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Background: A 3-week short-course of adjuvant-free hydrolysates of Lolium perenne peptide (LPP) immunotherapy for rhinoconjunctivitis with or without asthma over 4 physician visits is safe, well tolerated, and effective., Objective: We sought to investigate immunologic mechanisms of LPP immunotherapy in a subset of patients who participated in a phase III, multicenter, randomized, double-blind, placebo-controlled trial (clinical.govNCT02560948)., Methods: Participants were randomized to receive LPP (n = 21) or placebo (n = 11) for 3 weeks over 4 visits. Grass pollen-induced basophil, T-cell, and B-cell responses were evaluated before treatment (visit [V] 2), at the end of treatment (V6), and after the pollen season (V8)., Results: Combined symptom and rescue medication scores (CSMS) were lower during the peak pollen season (-35.1%, P = .03) and throughout the pollen season (-53.7%, P = .03) in the LPP-treated group compared with those in the placebo-treated group. Proportions of CD63 + and CD203c bright CRTH2 + basophils were decreased following LPP treatment at V6 (10 ng/mL, P < .0001) and V8 (10 ng/mL, P < .001) compared to V2. No change in the placebo-treated group was observed. Blunting of seasonal increases in levels of grass pollen-specific IgE was observed in LPP-treated but not placebo-treated group. LPP immunotherapy, but not placebo, was associated with a reduction in proportions of IL-4 + T H 2 (V6, P = .02), IL-4 + (V6, P = .003; V8, P = .004), and IL-21 + (V6, P = .003; V8, P = .002) follicular helper T cells. Induction of FoxP3 + , follicular regulatory T, and IL-10 + regulatory B cells were observed at V6 (all P < .05) and V8 (all P < .05) in LPP-treated group. Induction of regulatory B cells was associated with allergen-neutralizing IgG 4 -blocking antibodies., Conclusion: For the first time, we demonstrate that the immunologic mechanisms of LPP immunotherapy are underscored by immune modulation in the T- and B-cell compartments, which is necessary for its effect., (Copyright © 2019. Published by Elsevier Inc.)

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence)., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol., Methods: In a prospective, dose-escalation study, 61 grass pollen-allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG 4 and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8)., Results: No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG 4 levels were higher at V6 (8.1-fold, P < .001) and V8 (12.2-fold, P < .001) than at V1. The sIgE:sIgG 4 ratio decreased at V6 (-54.6%, P < .001) and V8 (-71.6%, P < .001) compared to V1. The absolute decrease in IgE-facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8., Conclusion: Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies., (© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background: A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety., Methods: This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen-specific immunoglobulins were analysed before and after treatment., Results: Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per-protocol set). Also, 39% of patients in the 170-μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG 4 levels increased to 1.6-fold (70 μg), 3.1-fold (170 μg) and 3.9-fold (370 μg) (mPP)., Conclusion: Three-week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies., (© 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background: In recent decades, the incidences of anaesthesia-related perioperative mortality and adverse outcomes have decreased drastically. However, to date, data on perioperative cardiac arrest and risk factors of perioperative cardiac arrest from European countries are scarce., Objectives: To determine the incidences of perioperative cardiac arrest and rates of anaesthesia-related and anaesthesia-contributory cardiac arrest. Identification of pre-existing risk factors leading to perioperative cardiac arrest., Design: Retrospective cohort study., Setting: Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany., Interventions: Perioperative critical incident reports between 2007 and 2012 were screened, and reports on cardiac arrest within 24 h postoperatively were identified. Cardiac arrests were classified as 'anaesthesia-related', 'anaesthesia-contributory' or 'anaesthesia-unrelated' by two reviewers independently. Univariate and multi-variate logistic regression analysis was used to identify risk factors associated with perioperative cardiac arrest., Results: Analysis of 318 critical incidents from 169 500 anaesthetics revealed 99 perioperative cardiac arrests. This is an overall incidence of perioperative cardiac arrest of 5.8/10 000 anaesthetics [95% confidence interval (CI), 4.7 to 7.0]. The rate of anaesthesia-related cardiac arrest was 0.7/10 000 (95% CI, 0.3 to 1.1), and the rate of anaesthesia-contributory cardiac arrest was 1.7/10 000 (95% CI, 1.1 to 2.3). Most cardiac arrests related to anaesthesia were due to respiratory events. From the multi-variate analysis, American Society of Anesthesiologists physical status grade at least 3 [P = 0.007, odds ratio (OR) 2.59 (95% CI, 1.29 to 5.19)], emergency surgery [P < 0.001, OR 4.00 (95% CI, 2.15 to 7.54)] and pre-existing cardiomyopathy [P < 0.001, OR 17.48 (95% CI, 6.18 to 51.51)] emerged as predictors of cardiac arrest., Conclusion: These first available European data on perioperative cardiac arrest from a large unselected cohort indicate that the overall perioperative incidence of cardiac arrest at our institution was slightly lower than published in the literature, whereas rates of anaesthesia-related and anaesthesia-contributory cardiac arrest were comparable. Most cardiac arrests related to anaesthesia were due to respiratory events. American Society of Anesthesiologists physical status grade at least 3, emergency surgery and pre-existing cardiomyopathy appear to be relevant risk factors for cardiac arrest.

