS subscales were significant and negative, ranging from -0.37 to -0.89. CONCLUSIONS: Analyses of the inter-respondent reliability suggest that one needs to consider the source of information regarding needed supports carefully. The significant negative correlations between SIS and Vineland-Z reflect that the SIS is measuring a different construct (needed support) than the Vineland-Z (adaptive behaviour). The results of the two studies provide additional support for the etic (universal) properties of the SIS, as both hypotheses were confirmed. In conclusion, SIS users are provided with a wealth of information that can be used for multiple purposes.

S100A4 is upregulated in injured myocardium and promotes growth and survival of cardiac myocytes.

OBJECTIVE: The multifunctional Ca2+-binding protein S100A4 (also known as Mts1 and Fsp1) is involved in fibrosis and tissue remodeling in several diseases including cancer, kidney fibrosis, central nervous system injury, and pulmonary vascular disease. We previously reported that S100A4 mRNA expression was increased in hypertrophic rat hearts and that it has pro-cardiomyogenic effects in embryonic stem cell-derived embryoid bodies. We therefore hypothesized that S100A4 could play a supportive role in the injured heart. METHODS AND RESULTS: Here we verify by quantitative real-time PCR and immunoblotting that S100A4 mRNA and protein is upregulated in hypertrophic rat and human hearts and show by way of confocal microscopy that S100A4 protein, but not mRNA, appears in cardiac myocytes only in the border zone after an acute ischemic event in rat and human hearts. In normal rat and human hearts, S100A4 expression primarily colocalizes with markers of fibroblasts. In hypertrophy elicited by aortic banding/stenosis or myocardial infarction, this expression is increased. Moreover, invading macrophages and leucocytes stain strongly for S100A4, further increasing cardiac levels of S100A4 protein after injury. Promisingly, recombinant S100A4 protein elicited a robust hypertrophic response and increased the number of viable cells in cardiac myocyte cultures by inhibiting apoptosis. We also found that ERK1/2 activation was necessary for both the hypertrophy and survival effects of S100A4 in vitro. CONCLUSIONS: Along with proposed angiogenic and cell motility stimulating effects of S100A4, these findings suggest that S100A4 can act as a novel cardiac growth and survival factor and may have regenerative effects in injured myocardium.

Differential influence of different hepatitis viruses on quality of life in HIV positive patients.

UNLABELLED: HIV-infected individuals are frequently co-infected with different hepatitis viruses. HCV has been associated with impaired quality of life in non-HIV infected patients. Little is known concerning the quality of life in HIV-infected individuals in relation to the different viral co-infections. - PATIENTS AND METHODS: We investigated 250 patients who have answered HIV-SELT and EuroQoL (EQ-5D) questionnaires assessing quality of life. Data on HBsAg, anti-HBc, anti-HCV, and GBV-C-RNA were available for 191, 188, 189, 98 patients, respectively. HCV-RNA was tested in 33 of 35 anti-HCV positive patients. - RESULTS: There was no difference in quality of life in relation to active or past HBV-infection defined by HBsAg (n = 15) and anti-HBc in the absence of HBsAg (n = 84), respectively, for both overall HIV-SELT (p = 0.66, and p = 0.43, respectively) and visual EQ-5D (p = 0.93 and p = 0.64, respectively). However, anti-HCV positivity (n = 35) was associated with significantly impaired quality of life (HIV-SELT overall p<0.001). Importantly, no difference was found in relation to HCV-viraemia in anti-HCV positive patients (p = 0.77). In multivariate analysis anti-HCV positivity, employment status, HIV viral load and GBV-C were relevant to quality of life, with GBV-C being beneficial and HCV being negative. - CONCLUSIONS: While HBV seems to play no role concerning quality of live in HIV-infected patients, the flavi-viruses HCV and GBV-C display opposing influence on quality of life. As quality of life was similarly impaired in HCV-viraemic and HCV-non-viraemic anti-HCV positive patients but better in GBV-C viraemic patients, this should be taken into account in the indication case of planned interferon therapy.

Expression profiling reveals differences in metabolic gene expression between exercise-induced cardiac effects and maladaptive cardiac hypertrophy.

