Results of the Cologne Corona Surveillance (CoCoS) project- a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection, and moderate-to-severe course in primarily immunized adults.

BACKGROUND: Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. METHODS: The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants' demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. RESULTS: A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415-0.823) and older age (HR = 0.974, 95%CI 0.966-0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949-0.977). Female sex (HR = 2.570, 95%CI1.435-4.603), smoking (HR = 1.965, 95%CI1.147-3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465-5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. CONCLUSION: The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Results of the Cologne Corona Surveillance (CoCoS) study - a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection in adults.

BACKGROUND: The personal, environmental, and behavioral risk factors that play an important role in the spread of SARS-CoV-2 are still largely unclear. At the same time, there is limited evidence on the effectiveness of specific countermeasures for SARS-CoV-2. As a first approach to these questions, we use data from the Cologne Corona Surveillance (CoCoS) study, a large cross-sectional study conducted in Cologne, Germany, in June 2021. METHODS: This study was conducted in Cologne, Germany. Six thousand randomly selected Cologne residents who were 18 years of age or older were invited to participate in this study. Participant information was obtained via an online survey. Previous SARS-CoV-2 infections were recorded using self-reports. Sociodemographic and environmental information such as age, sex, living situation were collected. Potential SARS-CoV-2 risk behaviors were captured (workplace situation, adherence to hygiene regulations, and regular use of public transportation). Adherence to hygiene regulations was surveyed by determining the compliance with the 'AHA'-rules (German acronym that stands for keeping a distance of 1.5 m from fellow citizens, hand disinfection, and wearing a face mask). Binary logistic regression analysis was used to identify risk factors for SARS-CoV-2 infection. RESULTS: A sample of 2,433 study participants provided information. Comparison of the sample with the general population showed representativeness for most sociodemographic characteristics with a preference for higher level of education in the study sample. Younger age, as well as living with minor children (under 18 years) in the same household were associated with a higher number of self-reported SARS-CoV-2 infections. Adherence to hygiene regulations was associated with fewer self-reported SARS-CoV-2 infections in adults. Gender, size of living space per person, workplace situation (work from home versus working with contact to colleagues/customers), and regular use of public transportation showed no significant association with self-reported SARS-CoV-2 infections in multivariable analysis. CONCLUSION: The presented results provide initial indications of which sociodemographic and behavioral factors may be associated with SARS-CoV-2 infection. However, the fact that these factors were recorded without exact dates and could have changed accordingly during the pandemic or after infection limits the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Apathy in patients with Alzheimer's disease is a cost-driving factor.

BACKGROUND: Apathy is the most frequent neuropsychiatric symptom in patients with dementia of the Alzheimer's type (DAT). We analyzed the influence of apathy on the resource use of DAT patients and their caregivers. METHODS: Included were baseline data of 107 DAT patients from a randomized clinical trial on apathy treatment. The Resource Utilization in Dementia (RUD) instrument assessed costs over a 1-month period prior to baseline. Cost predictors were determined via a least absolute shrinkage and selection operator (LASSO). RESULTS: On average, total monthly costs were €3070, of which €2711 accounted for caregivers' and €359 for patients' costs. An increase of one point in the Apathy Evaluation Scale resulted in a 4.1% increase in total costs. DISCUSSION: Apathy is a significant cost driving factor for total costs in mild to moderate DAT. Effective treatment of apathy might be associated with reduced overall costs in DAT.

Results of the Cologne Corona surveillance (CoCoS) study - a prospective population-based cohort study: incidence data and potential underestimation of new SARS-CoV-2 adult infections by health authorities.

