A real-world study of quality of life following treatment with xylometazoline hydrochloride in individuals with common cold.

BACKGROUND: The common cold is a frequent, acute, and mild upper respiratory human disease. Nasal congestion has been considered the most bothersome symptom in the common cold, impacting quality of life (QoL). Topical decongestants containing steroids benefit QoL in allergic rhinitis, but no published research has assessed the impact of topical decongestants on QoL in the common cold. OBJECTIVE: To evaluate the effects of xylometazoline hydrochloride 0.1% (Otrivin, GSK Consumer Healthcare SARL, Switzerland) for up to 7 days on QoL in participants with nasal congestion associated with the common cold. DESIGN: This was a decentralized, longitudinal, open-label study. METHODS: The study enrolled 136 participants (⩾18 years) with early symptoms of the common cold, of which 102 were included in the modified intention-to-treat (mITT) population. Within 24 h of study product receipt, participants confirmed a 'plugged nose' and ⩾1 other common cold symptom. Primary endpoints were Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) total score, total and individual symptom scores, and total QoL score. Secondary endpoints were additional QoL scores. Exploratory and post hoc analyses included median days to resolution for each QoL factor and analyses of five QoL categories. RESULTS: Consistent improvements in symptoms and QoL were seen in the mITT population. From day 1, improvements were seen in the 'plugged nose' symptom (p = 0.0023), WURSS-21 total QoL score, and all individual QoL scores (p < 0.0001 for all). After the last dose needed, significant improvements were seen in sleep quality (73%), vitality (76%), physical activity (71%), social activity (80%), and sensation (81%). No serious or unexpected adverse events were reported. CONCLUSION: This study is the first to demonstrate in a real-life setting that treating nasal congestion in adults with xylometazoline hydrochloride 0.1% during the common cold positively impacts QoL factors relevant to daily living [Otrivin: Quality of Life (QoL) Impact in a Real-World Setting; https://clinicaltrials.gov/study/NCT05556148].

Impact of xylometazoline hydrochloride 0.1% on quality of life in people with blocked nose associated with the common coldThe common cold is a widespread, mild respiratory illness for which a hallmark symptom is a blocked or stuffy nose, which makes breathing and sleeping difficult. This study focused on how a nasal spray called Otrivin (containing xylometazoline hydrochloride 0.1%) impacts the quality of life (QoL) of people suffering from nasal congestion due to the common cold.Participants answered a questionnaire called the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), which helped understand how people experience respiratory symptoms and how different aspects of QoL were impacted. Participants also responded to eight additional QoL questions not covered in the WURSS-21.The results showed that from the first day of using the nasal spray, participants experienced significant relief from the blocked nose symptom and reported an overall improvement in their QoL and well-being, such as in sleep quality, energy levels, senses, and physical and social activities.In conclusion, this real-world study demonstrated that using xylometazoline hydrochloride 0.1% nasal spray during the common cold can significantly improve nasal congestion and various aspects of a person's daily life. These findings provide valuable evidence for using this nasal spray to relieve symptoms and enhance the overall well-being of individuals with the common cold.

Hemorrhagic stroke caused by xylometazoline poisoning.

An increase in the use of over-the-counter medications has been observed in recent years. This also concerns xylometazoline, approved for the treatment of allergic rhinitis or upper respiratory tract infections. We present the fatal case of a 40 year-old-woman with a massive hemorrhagic stroke. Initial toxicology tests of biological material collected during autopsy revealed the presence of xylometazoline. No other significant toxicology findings were noted. LC-MS/MS method has been developed to determine xylometazoline concentration, which was 18.6 ng/mL in blood and 498.9 ng/mL in urine. The macroscopically detected hemorrhagic focus was confirmed by histopathological which confirmed hemorrhagic infarcts in the brain tissue, especially in the subarachnoid area. No other pathological changes were found. Based on findings from autopsy and toxicological analyses, the direct cause of death was concluded to be hemorrhagic stroke resulting from xylometazoline intoxication. Although xylometazoline products are regarded as relatively safe and are available over the counter, the risk of adverse effects, in particular stroke leading to death, should be considered. If adverse effects are observed, it is reasonable to measure the concentration of the drug in blood and urine. With such data, it will be possible to assess the actual exposure to this xenobiotic and draw firmer conclusions.

Air pollution exposure is associated with rhinitis in older US adults via specific immune mechanisms.

BACKGROUND: Pathophysiology of rhinitis in older adults is largely unknown. We tested whether air pollution is associated with this condition and how immune mechanisms may play a role in this relationship. METHODS: We analyzed cross-sectional data from the National Social Life, Health, and Aging Project, a nationally representative study of older adults born between 1920 and 1947. Particulate matter ≤2.5 µm (PM2.5 ) air pollution exposure estimates were generated using validated spatiotemporal models. Presence of rhinitis was defined based on medication use (≥1: intranasal medications: steroids, antihistamines, lubricants, and/or decongestants, and/or oral medications: antihistamines and/or decongestants). K-means cluster analysis (Jaccard method) was used to group 13 peripheral blood cytokines into 3 clusters to facilitate functional determination. We fitted multivariate logistic regressions to correlate PM2.5 exposure with presence of rhinitis, controlling for confounders, and then determined the role of cytokines in this relationship. RESULTS: Long- (but not short-) term exposure to PM2.5 was associated with presence of rhinitis: 3-year exposure window, odds ratio (OR) = 1.32, 95% confidence interval (CI): 0.98, 1.80, per 1 standard deviation (SD) PM2.5 increase. Inclusion of cytokine cluster in the model led to a modestly stronger effect of PM2.5 exposure on rhinitis (OR = 1.37; 95% CI: 1.00, 1.87; 3-year exposure window). The particular immune profile responsible for this result was composed of elevated IL-3, IL-12, and IFN-γ (OR = 4.86, 95% CI: 1.10, 21.58, immune profile-PM2.5 exposure interaction term). CONCLUSION: We show for the first time that IL-3, IL-12, and IFN-γ explain in part the relationship between PM2.5 exposure and rhinitis in older US adults. If confirmed, these immune pathways may be used as therapeutic targets.

