Digitally Analyzed Conjunctival Redness: Does Repeated Conjunctival Provocation Intrinsically Cause Local Desensitization of the Eye?

Background: Allergic reactions in patients with seasonal or perennial rhinoconjunctivitis mediated by airborne allergens can be effectively assessed with the conjunctival provocation test (CPT). The CPT is a fast and easy diagnostic procedure that challenges the ocular mucosa with instillations of allergen solutions into the conjunctival region. This paper aimed to investigate the possible influence of repeated diagnostic CPT procedures on the patient's clinical presentation, i.e. to analyze desensitization effects caused by diagnostic solutions and to show the reproducibility of CPT results. Methods: Treatment progress in 120 placebo-treated patients from 2 immunotherapeutic dose-finding studies was estimated and documented, as based on the CPT which was applied at 4 visits with intervals of 4, 8 and 16 weeks. High-resolution digital photos collected as part of the CPT documentation were analyzed by an external observer and by digital analysis software to determine conjunctival redness, completely independent of the subjectivity of investigators and patients. Results: Two extremal scenarios of the redness changes were considered after provocation with 10,000 standard quality units/ml. A maximal decrease of about 3% (t test: p = 0.0002; U test: p = 0.001) and a minimal decrease of about 1% (t test: p = 0.254; U test: p = 0.431) were found. Conclusions: The observed decrease in conjunctival hyperemia can be explained by local desensitization or by placebo effect. Due to the setup of both studies considered, we could not ascertain how these factors influence the decrease in redness. In order to attribute the observed effects to local conjunctival desensitization with certainty, further pilot studies are needed. (C) 2016 S. Karger AG, Base

Automatic conjunctival provocation test using Hough transform of extended canny edge maps

Computer-aided diagnosis is developed for assessment of allergic rhinitis/rhinoconjunctivitis measuring the relative redness of sclera under application of allergen solution. The patient’s eye images are taken from commercial digital camera. The iris is robustly localized using a gradient-based Hough circle transform. From the center of the pupil, the region of interest within the sclera is extracted using geometric anatomybased a-priori information. The red color pixels are extracted thresholding in the hue, saturation and value color space. Then, redness is measured by taking mean of saturation projected into zero hue. Evaluation is performed with 92 images taken from 13 subjects, 8 responders and 5 non-responders, which were classified according to an experienced otorhinolaryngologist. Provocation is performed with 100, 1,000 and 10,000 AU/ml allergic solution and normalized to control images without provocation. The evaluation yields redness of 1.14, 1.30, 1.60 and 1.04, 1.12, 1.11 for responders and non-responders, respectively. This indicates that our method is suitable as reliable endpoint in controlled clinical trials

Reliability of a New Symptom Score in a Titrated Quantitative Conjunctival Provocation Test Supported by an Objective Photodocumentation

Background: Allergen provocation tests are useful methods for proving the clinical relevance of an allergen-specific sensitization. Among these methods, the conjunctival provocation test (CPT) represents an easy-to-use tool. However, its readout parameters have not yet been internationally standardized or validated. Photodocumentation has been shown as a good option for objectifying a CPT reaction, supporting the local investigator assessment. Based on test-retest reliability of the score and an objective digital photoanalysis of the conjunctival redness, this study aimed to prove the reproducibility of a new CPT scoring system for use in clinical trials (ClinicalTrials. gov identifier: NCT02690740). Methods: A titrated quantitative CPT was conducted outside of the pollen season in a final cohort of 23 adult patients with birch or grass pollen-induced allergic rhinoconjunctivitis. Conjunctival symptoms were analyzed using a standardized symptom score. Conjunctival redness was also evaluated by an external observer and correlated with a digital photoanalysis using MATLAB software. Results: A test-retest correlation of 0.6 (p < 0.01) was found for the symptom score results. Likewise, a correlation of 0.65 (p < 0.01) was observed in the digital photoanalysis. The total symptom score showed a decrease in the mean value of 0.48 score points in the retest. Conclusions: This study reveals both a valuable test-retest correlation of the proposed score as well as a good correlation of eye redness with the (objective) photodocumentation. Based on our results, we can recommend the use of this scoring system as a valuable clinical protocol for future clinical trials. (C) 2018 S. Karger AG, Base

High performance liquid chromatography fluorescence detection method for endogenous gamma aminobutyric acid validated by mass spectrometric and gas chromatographic techniques