BACKGROUND: Current incidence estimates of SARS-CoV-2 in Germany rely to a large extent on case notifications. However, the large number of mild or asymptomatic infections is likely to result in underestimation. Population-based studies can provide valid estimates of the SARS-CoV-2 incidence and thus support health authorities to monitor the epidemiological situation and to initiate, maintain, strengthen or relax effective countermeasures. METHODS: This study was conducted in Cologne, Germany. Six-thousand randomly drawn Cologne residents, 18 years of age or older, were contacted by mail in March 2021. Study envelopes contained a kit for self-administered saliva sample and access details to a questionnaire on sociodemographic characteristics, previous positive SARS-CoV-2 RT-qPCR and completed COVID-19 vaccinations. Participants were again invited for a second round in June 2021, while those who declined participation were replaced by additional randomly drawn Cologne residents in order to reach a total of 6000 potential participants again. The saliva samples were sent to the laboratory by mail and tested for SARS-CoV-2 using RT-qPCR. The incidence estimates were adjusted for sensitivity and specificity of the test procedure and compared with the official numbers of new SARS-CoV-2 cases in the adult Cologne population. RESULTS: The first surveillance round in March 2021 (response rate: 34.08%, N = 2045) showed a SARS-CoV-2 seven-day incidence of 85 cases per 100,000 adult Cologne residents (95% CI: 9 to 319). In the same period, the officially registered cases were 125 per 100,000. The second surveillance round in June 2021 (response rate: 36.53%, N = 2192) showed a seven-day incidence of 27 per 100,000 adult Cologne residents (95% CI: 1 to 142), while the official figures for newly registered SARS-CoV-2 cases in the same period were 15 per 100,000. CONCLUSIONS: The incidence estimates do not indicate relevant underestimation of new SARS-CoV-2 infections based on case notification. Regular use of the surveillance method developed here may nevertheless complement the efforts of the health authorities to assess the epidemiological situation. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046 , Registered on 25 February 2021.

Is trained communication about desire to die harmful for patients receiving palliative care? A cohort study.

BACKGROUND: Palliative patients frequently express a desire to die. Health professionals report uncertainty regarding potential risks of addressing it. AIM: We aim to evaluate effects of desire to die-conversations on palliative patients. DESIGN: Within a prospective mixed-methods cohort study, we trained health professionals in dealing with desire to die. Afterwards, they held conversations about it with patients. Effects on depressiveness, hopelessness, wish to hasten death, death anxiety, patient-health professional-relationship, and will to live were evaluated at baseline (t0), 1 (t1), and 6 weeks afterwards (t2). Results were analyzed descriptively. SETTING/PARTICIPANTS: From April 2018 to March 2020, 43 health professionals asked 173 patients from all stationary and ambulatory palliative care settings (within 80 km radius) for participation. Complete assessments were obtained from n = 85 (t0), n = 64 (t1), and n = 46 (t2). RESULTS: At t1, patients scored significantly lower on depressiveness (med = 8, M = 8.1, SD = 5.4) than at t0 (med = 9.5, M = 10.5, SD = 5.8) with Z = -3.220, p = 0.001 and Cohen's d = 0.42. This was due to medium-severely depressed patients: At t1, their depressiveness scores decreased significantly (med = 9, M = 9.8; SD = 5.1) compared to t0 (med = 14, M = 15.2; SD = 3.9) with Z = -3.730, p ⩽ 0.000 and Cohen's d = 1.2, but others' did not. All other outcomes showed positive descriptive trends. CONCLUSIONS: Desire to die-conversations through trained health professionals do not harm palliative patients. Results cautiously suggest temporary improvement.

Impaired vascular endothelial function as a perioperative risk predictor - a prospective observational trial.

BACKGROUND: In the recent years, an increasing number of patients with multiple comorbidities (e.g. coronary artery disease, diabetes, hypertension) presents to the operating room. The clinical risk factors are accompanied by underlying vascular-endothelial dysfunction, which impairs microcirculation and may predispose to end-organ dysfunction and impaired postoperative outcome. Whether preoperative endothelial dysfunction identifies patients at risk of postoperative complications remains unclear. In this prospective observational study, we tested the hypothesis that impaired flow-mediated dilation (FMD), a non-invasive surrogate marker of endothelial function, correlates with Days at Home within 30 days after surgery (DAH30). DAH30 is a patient-centric metric that captures postoperative complications and importantly also hospital re-admissions. METHODS: Seventy-one patients scheduled for major abdominal surgery were enrolled. FMD was performed pre-operatively prior to major abdominal surgery and patients were dichotomised at a threshold value of 10%. FMD was then correlated with DAH30 (primary endpoint) and postoperative complications (secondary endpoints). RESULTS: DAH30 did not differ between patients with reduced FMD and normal FMD (14 (4) (median (IQR)) vs. 15 (8), P = 0.8). Similary, no differences between both groups were found for CCI (normal FMD: 21 (30) (median (IQR)), reduced FMD: 26 (38), P = 0.4) or frequency of major complications (normal FMD: 7 (19%) (n (%)), reduced FMD: 12 (35%), P = 0.12). The regression analyses revealed that FMD in combination with ASA status and surgery duration had no additional significant predictive effect for DAH30, CCI or Clavien-Dindo score. CONCLUSION: FMD does not add predictive value with regards to DAH30, CCI or Clavien-Dindo score within our study cohort of patients undergoing abdominal surgery. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register ( DRKS00005472 ), prospectively registered on 25/11/2013.