Background: A relevant proportion of allergic rhinoconjunctivitis (ARC) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, noninterventional study used internationally standardized instruments to determine the clinical effects of a preseasonal, ultra-short-course booster AIT on clinical outcome parameters., Methods: This two-arm study included patients aged ≥12 years with recurrent grass pollen-induced seasonal AR who had completed a successful course of any grass pollen AIT at least 5 years before enrolment. Overall, 56 patients received one preseasonal short-course booster AIT using tyrosine-absorbed grass pollen allergoids containing the adjuvant monophosphoryl lipid A (MPL ® ); 51 control patients received symptomatic medication. The combined symptom and medication score (CSMS) was recorded in the (peak) grass pollen season. Furthermore, concomitant (antiallergic) medication use, the patients' state of health, Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) results and safety/tolerability of the treatment were assessed., Results: The CSMS in the peak grass pollen season was significantly lower in the booster AIT group (Δ=38.4%, P<.01). Moreover, significantly more patients in this group used no concomitant antiallergic medication throughout the peak grass pollen season. Twice as many patients in the booster AIT group as in the control group reported having a better state of health than in the preceding season. MiniRQLQ results showed significant differences favouring the booster AIT. The booster AIT was generally well tolerated, with only two patients reporting mild, grade 1 systemic adverse events., Conclusion: Booster AIT using tyrosine-absorbed allergoids containing the adjuvant MPL ® effectively prevents re-occurrence of symptoms in patients with grass pollen-induced ARC., (© 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Purpose: Hyponatremia is a common electrolyte abnormality seen in hospitalized patients. It may cause a variety of symptoms and is associated with longer hospitalizations and higher mortality. However, to date, only little is known about the extent of hyponatremia in patients with incurable diseases and whether it is associated with physical symptoms in this patient group. This study aims to describe the prevalence of hyponatremia, associated symptoms, and symptom intensity in inpatients with hyponatremia receiving specialist palliative care (SPC)., Methods: This is a retrospective study. Demographic and clinical data as well as symptoms, scored symptom intensity, and laboratory values were collected. All inpatients of a large German University Hospital receiving SPC in 2013 with documented sodium values were included., Results: In 2013, 789 inpatients received SPC of which 710 had documented sodium values. The prevalence of hyponatremia was 38.7% (275/710). A mild degree showed 220 (31,0%), 44 (6.2%) had a moderate, and 11 (1.6%) a severe form. Hyponatremia patients experienced significantly more symptoms than normonatremic patients (mean = 7.71 vs 6.63; p < 0.001). Breathlessness, depressiveness, nausea, vomiting, poor appetite, constipation, and weakness were significantly more frequent in patients with hyponatremia. Furthermore, hyponatremia severity was associated with higher symptom intensity (mean = 13.29 vs 11.28; p < 0.001)., Conclusions: More than one third of all SPC patients showed a hyponatremia, and the hyponatremia grade was associated with symptom burden and symptom intensity. A prospective analysis is needed to further examine this association and the possible influence of hyponatremia correction on symptom burden reduction.

Background: To inform the development of the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT., Methods: We performed a systematic review, which involved searching nine databases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses., Results: 98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of -1.11 (95% CI -1.66, -0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD -1.21 (95% CI -1.87, -0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95% CI -0.23, 0.58), but one study showed a beneficial long-term effect. For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen-specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR. AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported. The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective., Conclusions: AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Previous reviews and meta-analyses demonstrated effects of cognitive interventions in dementia, but none specifically considered residents with dementia in long-term care (LTC) facilities., Objective: To analyse the efficacy of cognitive interventions in institutionalised individuals with dementia., Methods: After identifying 27 articles, a systematic review was performed. A meta-analysis was calculated for 15 studies of the randomized controlled trials regarding effects on relevant outcomes. Fixed-effects meta-analyses were conducted using standardized mean differences (SMD) of changes from baseline pooled using the inverse variance method., Results: When comparing cognitive interventions to passive control groups, the meta-analysis revealed significant moderate effects on global cognition (SMD=0.47, 95% CI 0.27-0.67), autobiographical memory (0.67, 0.02-1.31), and behavioral and psychological symptoms in dementia (BPSD; 0.71, 0.06-1.36). Significant small effects were detected for quality of life (QoL; 0.37, 0.05-0.70). Moderate effects on activities of daily living (0.28; -0.02 to 0.58) failed to reach significance; no effects were found on depression (0.22; -0.08 to 0.51). Significant moderate effects of global cognition (0.55; 0.22-0.89) and depression (0.64; 0.21-1.07) were also found for cognitive interventions contrasting active control groups. No harmful events related to the participation in the interventions were observed., Conclusion: Cognitive interventions are safe and effective for residents with dementia in LTC. However, while it seems clear that cognitive benefits can specifially be assigned to these forms of intervention, further research is necessary to clarify whether the effects on BPSD and QoL reflect unspecific changes due to additional attention. Furthermore, future studies will have to determine which intervention type yields the largest benefits., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies., Objective: We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients., Design: A prospective randomized, single-blinded, controlled study., Setting: Single-center, University Hospital of Aachen, Germany between July 2013-October 2015., Patients: Forty-six patients with regular renal function undergoing partial nephrectomy., Interventions: Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia., Main Outcome Measures: Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months., Results: Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months., Conclusion: Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon., Trial Registration: ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

Background: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities., Methods: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation., Results: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues., Conclusion: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited., Objectives: To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness., Methods: Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees., Results: Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group., Conclusion: The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial., (Copyright © 2016. Published by Elsevier Inc.)

Introduction: The external chest compression is a very important skill required to maintain a minimum of circulation during cardiac arrest until further medical procedures can be taken. Peyton's 4-Steps-Approach is one method of skill training, the four steps being: Demonstration, Deconstruction, Comprehension and Execution. Based on CPR skill training, this method is widely, allegedly predominantly used, although there are insufficient studies on Peyton's 4-Steps-Approach for skill training in CPR in comparison with other methods of skill training. In our study, we compared the medium- term effects on learning external chest compression with a CPR training device in three different groups: PEY (Peyton's 4-Steps-Approach), PMOD (Peyton's 4-Steps-Approach without Step 3) and STDM, the standard model, according to the widely spread method "see one, do one" (this is equal to Peyton's step 1 and 3)., Material and Methods: This prospective and randomised pilot study took place during the summer semester of 2009 at the SkillsLab and Simulation Centre of the University of Cologne (Kölner interprofessionelles Skills Lab und Simulationszentrum - KISS). The subjects were medical students (2(nd) and 3(rd) semester). They volunteered for the study and were randomised in three parallel groups, each receiving one of the teaching methods mentioned above. One week and 5/6 months after the intervention, an objective, structured single assessment was taken. Compression rate, compression depth, correct compressions, and the sum of correct checklist items were recorded. Additionally, we compared cumulative percentages between the groups based on the correct implementation of the resuscitation guidelines during that time., Results: The examined sample consisted of 134 subjects (68% female; age 22±4; PEY: n=62; PMOD: n=31; STDM: n=41). There was no difference between the groups concerning age, gender, pre-existing experience in CPR or time of last CPR course. The only significant difference between the groups was the mean compression rate (bpm): Group 1 (PEY) with 99±17 bpm, Group 2 (PMOD) with 101±16 bpm and Group 3 (STDM) with 90±16 bpm (p=0,007 for Group 3 vs. Group 1 and Group 3 vs. Group 2, Mann-Whitney- U-Test). We observed no significant differences between the groups after the second assessment., Conclusion: Our study showed that there are no essential differences in external chest compression during CPR performed by medical students dependent on the teaching method (Peyton vs. "Non-Peyton") implemented with regard to the medium-term effects. The absence of benefits could possibly be due to the simplicity of external chest compression.