Endogenous y-aminobutyric acld (GABA) from aqueous (1 M KCI/HCI) or organic (methanol) homogenates of rat brain tissue has been determined by reversed-phase isocratic high-performance liquid chromatography (HPLC) (0.1 M H,PO,/acetonitrile, 4:6 at pH 2.8) with fluorometric detection of the corresponding o-phthalaidehyde derivative at 360 nm (excitation) and 440 nm (emission). Calibration standards were prepared with deuteriated GABA and/or aminovaleric acid (AVA). The precision of the method was 3.2% and the detection limit was established at 64 pg of GABA on column allowing the determination of GABA at the level of 1.7 ng/mg of tissue. The content of GABA In brain was 227.2 f 11.1 ( n = 10) pg/g and in cerebellum 110.3 f 13.9 ( n = 10) pg/g. Average recovery was 91.4 f 11.6%. The method was validated by comparison of these results with those obtained by analyzing brain homogenates of 10 rats by capillary gas chromatography-mass spectrometry, direct thermospray high-performance liquid chromatography-mass spectrometry, and gas chromatography with electron capture detection.Peer reviewe

Liposomal Eye Spray Is as Effective as Antihistamine Eye Drops in Patients with Allergic Rhinoconjunctivitis Induced by Conjunctival Provocation Testing

Background: Liposomal eye spray (LS) has been introduced for the treatment of dry eye. Whether LS can also relieve symptoms due to allergic rhinoconjunctivitis (ARC) has not yet been sufficiently investigated. Objectives: The aim of this study was to assess the onset of action, the reduction of allergy symptoms, and the safety of LS - a nonpharmacological treatment option - compared with those of antihistamine eye drops (AD). Methods: In this open, prospective, controlled, monocenter noninterventional study, adults with ARC received either LS or AD for the relief of eye irritation after a positive conjunctival provocation test (CPT). All patients completed a questionnaire before and after the CPT. Eye irritation was rated on a visual analogue scale (VAS) at 6 time points. Conjunctival redness was analyzed using objective digital analysis based on images taken during the study visit. Results: Data were collected from 40 patients (20 per group). In both groups, 80% of patients perceived an onset of action within 0-2 min after application of LS or AD following the CPT. Relief of eye irritation (as determined by VAS) increased throughout the visit for both groups. In the digital analysis, the mean proportion of redness of the eye decreased from 10.3 to 7.0% for LS and from 10.4 to 6.5% for AD, with the largest difference observed 10 min after application (LS: 8.9%; AD: 6.0%; p = 0.094). Conclusions: LS is a nonpharmacological treatment option for ARC, showing no significant difference or relevant numerical inferiority to AD in any parameter studied. It was generally safe and well tolerated. (C) 2019 S. Karger AG, Base

Noise patterns in visceral surgical procedures: Analysis of second-bysecond dBA data of 599 procedures over the course of one year

The objective of this study is to analyze noise patterns during 599 visceral surgical procedures. Considering work-safety regulations, we will identify immanent noise patterns during major visceral surgeries. Increased levels of noise are known to have negative health impacts. Based on a very finegrained data collection over a year, this study will introduce a new procedure for visual representation of intra-surgery noise progression and pave new paths for future research on noise reduction in visceral surgery. Digital decibel sound-level meters were used to record the total noise in three operating theatres in one-second cycles over a year. These data were matched to archival data on surgery characteristics. Because surgeries inherently vary in length, we developed a new procedure to normalize surgery times to run cross-surgery comparisons. Based on this procedure, dBA values were adjusted to each normalized time point. Noise-level patterns are presented for surgeries contingent on important surgery characteristics: 16 different surgery types, operation method, day/night time point and operation complexity (complexity levels 1–3). This serves to cover a wide spectrum of day-to-day surgeries. The noise patterns reveal significant sound level differences of about 1 dBA, with the mostcommon noise level being spread between 55 and 60 dBA. This indicates a sound situation in many of the surgeries studied likely to cause stress in patients and staff. Absolute and relative risks of meeting or exceeding 60 dBA differ considerably across operation types. In conclusion, the study reveals that maximum noise levels of 55 dBA are frequently exceeded during visceral surgical procedures. Especially complex surgeries show, on average, a higher noise exposure. Our findings warrant active noise management for visceral surgery to reduce potential negative impacts of noise on surgical performance and outcome

Subcutaneous immunotherapy with depigmented-polymerized allergen extracts: a systematic review and meta-analysis