Protocol of the Cologne Corona Surveillance (CoCoS) Study- a prospective population-based cohort study.

BACKGROUND: Surveillance strategies are critical to cope with the current SARS-CoV-2 pandemic and to evaluate, as well as adjust government-imposed countermeasures. Incidence estimates are widely based on laboratory confirmed cases reported by health authorities. Prevalence and incidence data of SARS-CoV-2 is still scarce, along with demographic and behavioural factors associated with infection risk. METHODS: The Cologne Corona Surveillance Study will be conducted in the City of Cologne, which is the fourth-largest city in Germany with a population of approximately 1.1 million. Researchers will apply self-sampling surveillance to a rolling cohort of Cologne residents. Random samples of 6000 Cologne residents 18 years of age and older will be drawn from the registration office. Upon receiving the information and saliva sample kit, participants will be asked to fill out a questionnaire online or via phone, sign written informed consent, and send back written consent, as well as saliva sample. The saliva samples will be tested for SARS-CoV-2 by reverse PCR. The questionnaire will be administered to gather information about personal characteristics such as health status and risks. A second round of testing will take place 6 weeks after the first. DISCUSSION: Self-administered saliva sampling proved to be a legitimate and feasible alternative to nasopharyngeal swabs taken by health professionals. However, it is unclear whether the targeted response rate of 40% can be achieved and whether the results are representative of the population. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046 , Registered on 25 February 2021.

Vascular tone regulation in renal interlobar arteries of male rats is dysfunctional after intrauterine growth restriction.

Intrauterine growth restriction (IUGR) due to an adverse intrauterine environment predisposes to arterial hypertension and loss of kidney function. Here, we investigated whether vascular dysregulation in renal interlobar arteries (RIAs) may contribute to hypertensive glomerular damage after IUGR. In rats, IUGR was induced by bilateral uterine vessel ligation. Offspring of nonoperated rats served as controls. From postnatal day 49, blood pressure was telemetrically recorded. On postnatal day 70, we evaluated contractile function in RIAs and mesenteric arteries. In addition, blood, urine, and glomerular parameters as well as renal collagen deposition were analyzed. IUGR RIAs not only showed loss of stretch activation in 9 of 11 arteries and reduced stretch-induced myogenic tone but also showed a shift of the concentration-response relation of acetylcholine-induced relaxation toward lower concentrations. However, IUGR RIAs also exhibited augmented contractions through phenylephrine. Systemic mean arterial pressure [mean difference: 4.8 mmHg (daytime) and 5.7 mmHg (night)], mean glomerular area (IUGR: 9,754 ± 338 µm2 and control: 8,395 ± 227 µm2), and urinary protein-to-creatinine ratio (IUGR: 1.67 ± 0.13 g/g and control: 1.26 ± 0.10 g/g) were elevated after IUGR. We conclude that male IUGR rat offspring may have increased vulnerability toward hypertensive glomerular damage due to loss of myogenic tone and augmented endothelium-dependent relaxation in RIAs.NEW & NOTEWORTHY For the first time, our study presents wire myography data from renal interlobar arteries (RIAs) and mesenteric arteries of young adult rat offspring after intrauterine growth restriction (IUGR). Our data indicate that myogenic tone in RIAs is dysfunctional after IUGR. Furthermore, IUGR offspring suffer from mild arterial hypertension, glomerular hypertrophy, and increased urinary protein-to-creatinine ratio. Dysregulation of vascular tone in RIAs could be an important variable that impacts upon vulnerability toward glomerular injury after IUGR.

Bupropion for the Treatment of Apathy in Alzheimer Disease: A Randomized Clinical Trial.