Background: Medication reviews are recognized services to increase quality of therapy and reduce medication risks. The selection of eligible patients with potential to receive a major benefit is based on assumptions rather than on factual data. Acceptance of interprofessional collaboration is crucial to increase the quality of medication therapy., Objective: The research question was to identify and prioritize eligible patients for a medication review and to provide evidence-based criteria for patient selection. Acceptance of the prescribing general practitioner to implement pharmaceutical recommendations was measured and factors influencing physicians' acceptance were explored to obtain an impression on the extent of collaboration in medication review in an ambulatory care setting., Methods: Based on data of a cluster-randomized controlled study (WestGem-study), the correlation between patient parameters and the individual performance in a medication review was calculated in a multiple logistic regression model. Physician's acceptance of the suggested intervention was assessed using feedback forms. Influential factors were analyzed., Results: The number of drugs in use (p = 0.001), discrepancies between prescribed and used medicines (p = 0.014), the baseline Medication Appropriateness Index score (p<0.001) and the duration of the intervention (p = 0.006) could be identified as influential factors for a major benefit from a medication review, whereas morbidity (p>0.05) and a low kidney function (p>0.05) do not predetermine the outcome. Longitudinal patient care with repeated reviews showed higher interprofessional acceptance and superior patient benefit. A total of 54.9% of the recommendations in a medication review on drug therapy were accepted for implementation., Conclusions: The number of drugs in use and medication reconciliation could be a first rational step in patient selection for a medication review. Most elderly, multimorbid patients with polymedication experience a similar chance of receiving a benefit from a medication review. Longitudinal patient care should be preferred over confined medication reviews. The acceptance of medication reviews by physicians supports further implementation into health care systems., Trial Registration: ISRCTN ISRCTN41595373.

Background: The implementation of a computerized physician order entry (CPOE) can help reduce prescription errors in clinical practice., Objective: The aim of this study was to evaluate the effects of a CPOE for geriatric patients with the two most common conditions for drug-induced iatrogenic diseases, dysphagia and renal failure., Subjects and Methods: A retrospective analysis of actual drug prescriptions versus CPOE recommendations in the geriatric department of the St. Marien Hospital in Cologne, Germany was carried out. Actual drug prescriptions were collected for 26 patients with dysphagia (15 female, 11 male, average age 82.3 ± 8.0 years) and 35 patients with renal failure (23 female, 12 male, average age 80.5 ± 6.7 years) which were compared with recommended prescriptions by means of a CPOE and discrepancies were statistically analyzed., Results: Prescription errors for at least 1 drug were detected in 46 % of patients with renal failure and the administration of at least 1 drug with inadequate crushing was observed in 77 % of dysphagia patients., Conclusion: Prescription errors appear to be frequent to highly frequent in the medical routine even in a highly specialized geriatric setting. Inaccuracies might be reduced by the implementation of a CPOE and even more if coupled to a decision support system. Drug-drug or drug-disease interactions, which are particularly high risks in patients with multimorbidities, multidrug therapy, renal failure or malnutrition, might be kept under control through careful verification of medication indications, organ function status as well as drug administration and preparation in cases of tube feeding.

Purpose: Scleral buckling is currently used in addition to vitrectomy for the treatment of pseudophakic retinal detachment (PRD) to better support the vitreous base and better visualisation of the periphery., Aims: The aims of this study are to evaluate (1) whether the combination of 20 G vitrectomy and scleral buckling is superior to 20 G vitrectomy alone (control) (confirmatory), and (2) whether transconjunctival 23/25 G vitrectomy is non-inferior to 20 G vitrectomy (both without scleral buckling) regarding operation success (exploratory)., Methods: The VIPER (Vitrectomy Plus Encircling Band Vs. Vitrectomy Alone For The Treatment Of Pseudophakic Retinal Detachment) study is an unmasked, multi-centre, three-arm randomised trial. Patients with PRD were eligible, excluding complicated retinal detachment or otherwise severe ophthalmologic impairment. Patients were randomised to one of three interventions: 20 G vitrectomy alone (control C), combination of 20 G vitrectomy and circumferential scleral buckling (experimental treatment E1) or 23/25 G vitrectomy alone (experimental treatment E2). The primary endpoint is the absence of any indication for a retina re-attaching procedure during 6 months of follow-up. Secondary endpoints include best corrected visual acuity, retina re-attaching procedures, complications and adverse events., Results: From June 2011 to August 2013, 257 patients were enrolled in the study. The internet randomisation service assigned 100 patients each to the treatment arms C and E1, and 57 patients to treatment E2. The imbalance is due to the fact that several retinal surgeons did not qualify for performing E2. The random assignment was stratified and balanced (ie, 1:1 or 1:1:1 ratio) by surgeon., Conclusions: The described study represents a methodologically rigorous protocol evaluating the benefits of three different vitrectomy approaches to PRD. The projected results will help to establish their overall efficacy and will permit conclusions regarding their relative value., Trial Registration Number: DRKS00003158 (German Clinical Trials Register, DRKS)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Improvements in survival rates in pediatric oncology have resulted in a growing need to identify adverse effects and improve rehabilitation in this population., Objective: This cross-sectional study aimed to investigate active ankle dorsiflexion (DF) range of motion (ROM), gait, walking efficiency, and motor performance in a mixed childhood cancer survivor population in comparison to healthy peers., Methods: Active ankle DF-ROM (goniometer), gait (Microgate Optogait 2D Gait Analysis), walking efficiency (6-minute walk test), and motor performance (German Motor Test 6-18) were assessed in a mixed childhood cancer survivor population after cessation of medical treatment (n = 13) in comparison to healthy children matched for age and gender (n = 13)., Results: Active ankle DF-ROM, gait (stance, swing, and preswing phase), and walking efficiency were significantly impaired in survivors compared with control subjects. No significant difference between groups was found in motor performance., Conclusion: Despite sufficient total motor performance levels, specific limitations in physical functioning were identified in a mixed childhood cancer survivor sample. This highlights the importance of the present findings., Implication for Practice: The results from this study highlight the potential significance of limited ankle DF function, inhibited gait, and reduced walking efficiency as adverse effects of various types of childhood cancer. It is hoped this enhanced recognition by pediatric cancer patients, parents, and exercise professionals will initiate specific supportive strategies and potentially prevent further limitations.