BackgroundDouble-blind, placebo-controlled trials (DBPCTs) have confirmed the efficacy of allergen-specific immunotherapy (AIT) with depigmented-polymerized allergen extracts (DPAEs). This systematic review evaluates the efficacy of AIT using different allergens in different severity stages of rhinoconjunctivitis with or without asthma in the pollen studies and asthma and rhinitis in the house dust mite studies in comparison to placebo.MethodsWe used MEDLINE, Embase, CENTRAL and LILACS databases to review DBPCTs published until July 2016. The combined symptom and medication score (cSMS) served as primary endpoint. The total rhinoconjunctivitis symptom score (RCSS) and total score in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were secondary efficacy endpoints. Solicited local and systemic adverse events were secondary safety endpoints. We assumed a random effects model with standardized mean differences (SMDs) or mean differences as summary statistics. In a subgroup analysis, we classified the studies following the GINA (Global Initiative for Asthma) and ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines for rhinoconjunctivitis and asthma severity.ResultsSix DBPCTs in pollen and 2 trials in house dust mites (HDM) were selected. Patients (N=915) with intermittent or mild persistent asthma were included in 3 (37.5%) and 5 (62.5%) trials, respectively. Two (25%) HDM studies included patients with moderate persistent asthma, 4 trials patients with moderate-to-severe rhinoconjunctivitis. Treatment periods ranged from 12 to 24months. AIT with DPAEs yielded significantly lower cSMS (SMD: 1.9, 95% CI: 0.9-2.8) and RQLQ (SMD: 0.3, 95% CI: 0.1-0.5) values than did placebo. An exploratory analysis of cSMS and RCSS suggested that the efficacy of AIT treatment with DPAEs was higher in trials including patients with more severe rhinoconjunctivitis and asthma. A publication bias was not detected. Heterogeneity between individual studies was explained by differences in severity. Patients receiving DPAEs did not experience a significantly higher risk of local (OR: 1.55, 95% CI: 0.86-2.79) or systemic reactions (OR: 1.94, 95% CI: 0.98-3.84).ConclusionsCompared to placebo, AIT with DPAEs is effective in patients with pollen- or HDM-induced rhinoconjunctivitis with or without allergic asthma and improves health-related quality of life. It does not differ significantly in safety and tolerability

The H1 very forward proton spectrometer at HERA

The very forward proton spectrometer, VFPS, is a component of the H1 detector at the HERA collider. Scattered protons emitted with a polar angle less than 1 mrad and carrying a fractional energy 1-xP, 0.008<xP≤0.028 of the incident proton beam energy can be detected by scintillating fiber detectors which are read out by position sensitive photo-multipliers. These detectors are contained in Roman pot stations which are moved close to the circulating proton beam. The structure, operation and performance of the two Roman pot stations located at about 220 m from the H1 interaction point in the cryogenic section of the proton ring are described. © 2013 Elsevier B.V.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Early nonreactivity in the conjunctival provocation test predicts beneficial outcome of sublingual immunotherapy

Abstract Background Clinical practice needs a common parameter that can provide an early, reliable estimation of the outcome of sublingual immunotherapy (SLIT) in an upcoming pollen season. We investigated whether the conjunctival provocation test (CPT) can predict the beneficial outcome of SLIT in patients with allergic rhinoconjunctivitis after 4 weeks of treatment. Methods We conducted two separate prospective, randomized, double-blind, placebo-controlled, multicenter trials. Adults 18–75 years of age received placebo or SLIT tablets containing tree or grass pollen allergoids and underwent CPTs. Participants receiving SLIT were divided into two groups (reactive, nonreactive) according to their CPT reactions after 4 weeks of treatment. These two groups were compared with regard to clinical outcome parameters (total combined score, rhinoconjunctivitis total symptom score, total rescue medication score, well days) assessed during the pollen season for the 14-day (tree) or 30-day (tree/grass) peaks and for the entire 60-day seasons. Participants’ global evaluations of therapy after completing treatment were also compared. Results The tree pollen trial randomized 188 participants; 182 participants were evaluable, 76 of whom received SLIT and were suitable for this post hoc analysis. The grass pollen trial included 90 participants; 82 participants were evaluable, 44 of whom underwent SLIT. Comparing SLIT participants who reacted to the CPT after 4 weeks (tree: 77.6%; grass: 79.5%) with those who ceased to show a reaction (tree: 22.4%; grass: 20.5%) (tree: P = 0.0001; grass: P = 0.003), the total combined score for the 14-day (P = 0.017) and 30-day peaks (P = 0.042) as well as the rhinoconjunctivitis total symptom score assessed for the 14-day peak (P = 0.024) were significantly lower in the nonreactive group of the tree pollen trial. In the grass pollen trial, the nonreactive group rated their SLIT treatment significantly better (P = 0.019). Conclusions Using clinically meaningful outcome parameters during the pollen season, both trials independently led to similar results when comparing participants’ reactions to the CPT 4 weeks after beginning SLIT. These results suggest that CPT allows an early estimation of allergic rhinoconjunctivitis symptoms before an upcoming season. Thus, the CPT can be used as a valuable parameter to predict the beneficial outcome of ongoing SLIT. Trial registration Both trials registered with the Medical Ethics Committee of the North Rhine Medical Council (EudraCT numbers 2012-004916-79 (grass pollen trial) and 2013-002129-43 (tree pollen trial)) and the German Federal Ministry of Health (Paul-Ehrlich-Institut)