Importance: Apathy is a frequent neuropsychiatric symptom in dementia of Alzheimer type and negatively affects the disease course and patients' and caregivers' quality of life. Effective treatment options are needed. Objective: To examine the efficacy and safety of the dopamine and noradrenaline reuptake inhibitor bupropion in the treatment of apathy in patients with dementia of Alzheimer type. Design, Setting, and Participants: This 12-week, multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted in a psychiatric and neurological outpatient setting between July 2010 and July 2014 in Germany. Patients with mild-to-moderate dementia of Alzheimer type and clinically relevant apathy were included. Patients with additional clinically relevant depressed mood were excluded. Data analyses were performed between August 2018 and August 2019. Interventions: Patients received either bupropion or placebo (150 mg for 4 weeks plus 300 mg for 8 weeks). In case of intolerability of 300 mg, patients continued to receive 150 mg throughout the study. Main Outcomes and Measures: Change on the Apathy Evaluation Scale-Clinician Version (AES-C) (score range, 18-72 points) between baseline and week 12 was the primary outcome parameter. Secondary outcome parameters included measures of neuropsychiatric symptoms, cognition, activities of daily living, and quality of life. Outcome measures were assessed at baseline and at 4, 8, and 12 weeks. Results: A total of 108 patients (mean [SD] age, 74.8 [5.9] years; 67 men [62%]) were included in the intention-to-treat analysis, with 54 randomized to receive bupropion and 54 randomized to receive placebo. The baseline AES-C score was comparable between the bupropion group and the placebo group (mean [SD], 52.2 [8.7] vs 50.4 [8.2]). After controlling for the baseline AES-C score, site, and comedication with donepezil or galantamine, the mean change in the AES-C score between the bupropion and placebo groups was not statistically significant (mean change, 2.22; 95% CI, -0.47 to 4.91; P = .11). Results on secondary outcomes showed statistically significant differences between bupropion and placebo in terms of total neuropsychiatric symptoms (mean change, 5.52; 95% CI, 2.00 to 9.04; P = .003) and health-related quality of life (uncorrected for multiple comparisons; mean change, -1.66; 95% CI, -3.01 to -0.31; P = .02) with greater improvement in the placebo group. No statistically significant changes between groups were found for activities of daily living (mean change, -2.92; 95% CI, -5.89 to 0.06; P = .05) and cognition (mean change, -0.27; 95% CI, -3.26 to 2.73; P = .86). The numbers of adverse events (bupropion group, 39 patients [72.2%]; placebo group, 33 patients [61.1%]) and serious adverse events (bupropion group, 5 patients [9.3%]; placebo group, 2 patients [3.7%]) were comparable between groups. Conclusions and Relevance: Although it is safe, bupropion was not superior to placebo for the treatment of apathy in patients with dementia of Alzheimer type in the absence of clinically relevant depressed mood. Trial Registration: EU Clinical Trials Register Identifier: 2007-005352-17.

The desire to die in palliative care: a sequential mixed methods study to develop a semi-structured clinical approach.

BACKGROUND: Although desire to die of varying intensity and permanence is frequent in patients receiving palliative care, uncertainty exists concerning appropriate therapeutic responses to it. To support health professionals in dealing with patients´ potential desire to die, a training program and a semi-structured clinical approach was developed. This study aimed for a revision of and consensus building on the clinical approach to support proactively addressing desire to die and routine exploration of death and dying distress. METHODS: Within a sequential mixed methods design, we invited 16 palliative patients to participate in semi-structured interviews and 377 (inter-)national experts to attend a two-round Delphi process. Interviews were analyzed using qualitative content analysis and an agreement consensus for the Delphi was determined according to predefined criteria. RESULTS: 11 (69%) patients from different settings participated in face-to-face interviews. As key issues for conversations on desire to die they pointed out the relationship between professionals and patients, the setting and support from external experts, if required. A set of 149 (40%) experts (132/89% from Germany, 17/11% from 9 other countries) evaluated ten domains of the semi-structured clinical approach. There was immediate consensus on nine domains concerning conversation design, suggestions for (self-)reflection, and further recommended action. The one domain in which consensus was not achieved until the second round was "proactively addressing desire to die". CONCLUSIONS: We have provided the first semi-structured clinical approach to identify and address desire to die and to respond therapeutically - based on evidence, patients' views and consensus among professional experts. TRIAL REGISTRATION: The study is registered in the German Clinical Trials Register (DRKS00012988; registration date: 27.9.2017) and in the Health Services Research Database (VfD_DEDIPOM_17_003889; registration date: 14.9.2017).

Pharmaco-epidemiological research on herbal medicinal products in the paediatric population: data from the PhytoVIS study.