Background: Hippotherapy is a form of therapeutic riding which is used in the treatment of neurological and muscular disorders. Until now there has not been any high-quality randomised study that has proven its effectiveness., Objective: The aims of this study are to evaluate whether hippotherapy (as add-on to physiotherapy and/or pharmacotherapy) is superior to the standard treatment (physiotherapy and/or pharmacotherapy as prior to the study) in terms of balance function and other patient relevant outcomes in patients with multiple sclerosis., Methods: The MS-HIPPO study is a prospective, randomised, examiner-blinded, controlled multicentre study. Patients were randomised to one of two groups: 12 weeks of hippotherapy accompanied by physiotherapy and/or pharmacotherapy (intervention) or 12 weeks of physiotherapy and/or pharmacotherapy as prior to the study (control). The primary endpoint is the change in balance function, as measured by the Berg Balance Scale (BBS). The treatment comparison is evaluated using a covariance analysis with baseline BBS, centre, age, gender and EDSS as covariates. Secondary endpoints include fatigue, quality of life, pain intensity and spasticity., Results and Conclusions: The described study is the first randomised study evaluating the benefits of hippotherapy for patients with multiple sclerosis. In 5 national centres ten study physicians will screen potential participants. The expected results will help to improve the knowledge on non-pharmaceutical therapeutic options in this field.

Introduction: Allergic rhinitis (AR) has a major negative impact on patients' quality of life (QoL) and carries a high socio economic burden. This is particularly the case for patients who experience symptoms for extended periods of time (i.e. those with perennial (PAR) or persistent AR (PER), depending on the classification system used). This review covers available pharmacological advances and recent developments in the treatment of PAR or PER., Areas Covered: Pharmacological AR treatment is used to reduce symptom burden and help restore patients' normal daily routine. Traditionally, non-sedating antihistamines and intranasal corticosteroids (INS) were the two drug classes recommended for use first line. These, along with antileukotrienes, decongestants, mast cell stabilizers and anticholinergics, constituted the bulk of the AR treatment arsenal. MP-AzeFlu (Dymista®, Meda, Solna, Sweden) is the most recent addition to that arsenal. It is a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) delivered in a single spray and has surpassed available therapies in terms of symptom control and treatment response. Other relatively new treatments for PAR or PER include H3 antihistamines, toll-like receptor (TLR) agonists, cellulose powders and micro-emulsions, novel biomolecular formulations and omalizumab. Each of these new additions is reviewed here., Expert Opinion: A new AR drug class has recently been introduced (i.e. RO1AD58). Currently MP-AzeFlu is the only treatment option within this drug class. It can be estimated that combination treatments like MP-AzeFlu will become the mainstay of PAR and PER therapy since use will result in better compliance, improved efficacy over INS and a faster response together with good levels of tolerability. The challenge is to find other equally, or more effective, combination treatments, as has been the therapeutic standard in bronchial asthma for decades. The potential of biologics, as well as TLR-agonists and other new treatment options needs to be further evaluated.

Background: Health-related quality of life (HRQOL) has received more and more attention as an outcome in cancer therapy. In this exploratory study, we assessed the long-term HRQOL among 77 surgically treated patients with parotid gland cancer., Methods: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions (EORTC-QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (EORTC-QLQ-C30-H&N35) questionnaires were used in a cross-sectional design. The mean time-lag between initial diagnosis and completion of the questionnaire was 89.7 months., Results: The HRQOL significantly increased with the time-lag to surgery and decreased with the patients' age. Factors with clinically significant effects in several areas of long-term HRQOL (ie, more than 4 scores) were age, type of neck dissection, preoperative facial nerve palsy, and postoperative radiation therapy., Conclusion: In parotid gland cancer surgery, factors, such as sex, age, type of surgery, facial nerve palsy, and radiation therapy, seem to be associated with clinically meaningful differences in long-term HRQOL scores., (© 2015 Wiley Periodicals, Inc.)

Background: Exercise interventions in pediatric oncology are feasible and safe. However, scarce data are available with regard to the effectiveness of outpatient, group-based exercise interventions. As well, the potential role of exercise to improve motor performance has not been adequately explored despite being a meaningful outcome during childhood with important implications for physical activity behavior. No study has yet demonstrated significant changes in motor performance after an exercise intervention., Procedures: This explorative, prospective study was designed to evaluate the effects of a 6-month, group-based, therapeutic exercise program for a mixed childhood cancer population on motor performance, level of activity, and quality of life. After cessation of inpatient medical treatment, childhood cancer outpatients aged 4-17 years exercised once a week during a 6-month period (IG). Comparison groups included childhood cancer outpatients receiving care as usual (CG(1)), as well as healthy peers (matched to IG by age and gender) (CG(2))., Results: Overall motor performance, various motor dimensions, activity in sport clubs and school sports, as well as physical and emotional well-being were significantly reduced in the IG at baseline. Significant differences between the IG and CG(1) and/or CG(2) were identified in the change of overall motor performance, single motor dimensions, overall level of activity, and emotional well-being from baseline to post-intervention., Conclusions: The exercise intervention was beneficial in terms of motor performance, level of activity, and emotional well-being. As such, this study provides support for group-based exercise as a potential strategy to improve these outcomes after inpatient medical treatment., (© 2015 Wiley Periodicals, Inc.)