While cardiac hypertrophy elicited by pathological stimuli eventually leads to cardiac dysfunction, exercise-induced hypertrophy does not. This suggests that a beneficial hypertrophic phenotype exists. In search of an underlying molecular substrate we used microarray technology to identify cardiac gene expression in response to exercise. Rats exercised for seven weeks on a treadmill were characterized by invasive blood pressure measurements and echocardiography. RNA was isolated from the left ventricle and analysed on DNA microarrays containing 8740 genes. Selected genes were analysed by quantitative PCR. The exercise program resulted in cardiac hypertrophy without impaired cardiac function. Principal component analysis identified an exercise-induced change in gene expression that was distinct from the program observed in maladaptive hypertrophy. Statistical analysis identified 267 upregulated genes and 62 downregulated genes in response to exercise. Expression changes in genes encoding extracellular matrix proteins, cytoskeletal elements, signalling factors and ribosomal proteins mimicked changes previously described in maladaptive hypertrophy. Our most striking observation was that expression changes of genes involved in beta-oxidation of fatty acids and glucose metabolism differentiate adaptive from maladaptive hypertrophy. Direct comparison to maladaptive hypertrophy was enabled by quantitative PCR of key metabolic enzymes including uncoupling protein 2 (UCP2) and fatty acid translocase (CD36). DNA microarray analysis of gene expression changes in exercise-induced cardiac hypertrophy suggests that a set of genes involved in fatty acid and glucose metabolism could be fundamental to the beneficial phenotype of exercise-induced hypertrophy, as these changes are absent or reversed in maladaptive hypertrophy.

Validating the EQ-5D with time trade off for the German population.

The aim of this survey study was to derive the societal values of the general public for the EuroQol EQ-5D. Using the same protocol as previously used in the United Kingdom, we compared the German values with the British. In face-to-face interviews a sample of 339 individuals in northern Germany valued 15 different health states from a sample of 36 states. Values were derived using the York MVH protocol for time trade-off (TTO) and a visual analogue scale (VAS). Values for all 243 health states of the EQ-5D were estimated by a regression model. The VAS values revealed close a resemblance to the British VAS results. German TTO values were higher than the British. This was especially the case for the worse health states. The results suggest that the TTO values are more related to national variables than values derived by VAS. The use of the TTO values of this investigation makes it possible to anticipate these cultural differences in studies carried out in Germany.

Involvement of cyclin D activity in left ventricle hypertrophy in vivo and in vitro.

OBJECTIVE: Cardiac hypertrophy is induced by a number of stimuli and can lead to cardiomyopathy and heart failure. Present knowledge suggests that cell-cycle regulatory proteins take part in hypertrophy. We have investigated if the D-type cyclins are involved in cardiac hypertrophy. METHODS: The expression and activity of the D-type cyclins and associated kinases in cardiomyocytes were studied during angiotensin II- and pressure overload-induced hypertrophy in rats (Rattus norvegicus) and in isolated, neonatal cardiomyocytes. Expression of the D-type cyclins was manipulated pharmacologically and genetically in neonatal myocytes. RESULTS: In the left ventricle, there was a low, constitutive expression of the D-type cyclins, which may have a biological role in normal, adult myocytes. The protein level and the associated kinase activity of the D-type cyclins were up-regulated during hypertrophic growth. The increase in cyclin D expression could be mimicked in vitro in neonatal cardiac myocytes. Interestingly, the cyclin Ds were up-regulated by hypertrophic elicitors that stimulate different signalling pathways, suggesting that cyclin D expression is an inherent part of cardiac hypertrophy. Treatment of myocytes with the compound differentiation inducing factor 1 inhibited expression of the D-type cyclins and impaired hypertrophic growth induced by angiotensin II, phenylephrine and serum. The response to hypertrophic elicitors could be restored in differentiation inducing factor 1-treated myocytes by expressing cyclin D2 from a heterologous promoter. CONCLUSION: Our results point to the D-type cyclins as important regulators of cardiac hypertrophy. This supports the notion that cell-cycle regulatory proteins regulate hypertrophic growth.

Direct costs for the treatment of HIV-infection in a German cohort after the introduction of HAART.

BACKGROUND: Highly active antiretroviral combination therapy (HAART) has become the standard of care for HIV infection. The reduction of morbidity by HAART has been proven to be cost-effective despite high expenditures for regular use of antiretrovirals. We examined direct costs in a German monocentric cohort of HIV-infected patients after introduction of HAART. SUBJECTS/METHODS: In 1997 recruitment started and 201 patients gave informed consent. They underwent structurized interviews. Additional data were taken from the patients records. Later on follow-ups were performed for the same cohort in the years 2000 and 2001 respectively. Direct costs have been calculated per patient and year for each period. RESULTS: The proportion of HAART treated patients rised in the cohort from 86% to 93%. The mean of antiretrovirals used per case increased from 2.4 to 3.4. Nevertheless mean direct costs for HAART decreased significantly from Euro 17,746 to Euro 16,007. Reduction of expenditures for additional drugs, hospitalisation and diagnostics led to about one third decrease of mean total direct cost from Euro 35,865 in 1997 to Euro 24,482 in 2001. For surviving patients expenditures remained higher in advanced stage of disease for HAART, hospitalisation, diagnostics and total costs. CONCLUSION: Expenditures for HAART remained on a high level. Despite rising drug prices and increased use of antiretrovirals a decrease of mean costs of HAART by about 10% resulted from more frequent use of less expensive drug combinations. The continuous decrease of expenditures for non-HAART drugs, diagnostics and hospitalisation predominated and therefore HAART caused about a half of total direct costs in 1997 and two third in 2001 respectively. Higher expenditures in advanced stages of disease continued over the follow up period and raise the question of an economic impact of earlier initiation of treatment. More extensive use of standardized evaluation of direct costs could be an important tool towards a more rational allocation of resources in health care.