In paediatrics, clinical study data are limited, especially on herbal medicinal products. To address this gap, 2063 datasets from the paediatric population were evaluated in the PhytoVIS data base. By screening for paediatric data, information on indication, gender, treatment, co-medication and tolerability were evaluated. The majority of patients was treated because of common cold, fever, digestive complaints, skin diseases, sleep disturbances and anxiety. The perceived effect of the therapy was rated in 84% of the patients as very good or good without adverse events. The data shed light on a still neglected field of phyto-pharmacotherapy by giving information on the use of herbal medicines in an unselected cohort of paediatric patients. The results confirm the good clinical effects and safety of herbal medicinal products in this patient population and show that they are widely used in Germany.What is Known:• In Germany, about 85% of children receive one or more herbal medicinal products per year.• Despite international initiatives to promote clinical research in paediatrics, there are still many gaps of knowledge in the use of drugs in paediatrics.What is New:• The PhytoVIS project evaluated 2063 data sets from the paediatric population using herbal medicinal products.• The majority of patients was treated because of common cold, fever, digestive complaints, skin diseases, sleep disturbances and anxiety, and 84% of the patients rated the therapy as very good or good without adverse events.

Shortened up-dosing with sublingual immunotherapy drops containing tree allergens is well tolerated and elicits dose-dependent clinical effects during the first pollen season.

BACKGROUND: This study compared a rapid home-based up-dosing schedule for sublingual immunotherapy (SLIT) drops containing tree pollen allergens with two previously established schedules. Furthermore, the clinical effect of the SLIT was investigated with respect to patients' first pollen season under treatment. METHODS: In this open-label, prospective, patient-preference, non-interventional study, local and systemic reactions were compared between three up-dosing groups using a SLIT formulation containing birch, alder, and hazel pollen extracts (ORALVAC® Compact Bäume). Clinical improvement after patients' first season under treatment was analysed using symptom scores, ARIA classification, symptom control, and the use of symptomatic medication and was compared with data from the previous, pre-treatment pollen season. As the real-life study design allowed no placebo group, the late-treated patients (co-seasonal) served as a control, and crowd-sourced symptom data from persons with hay fever were used from a free web-based online diary. RESULTS: In 33 study centres in Germany and Austria, 164 patients were included. The treatment was well tolerated, without difference between the groups during the up-dosing phase. At the end of the assessment, 96.1% rated the tolerability of the treatment as good or very good. Local reactions were mostly mild in severity and no serious adverse events occurred. Symptom scores decreased from the 2016 pollen season to the 2017 pollen season. As for the ARIA classification, 79.0% of patients had persistent, moderate-to-severe rhinitis before treatment, but only 18.6% had the same classification after treatment. In all, 62.4% of patients achieved symptom control, and 34.3% of patients required no symptomatic medication after treatment. The rhinoconjunctivitis score was 34.4% lower for pre-seasonal treatment initiation than for the control group. Crowd-sourced symptom load indices showed that the 2016 season caused slightly more symptoms; however, it is assumed that this difference of 0.3-0.5 (score range 0-10) was of less clinical relevance. CONCLUSION: The treatment administered using the rapid home-based up-dosing schedule was safe and well tolerated. Symptom relief and reduction in medication use were observed during the first pollen season with SLIT. TRIAL REGISTRATION NUMBER: NCT03097432 (clinicaltrials.gov).

Ectoine-Containing Inhalation Solution versus Saline Inhalation Solution in the Treatment of Acute Bronchitis and Acute Respiratory Infections: A Prospective, Controlled, Observational Study.

PURPOSE: This study investigated an inhalation solution containing ectoine, a bacterial-derived extremolyte, for the treatment of acute bronchitis and acute respiratory infections in comparison with saline inhalation solution. METHODS: This prospective, controlled, observational study comprised an inclusion visit (day 1), a final visit (day 7), and a follow-up questionnaire (day 17). The treatment itself was administered from day 1 to day 7. The Bronchitis Severity Score, patients' general health, general effectiveness of the treatment, tolerability, and adverse events were compared between two groups. RESULTS: In total, 135 patients were recruited; 79 patients received ectoine inhalation solution and 56 saline inhalation solution. After treatment, symptom scores decreased significantly in both groups (P < 0.05); the reduction in symptom scores was slightly greater in the ectoine group than in the saline group. The first significant reduction in symptom scores (P < 0.05) occurred earlier in the ectoine group than in the saline group. The differences in the area under the curve for the symptoms of dyspnea and auscultation findings were significant in favor of ectoine (P < 0.05). After treatment, more patients and physicians in the ectoine group assessed their or their patients' condition as "completely recovered" or "greatly improved" than those in the saline group. Almost all patients and physicians assessed the tolerability of both treatments as "good" or "very good". CONCLUSIONS: Ectoine inhalation solution seems to be slightly more effective than saline inhalation solution for the treatment of acute bronchitis and acute respiratory infections.

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.

Impaired sports performance of athletes suffering from pollen-induced allergic rhinitis: a cross-sectional, observational survey in German athletes.