Objectives: To document the effectiveness and safety of sublingual allergen immunotherapy (SLIT) with a five-grass pollen tablet (Oralair ) and compare different treatment options in a broad, non-selected population of patients in a real-world clinical setting., Research Design and Methods: This was a 2 year, open, prospective, multicenter, single-arm, non-interventional study. Patients with a history of clinically relevant allergic symptoms caused by grass pollen, confirmed by skin prick testing, received treatment with the five-grass pollen tablet. Concomitant treatment with symptomatic medication and/or additional SLIT or subcutaneous immunotherapy (SCIT) was permitted. Twelve-month data are presented here. Effectiveness was assessed comparing a combined rhinoconjunctivitis (RC) score derived from the severity of rhinitis and conjunctivitis symptoms under treatment with retrospective data of the previous year., Results: A total of 1408 patients participated in the study, of whom 434 were children/adolescents and 962 polyallergic. Compared with the grass pollen season preceding five-grass pollen tablet treatment, a statistically significant reduction of 49.9% was achieved in RC score for the total population (p < 0.001), and an improvement in overall health was perceived by 90.9% of patients. The overall population of polyallergic patients derived similar benefits from treatment with the five-grass pollen tablet as monoallergic patients. The percentage reduction in RC score was larger in polyallergic patients taking no additional therapy (60.2%) than in those taking concomitant symptomatic medication (38.1%) or allergen immunotherapy (AIT) (50.8%). Within the last of these groups, RC score improved by 47.6% among patients receiving additional SCIT, versus 54.8% with additional SLIT. Adverse drug reactions, reported in 15.3% of study participants, were mostly local in nature and mild or moderate in intensity., Conclusions: After 1 year of treatment, polyallergic patients responded similarly to the five-grass pollen tablet as monoallergic patients. For polyallergic patients in whom additional treatment was needed, a second SLIT may be more beneficial than a SCIT or symptomatic co-medication.

Objective: The individual outcome after cochlear implantation in children with auditory synaptopathy/neuropathy (AS/AN) is difficult to predict. A tool for preoperative assessment would be helpful for counseling parents. This study evaluates the outcome after CI in children with AS/AN and with sensorineural hearing loss (SNHL), and correlates it with the preoperative ECochG results in order to find specific parameters of prognostic value., Design: The improvement of auditory behavior after CI was retrospectively assessed using the LittlEARS questionnaire and quantified in a score (LS). This score was correlated with the CAP/SP ratio in the preoperative ECochG. The score was further correlated with the patient's age six months following CI., Study Sample: Nine children with AS/AN were compared to nine children with SNHL., Results: Both groups showed a significant improvement in LS following CI. There was a significant positive correlation between the CAP/SP ratio and the improvement in LS in all children. The correlation between age and LS was significantly negative in the SNHL group and positive in the AS/AN group., Conclusion: All children with AS/AN and SNHL benefit to a similar extent from CI. The preoperatively assessed CAP/SP ratio has a prognostic value for the development of auditory behavior following CI.

Background: Episodic breathlessness is one form of refractory breathlessness. Better understanding of the symptom is necessary for effective management., Aim: The aim was to describe the characteristics of episodic breathlessness in patients with advanced chronic obstructive pulmonary disease or lung cancer., Design: This is a longitudinal cohort study. Outcomes were assessed monthly by up to 13 telephone interviews: peak severity (modified Borg scale: 0-10), duration, frequency, and timing of breathlessness episodes. Data from each episode were pooled and analyzed using descriptive statistics. Associations between outcomes were explored by correlation coefficients., Setting/participants: Patients with chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease classification stage III or IV) or primary lung cancer (any stage) were recruited in two inpatient units (internal medicine) and two outpatient clinics in Oldenburg, Germany., Results: A total of 82 patients (50 chronic obstructive pulmonary disease, 32 lung cancer), mean age (standard deviation) 67 years (8 years) and 36% female, were included reporting on 592 breathlessness episodes (chronic obstructive pulmonary disease: 403, lung cancer: 189). Peak severity was perceived significantly higher in chronic obstructive pulmonary disease patients than in lung cancer patients (mean (standard deviation) Borg scale: 6.2 (2.1) vs 4.2 (1.9); p < 0.001). Episodes described by chronic obstructive pulmonary disease patients were longer than those described by lung cancer patients (median (range): 7 min (0-600) vs 5 min (0.3-120), p = 0.002)). Frequency was similar and most often daily in both groups. Severity and frequency of episodes were correlated in lung cancer patients (r = 0.324, p = 0.009)., Conclusion: Most breathlessness episodes are short (minutes) and severe with significant differences between chronic obstructive pulmonary disease and lung cancer patients. Effective management strategies are warranted to improve symptom relief and coping., (© The Author(s) 2015.)