Treatment costs and quality of life of patients with peripheral arterial occlusive disease--the German perspective.

BACKGROUND: To objectify the debate about the restricted resources of the health system, examinations about the treatment costs and quality of life implications of different illnesses are necessary. The aims of the examination were the quantification of costs that are caused by a patient with PAD per year and the determination of the quality of life. PATIENTS AND METHODS: 280 patients (mean 66.6 years) in Fontaine stages II to IV were included in the study to determine their treatment costs for the year 2001 retrospectively from patient records. Health-related quality of life was recorded through the standardized questionnaires PAVK-86, SF-36 and EQ-5D. RESULTS: A patient with PAD in stage Ila costs on average 1792.45 Euros, in stage IIb 2551.28 Euros, in stage III 4356.48 Euros and in stage IV 6225.89 Euros. The costs of the in-hospital treatment dominated the total result on average with 44.4% of the direct costs. Further cost factors were the drugs with 33.4%, the out-patient medical treatment with 9.9%, the expenditures for care with 6.7%, rehabilitation with 3.6% and adjuvants with a share of 1.9%. The indirect costs played a subordinate role with 9.67% of the total costs. The quality of life was clearly restricted in all stages of the PAD. The quality of life especially was strongly decreased from the Fontaine stage IIb on. The problems were mainly in the areas of the physicalfunctions and pain. CONCLUSION: The study showed that the treatment of patients with PAD is very cost-intensive and that patients have to suffer from a considerable loss of quality of life.

The use of perfluorocarbon liquids in vitreous surgery.

Perfluoro-octane is used as an intraoperative tool for manipulation of the retina during vitreous surgery for retinal detachment in cases of proliferative vitreoretinopathy (PVR), giant tears and large peripheral retinotomies. One case of a macular hole combined with a peripheral one was also treated in this way. Perfluoro-octane seems, in our experience, a useful instrument for intraoperative atraumatic flattening of the retinal in those complicated cases with largely detached retinas.

Treatment of complicated retinal detachment with proliferative vitreoretinopathy.

A short history of vitrectomy and its complications is presented. The surgical procedure for treatment of RD complicated by PVR is described. Finally the indications for the use of silicone oil during surgery are discussed together with its complications.

Subretinal hemorrhage removal.

Subretinal hemorrhages can be caused by different pathologies. In our opinion the subretinal neovascularizations associated with age related macular degeneration are the most frequent cause of these subretinal hemorrhages. The surgical indications of this pathology are presented and illustrated by 10 cases we operated on over the last two years. The surgical technique and the prognosis of the treatment are discussed.

Treatment of posterior eye segment complications after perforating trauma.

168 perforating trauma cases that underwent vitreoretinal surgery in our hospital over a two year period were reviewed. A uniform surgical concept was applied in those severely injured eyes. Showing posterior eye segment complications that required vitreoretinal surgery and having at least light perception were the only two criteria to be eligible for this study. The anatomic and functional results in different trauma groups are discussed as well as indications and duration of silicone oil tamponade.

Efficacy of tissue plasminogen activator (t-PA) in subretinal hemorrhage removal.

t-PA can be used intra-operatively to liquify a large and elevated submacular blood clot and to facilitate the aspiration through a small retinotomy. In 15 consecutive patients we operated in this way, we noticed that an intra-operative subretinal injection of t-PA was never able to dissolve the blood clot completely. Therefore it was necessary to perform a large retinotomy in large hemorrhages.

Silicone oil vs. gas for the treatment of full-thickness macular hole.

The purpose of this study is to evaluate the anatomic and visual outcomes, as well as the complications, of macular hole surgery with SF6-gas tamponade versus silicone-oil tamponade. Fifty-four (54) eyes with idiopathic macular hole underwent vitrectomy and peeling of the internal limiting membrane (ILM) around the hole. Nineteen (19) eyes were treated with SF6-gas tamponade (group 1) and the other thirty-five (35) eyes with silicone-oil tamponade (group 2). An excellent anatomic success rate was obtained in both groups (94.7% in group 1 and 97.1% in group 2). Nevertheless, the postoperative visual acuity (VA) in the group treated with silicone-oil tamponade was significantly better than in the group treated with gas tamponade (P = 0.0217). Forty-seven (47) of the eyes in group 1 and 74% in group 2 achieved a VA = 0.4 or better. The most frequent potentially vision threatening complication we observed was RPE alterations in 35% of the eyes in group 1 and in only one eye in group 2. None of the eyes developed a retinal detachment during the follow-up period. In conclusion, the treatment of idiopathic macular holes by vitrectomy and ILM peeling provides a very good anatomic success rate. An excellent recovery of visual acuity, up to 1.0, was more frequently observed in the group treated with silicone oil tamponade.