BACKGROUND: Allergic rhinitis has major impacts on sports performance of athletes. The present study aimed at determining the frequency of seasonal pollen allergy and analyzing the impacts of pollen allergy, the choice of allergy treatments and their benefits for sports performance in a group of professional and recreational athletes. METHODS: The study was conducted as a self-reported questionnaire survey. Subjects were recruited from the German Sport University and the Cologne Marathon 2014 during the peak pollen season of 2014. RESULTS: Athletes returned 636 completed questionnaires, 42.6% of participants reported suffering from a pollen allergy and 30.2% also suffered from asthma. Performance impairments were reported in more than 80% of allergic subjects. In all, 82.2% of subjects used symptomatic medications, 32.3% alternative therapies, and 47.6% allergen immunotherapy. Subjects who used immunotherapy had fewer impaired training bouts than those who used symptomatic and alternative therapies. The majority of subjects had concerns about allergy treatment such as side effects, negative impacts on sports performance and lack of long-term effects. CONCLUSIONS: This study confirmed a high prevalence of pollen allergy among German athletes. The majority of allergic rhinitis athletes were undertreated, and the reason could be their reservations about allergy treatments. Pollen allergy tremendously reduced sports performance of athletes during the pollen season. This impact can be lessened with proper treatment such as immunotherapy. Better understanding of available treatment modalities should be provided to patients and physicians to improve sports performance of athletes suffering from pollen allergy.

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

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).

Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients.

AIM: To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. METHODS: In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. RESULTS: Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. CONCLUSION: This study found 1000 UA/day to be the optimal effective and safe dose.

Dexpanthenol: An Overview of its Contribution to Symptom Relief in Acute Rhinitis Treated with Decongestant Nasal Sprays.

Nasal blockage is the most bothersome symptom of acute rhinitis. Nasal decongestant sprays containing alpha-sympathomimetics, such as oxymetazoline and xylometazoline, have a rapid onset of action. However, this effect decreases with repeated application and, furthermore, the ciliary function of the nasal mucosa is practically paralyzed. Dexpanthenol promotes cell proliferation and protects the epithelium. Combining these two agents has demonstrated beneficial synergetic effects on the symptoms of acute rhinitis. In a post hoc analysis of a large-scale double-blind, active-controlled study including 152 patients, we could demonstrate that the benefit of added dexpanthenol appears as early as on the third day of the combined application of xylometazoline and dexpanthenol in terms of complete or near-to-complete freedom from symptoms. After 5 days, 47% of the patients were cured under the combined treatment compared with only 1% under xylometazoline monotherapy. These data show that the addition of dexpanthenol to an alpha-sympathomimetic nasal spray not only improves its tolerability but also further increases its effectiveness and leads to expedited cure. FUNDING: Klosterfrau Healthcare Group.

Management of Grass Pollen Allergy with 5-Grass Pollen Tablet: Results of a 2-Year Real-Life Study.

INTRODUCTION: Allergen immunotherapy is the only treatment option for allergic rhinitis with disease-altering potential. It was the objective of this study to assess the effectiveness and tolerability of a 5-grass pollen tablet in a large population of non-selected grass pollen allergic patients, i.e. patients with different clinical profiles in daily clinical practice. METHODS: In a 2-year, prospective, open-label, multicenter, non-controlled, observational study patients were included from 327 centers across Germany. Rhinoconjunctivitis symptoms, symptomatic medication intake and adverse events were recorded. RESULTS: A total of 1482 patients aged 4-75 years were included. During the 2-year period of 5-grass pollen tablet therapy, mean rhinoconjunctivitis score decreased significantly in the overall study population by 65.5% (P < 0.001). The percentage of patients taking symptomatic medication decreased from 83.8% to 42.7%. Mean 2-year improvements in rhinoconjunctivitis scores and decreases in the percentage of patients taking symptomatic medication were broadly similar in adults, adolescents and children, in patients with polyallergy versus monoallergy, and in patients with/without asthma. Among polyallergic patients, concomitant application of another specific immunotherapy did not impair treatment outcomes. Adverse drug reactions, predominantly affecting the local application area, occurred in 15.4% of the overall patient population (n = 229). No cases of anaphylaxis or epinephrine use were documented. CONCLUSION: This study indicates that sublingual immunotherapy with the 5-grass pollen tablet is well tolerated and provides sustained effectiveness over 2 years in patients with different clinical profiles, producing a significant decrease in allergic symptoms and a reduction in the use of symptomatic medication. FUNDING: Stallergenes GmbH.