Introduction: The early diagnosis of AS/AN in children remains challenging because it exclusively relies on the detection of OAE and/or CM, while ABR are pathologically changed or missing. The aim of our study was to ensure the diagnosis of AS/AN, demarcate it to an outer hair cell damage and possibly differentiate between pre- and postsynaptic pathologies., Methods: We retrospectively evaluated the transtympanic ECochG results of ten children with AS/AN and compared them to a matched group with SNHL and without any signs of AS/AN. We analyzed the thresholds, latencies and - as a new parameter - the amplitude ratio between CAP and SP., Results: CM and SP thresholds were significantly lower than CAP thresholds in AS/AN patients and significantly lower than SP and CM thresholds in SNHL patients with comparable CAP thresholds. The CAP/SP ratio of amplitudes in SNHL children was more than three times (significantly) higher than in AS/AN children. The cutoff value was set at 1.0 in order to differentiate between both groups with a 80-90% sensitivity and specificity. It was not possible to differentiate between a pre- and postsynaptic type of AS/AN in our collective., Summary and Conclusion: The ECochG can add valuable information for a precise differential diagnosis of AS/AN, especially in babyhood. We identified the CAP/SP ratio as a new parameter for differentiation between AS/AN and SNHL. When the CAP/SP ratio falls below 1.0, patients can be diagnosed AS/AN with high specificity and sensitivity. Significantly smaller SPL are needed to evoke SP and CM in the AS/AN group, thus showing the preserved hair cell function., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Allergen exposure leads to allergen sensitization in susceptible individuals and this might influence allergic rhinitis (AR) phenotype expression. We investigated whether sensitization patterns vary in a country with subtropical and tropical regions and if sensitization patterns relate to AR phenotypes or age., Methods: In a national, cross-sectional study AR patients (2-70 y) seen by allergists underwent blinded skin prick testing with a panel of 18 allergens and completed a validated questionnaire on AR phenotypes., Results: 628 patients were recruited. The major sensitizing allergen was house dust mite (HDM) (56%), followed by Bermuda grass (26%), ash (24%), oak (23%) and mesquite (21%) pollen, cat (22%) and cockroach (21%). Patients living in the tropical region were almost exclusively sensitized to HDM (87%). In the central agricultural zones sensitization is primarily to grass and tree pollen. Nationwide, most study subjects had perennial (82.2%), intermittent (56.5%) and moderate-severe (84.7%) AR. Sensitization was not related to the intermittent-persistent AR classification or to AR severity; seasonal AR was associated with tree (p < 0.05) and grass pollen sensitization (p < 0.01). HDM sensitization was more frequent in children (0-11 y) and adolescents (12-17 y) (subtropical region: p < 0.0005; tropical region p < 0.05), but pollen sensitization becomes more important in the adult patients visiting allergists (Adults vs children + adolescents for tree pollen: p < 0.0001, weeds: p < 0.0005)., Conclusions: In a country with (sub)tropical climate zones SPT sensitization patterns varied according to climatological zones; they were different from those found in Europe, HDM sensitization far outweighing pollen allergies and Bermuda grass and Ash pollen being the main grass and tree allergens, respectively. Pollen sensitization was related to SAR, but no relation between sensitization and intermittent-persistent AR or AR severity could be detected. Sensitization patterns vary with age (child HDM, adult pollen). Clinical implications of our findings are dual: only a few allergens -some region specific- cover the majority of sensitizations in (sub)tropical climate zones. This is of major importance for allergen manufacturers and immunotherapy planning. Secondly, patient selection in clinical trials should be based on the intermittent-persistent and severity classifications, rather than on the seasonal-perennial AR subtypes, especially when conducted in (sub)tropical countries.

Background: Nucleoplasty, based on Coblation® technology, is a minimally invasive procedure used to decompress herniated discs. Reviews to date--exclusively systematic reviews--recommend nucleoplasty for treating chronic back pain, although with the restriction of limited to fair evidence. We therefore aimed to summarize and interpret our calculated results, where possible comprehensively and quantitatively, using statistical methods in the context of a meta-analysis supplementing a systematic review. In the process, the central question was to statistically determine whether, and to what extent, nucleoplasty can positively affect pain relief and functional mobility as well as lower the complication rate., Objective: Newly published studies made it possible to conduct a meta-analysis of the visual analog scale (VAS), a measuring instrument used to determine pain intensity, and the Oswestry Disability Index (ODI), a scale that reflects the degree of impairment in percent. In addition to having clearly sound evidence for analyzing VAS/NPS data, the present, newly compiled meta-analysis was able to summarize VAS and ODI data quantitatively and to calculate a total complication rate for the first time. It was thereby possible to make a first comparison between nucleoplasty and conservative therapy (including epidural steroid injection)., Study Design: This meta-analysis examined all study data published in clinical trials involving the nucleoplasty procedure for plasma disc decompression., Methods: A systematic search using the terms nucleoplasty and/or plasma disc decompression was conducted for literature listed in MEDLINE. Twenty-seven eligible studies (22 prospective trials and 5 retrospective trials) were included, and pooled analyses as well as various subgroup analyses (differentiation between cervical and lumbar disc herniations, comparisons with alternative treatments such as epidural steroid injection) were performed based on their data., Results: Pain decreased from a baseline VAS value of 7.27 to 2.12 (postop/first day), 2.50 (one week), 2.70 (2 weeks), 3.23 (one month), 2.66 (6 weeks), 2.84 (3 months), 3.06 (6 months), 3.03 (12 months), 1.54 (18 months), and 3.69 (24 months) after nucleoplasty. The ODI value (baseline: 58.95) dropped to 28.60 (one week), 29.00 (2 weeks), 23.21 (one month), 30.00 (6 weeks), 18.30 (3 months), 22.54 (6 months), 24.43 (12 months), 12.82 (18 months), and 36.98 (24 months). Compared to baseline, significant pain reduction and improvement in functional mobility after nucleoplasty were observed at every time point. Nucleoplasty showed a total complication rate of 1.5%, with the individual rates being 0.8% for cervical and 1.8% for lumbar nucleoplasty. Nucleoplasty was superior to conservative therapy at every time point and for all 3 included parameters, at some measurement time points even significantly., Conclusions: Nucleoplasty reduces pain in the long term and improves patients' functional mobility. It is an effective, low-complication, minimally invasive procedure used to treat disc herniations.

Background. Thermal water inhalations and irrigations have a long tradition in the treatment of airway diseases. Currently there exists no systematic review or meta-analysis on the effectiveness of thermal water treatment in upper respiratory tract diseases. Methods. A systematic search in the databases of MEDLINE, EMBASE, CENTRAL, ISI Web of Science, and MedPilot was accomplished. Results. Eight evaluable outcome parameters from 13 prospective clinical studies were identified for 840 patients. Mucociliary clearance time improves significantly (P < 0.01) for the pooled thermal water subgroup and the sulphurous subgroup after 2 weeks (-6.69/minutes) and after 90 days (-8.33/minutes), not for isotonic sodium chloride solution (ISCS). Nasal resistance improved significantly after 2 weeks (Radon, ISCS, and placebo), after 30 days (sulphur and ISCS), and after 90 days (sulphur). Nasal flow improved significantly with the pooled thermal water, radon alone, and ISCS subgroups. For the IgE parameter only sulphurous thermal water (P < 0.01) and ISCS (P > 0.01) were analyzable. Adverse events of minor character were only reported for sulphurous treatment (19/370). Conclusion. Thermal water applications with radon or sulphur can be recommended as additional nonpharmacological treatment in upper airway diseases. Also in comparison to isotonic saline solution it shows significant improvements and should be investigated further.

This study aimed to investigate symptom reduction via the liposomal nasal spray LipoNasal (LN) in patients with rhinitis sicca. Tolerability and the impact on quality of life were also examined. The same parameters were established in parallel for treatment approaches with Bepanthen (BP) nasal ointment containing dexpanthenol and the Rhinomer (RH) nasal spray containing NaCl. This prospective, controlled, open-label observation study was a multicenter trial. 92 patients with rhinitis sicca were allocated to three arms according to their symptoms: LN: n = 33; BP: n = 32 and RH: n = 27. The study comprised three visits at an interval of 14 days. Efficacy was examined by the Rhinitis Sicca Symptom Score (RSSS) documented daily and at the visits based on an endoscopic evaluation. The nasal spray sensory scale was used to investigate the tolerability. Quality of life (QoL) was measured by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the "Short Form 12" of the "Impact on Health-Related Quality of Life (HRQL)" questionnaire on general quality of life. Nasal symptoms improved significantly (p = 0.001) under all three treatment approaches, reflected by the reduction in the RSSS and the Endoscopy Sum Score. A comparison of the three groups showed that no therapy was significantly superior to any of the others (p = 0.410). The tolerability of all treatments was good. Concerning the nasal moisturization, LipoNasal was evaluated better than Bepanthen and Rhinomer. Quality of life improved in all groups, but not significantly. The results show good efficacy and tolerability of the liposomal nasal spray compared to generally recognized treatments of rhinitis sicca with dexpanthenol nasal ointment and NaCl nasal spray. LipoNasal therefore constitutes a good treatment for patients suffering from dry nose.

Background: Allergic rhinitis represents a worldwide health problem. The prevalence is increasing. The aim of this study was to analyse the correlation between the severity of allergic rhinitis and an adequate treatment dose of modern oral antihistamines., Methods: From a comprehensive databank containing data from ten different open-label prospective observational studies including raw data of 140,853 patients with allergic rhinitis, symptomatology variables were analysed and scored to study the effects of treatment with four antihistamines (Desloratadine, Ebastine, Fexofenadine, Levocetirizine) alone or in combination with intranasal corticosteroids. The patient data were collected in 23,606 study centres from Germany, mostly medical specialist and some primary care physicians in private practice. The analyses were performed via individual patient data meta-analysis techniques., Results: Finally 92,900 patient data from nine of ten studies could be analysed. One study with data of 47,953 patients was excluded due to incomplete treatment documentation. Both monotherapy analysis subgroups (Total Symptom Score and Total Nasal Symptom Score) were significantly better than those of their combinations with intranasal steroids. Monotherapy with levocetirizine was determined to be significantly more effective in lowering the Total Symptom Score (p < 0.001) and the Total Nasal Symptom Score (p < 0.05) than the other antihistamines. In the next stage, a greater positive effect of levocetirizine was demonstrated in relation to the severity of the clinical symptoms of allergic rhinitis (Total Nasal Symptom Score in cases with severe symptomatology [effect size = -0.09])., Conclusions: Levocetirizine asserted itself as the only antihistamine compared with the others as significant in this analysis. The study authors recommend monotherapy with the new-generation antihistamine levocetirizine, especially in severe cases of allergic rhinitis.

This systematic review aims first to summarize the previous areas of application of computational fluid dynamics (CFD) and then to demonstrate that CFD is also a suitable instrument for generating three-dimensional images that depict drug effects on nasal mucosa. Special emphasis is placed on the three-dimensional visualization of the antiobstructive effect of nasal steroids and antihistamines in the treatment of allergic rhinitis. In the beginning, CFD technology was only used to demonstrate physiological and pathophysiological airflow conditions in the nose and to aid in preoperative planning and postoperative monitoring of surgical outcome in the field of rhinosurgery. The first studies using CFD examined nasal respiratory physiology, important functions of the nose, such as conditioning and warming of inspired air, and the influence of pathophysiological changes on nasal breathing. Also, postoperative outcome of surgical procedures could be "predicted" using the nasal airflow model. Later studies focused on the three-dimensional visualization of the effect of nasal sprays in healthy subjects and postoperative patients. A completely new approach, however, was the use of CFD in the area of allergic rhinitis and the treatment of its cardinal symptom of nasal obstruction. In two clinical trials, a suitable patient with a positive history of allergic rhinitis was enrolled during a symptom-free period after the pollen season. The patient developed typical allergic rhinitis symptoms after provocation with birch pollen. The 3-D visualization showed that the antiallergic treatment successfully counteracted the effects of nasal allergen provocation on nasal airflow. These observations were attributed to the antiobstructive effect of a nasal steroid (mometasone furoate) and a systemic antihistamine (levocetirizine), respectively. CFD therefore constitutes a non-invasive, precise, reliable and objective examination procedure for generating three-dimensional images that depict the effects of drugs used in the treatment of allergic rhinitis.

Mucosal barrier disorders play an important role in the pathomechanism of the allergic disease. A new approach for their treatment uses liposomes, which consist of phospholipids that make up 75% of the protective nasal surfactant layer. Our aim was to investigate the efficacy of liposomal-based therapy, as a comprehensive treatment alternative to guideline cromoglycate-based therapy, in the treatment of seasonal allergic rhinoconjunctivitis (SAR). We compared nasal and conjunctival symptom reduction with LipoNasal n nasal spray used as monotherapy (LNM), or LipoNasal n nasal spray and Tears Again eye spray combination therapy (LTC), against standard cromoglycate combination therapy (CGC). This prospective, controlled, open observational study was conducted monocentrically. According to their symptoms and preferences 72 patients with SAR were distributed in three equal groups. The study comprised two visits at an interval of 7 days. The efficacy was examined by daily documenting nasal and conjunctival symptom scores. The Nasal-Spray-Sensory-Scale and the Eye-Drops/Spray-Sensory-Scale were used to investigate the tolerability. Quality of life (QoL) was evaluated, using the RHINASTHMA QoL German adapted version. LNM achieved significant improvement in nasal (p < 0.001) and conjunctival symptoms (p = 0.050). The symptom reduction using CGC was equally significant. LTC led to significant nasal symptom relief (p = 0.045). QoL did not improve significantly in all groups (p > 0.05). The tolerability of all treatments was good and no adverse reactions were observed. In all treatment groups the improvement of the nasal and conjunctival symptom scores exceeds the minimal clinically important difference (MCID). The results demonstrate good tolerability and efficacy of non-pharmaceutical liposomal-based treatment (LipoNasal n and Tears Again), given as monotherapy or combination therapy, for nasal and conjunctival symptoms caused by SAR. This study indicates that liposomal-based treatment for SAR may be a comparable alternative to cromoglycate therapy. Further studies are needed to verify these findings.

Background: Oral antihistamines are considered the gold standard therapy for allergic rhinitis to date. The goal of this investigation is to make an indirect comparison between loratadine, an oral antihistamine available over-the-counter (OTC) in the USA, and the more modern antihistamine levocetirizine. Only double-blind, placebo-controlled (DBPC) studies involving monotherapy with the active substances levocetirizine and loratadine were included in the meta-analysis., Methods: The medical databases EMBASE and Medline were searched systematically for all relevant studies completed by the end of 2009. Only DBPC studies conducted in normal environmental settings were included. Furthermore, the Jadad scale was used to guarantee the quality of the studies involved. The "standardized mean difference" (SMD) method was applied for calculating the study-specific effects to neutralize the variability between studies., Results: The results of a total of seven published DBPC studies met all criteria for inclusion in meta-analysis. The meta-analysis showed that levocetirizine was significantly more effective than loratadine in improving the total symptom score (TSS) (p < 0.01). The effect sizes were calculated as -0.59 (95% confidence interval -0.89, -0.29) for levocetirizine and -0.21 (95% confidence interval -0.31, -0.1) for loratadine when compared to placebo., Conclusions: The results of this meta-analysis illustrate greater effectiveness for treatment with the active substance levocetirizine as monotherapy in reducing allergic symptoms when compared to treatment with loratadine.

Lais® allergoid tablets contain allergens that are modified by carbamylation. Due to their modified chemical structure, they are suitable for sublingual immunotherapy (SLIT) (13, 16, 17, 24). Based on their small molecule size of 12 to 40 kDa, they can be easily absorbed via the oral mucosa (1). In this review, we studied the efficacy of SLIT with carbamylated monomeric allergoid tablets in the treatment of grass pollen- and dust mite-induced allergic rhinoconjunctivitis on the basis of symptom and medication score improvements. Following a selective internet and databank search, six trials-some placebo-controlled-regarding the treatment of grass pollen- (n = 266) and dust mite-induced (n = 241) allergic rhinoconjunctivitis were used to draw conclusions regarding the clinical efficacy of allergoid tablets. The primary endpoints in these trials were decreases in the need for allergy medications and/or reductions in the occurrence of rhinoconjunctivitis symptoms. Data was recorded from patient diaries regarding their symptoms and medications used and conclusions were then drawn about the effectiveness and tolerabieity of Lais® tablets. The average improvement in symptom score in three trials of grass pollen allergy treatment was 34% in comparison to the placebo group. The treatment of dust mite-induced rhinoconjunctivitis produced an average symptom score improvement of 22% compared to the placebo or control groups. The intake of symptomatic rescue medication during allergoid tablet therapy declined. Treatment of grass pollen allergies and dust mite-induced rhinoconjunctivitis showed an average medication score improvement of 49% and 24%, respectively. Few side effects were documented in the trials and predominantly local effects were observed. Severe systemic side effects did not occur. On the basis of the trial results summarized in this review, we suggest that SLIT using Lais® sublingual tablets is an effective and well-tolerated form of treatment.

Inflammations of the external auditory canal number among the most frequently occurring ear-nose-throat diseases. For local treatment, substances from various groups of active ingredients are used as combinations and as single-agent drugs, e.g. antibiotics, glucocorticoids or analgesics [1]. In the case of acute otitis externa, treatment measures focus on the reduction of pain and swelling. The study described here investigates the efficacy and safety of glycerol lidocaine eardrops for the treatment of acute abacterial otitis externa (CAS No. for glycerol: 56-81-5, lidocaine-HCl: 73-78-9). In this double-blind, three-arm study, 105 patients diagnosed with acute abacterial otitis externa were included and randomized to receive either glycerol eardrops, glycerol eardrops with 0.5% lidocaine, or glycerol eardrops with 2% lidocaine for seven days. The primary outcome parameter was the change of the five typical clinical symptoms, earache, itching, otorrhea, hearing impairment, and "clogged ear" at Visit 2 (Day 7) based on the initial examination on Day 0. Both therapy groups treated with a combination of glycerol and lidocaine exhibited definite improvement in overall symptoms after seven days. This improvement differed from the mild reduction of symptoms under treatment with glycerol eardrops alone. Overall improvement of symptoms, expressed by the area under the curve of the baseline-adjusted symptom sum score, yielded a mean value of 10.95 (standard deviation 27.4) for the morning survey of the groups receiving eardrops containing only glycerol; in comparison, for eardrops containing glycerol and 2% lidocaine it was 15.71 (+/- 23.6) and for glycerol with 0.5% lidocaine, 23.16 (+/- 19.4). No severe adverse events occurred. Five adverse events were documented during the clinical investigation, none of which was considered by the investigators to be related to the study medication. Local therapy with glycerol lidocaine eardrops is a safe, and cost-effective treatment for the widely spread clinical picture of acute abacterial otitis externa. The advantage regarding efficacy of this combination compared with glycerol eardrops must be demonstrated in an adequately powered clinical trial.