Reduced Use of Antibiotics and Nasal Decongestants During Treatment with a Mouthwash Containing Delmopinol.

PURPOSE: To evaluate the use of concomitant medication in combination with a mouthwash of delmopinol HCl 0.2% based on data from 8 phase III efficacy studies on the mouthwash. MATERIALS AND METHODS: Clinical data obtained from 8 previously performed phase III studies, carried out to document the clinical efficacy of a mouthwash of delmopinol HCl 0.2% with respect plaque and gingivitis, were used to analyse the use of concomitant medication. In these 8 randomised double-blind clinical phase III studies the patients were - in addition to their normal oral hygiene measures - treated for 2-6 months with mouthwashes containing delmopinol HCl 0.2%, delmopinol HCl 0.1%, chlorhexidine digluconate 0.2% or placebo. The number of visits in each study was three. Each time the patients visited the dentist for efficacy determinations, other data were also recorded. One of these was whether the patient had used any other medication during the study. In this paper, the number of treatments of different types of concomitant medication (antibiotics, nasal decongestants and others) was used as a basis for statistical comparisons between the different test groups. RESULTS: For antibiotics (all indications), a 27% lower number of treatments was obtained in the delmopinol 0.2% group in comparison with the placebo group, and a 41% decrease was observed for treatments with antibiotics for respiratory infections. For nasal decongestants, the number of treatments was 53% lower in the delmopinol 0.2% group. CONCLUSIONS: The delmopinol HCl 0.2% solution in patients with gingivitis provided a statistically significant reduction of concomitant use of antibiotics and nasal decongestants.

Chronic nasal dysfunction: A clinical case illustrating the concept in practice.

INTRODUCTION: We illustrate the diagnostic method for chronic nasal dysfunction by an observation in which the clinical history was compared to preoperative responses on the DyNaChron self-administered questionnaire, with ENT interpretation of the sinonasal CT scan preceding and guiding nasal endoscopy. CASE REPORT: The initial suspicion of rhinitis medicamentosa was transformed by the radiological and endoscopic findings of chronic respiratory rhinitis signs. Prick tests showing sensitivity to dust mites then suggested an allergic origin of the mucosal inflammation, which affected neither the olfactory nose nor the paranasal sinuses. A septal deviation hampering visualization of the right ethmoidal reliefs completed the clinical picture. Inferior turbinate hypertrophy secondary to allergic inflammation could have been aggravated by prolonged daily use of nasal vasoconstrictors. Failure of medical treatment combining nasal lavage, topical corticosteroids and an attempt at weaning led to effective medical and surgical management combining septoplasty, bilateral inferior turbinoplasty, continuation of topical corticosteroids and initiation of allergen immunotherapy. In addition to complete relief of nasal obstruction and abandonment of nasal vasoconstrictors, improved sense of smell completed the restoration of nasal comfort. DISCUSSION: It is helpful to conceive the nose as being anatomically and pathophysiologically a triple organ and to evaluate therapy in terms of improvement in each symptom.

Novel nasal formulation of xylometazoline with hyaluronic acid: In vitro ciliary beat frequency study.

Acute viral rhinosinusitis (viral ARS), or commonly referred to as the "common cold", is caused by respiratory viruses that cause disruption of the airway epithelial barrier and mucociliary dysfunction. Treatment of ARS is mainly symptomatic, with xylometazoline, a direct-acting α-adrenoceptor agonist, commonly used as a nasal decongestant. Unfortunately, this treatment does not resolve the epithelial dysfunction observed in ARS, and its use might negatively impact the nasal mucosa causing issues such as dryness, stinging, burning, rebound congestion, as well as atrophy. In light of this, a novel nasal spray formulation containing both xylometazoline and hyaluronic acid (HA) was developed to provide a more effective and safer treatment for viral ARS. HA is a natural polysaccharide known to hydrate and moisturise the upper respiratory tract, maintain the integrity of the nasal mucosa, and promote mucociliary clearance and wound healing. To investigate the potential of this combination, this study was conducted using the nasal MucilAirTMin vitro model and high-speed phase-contrast microscopy to examine the effect of xylometazoline and HA on ciliary function by measuring ciliary beat frequency and their cytotoxicity by morphological, histological and ultrastructural analysis. This research is the first to assess the effects of a specific dose and molecular weight of HA as an active pharmaceutical ingredient in nasal spray formulations. The combination of a fast-acting decongestant and an additional active agent targeting nasal epithelial dysfunction has the potential to provide an improved, reliable and safe treatment for viral ARS, and may serve as the basis for future clinical studies.

[Methodology for the use of kinesiological decongestant dressing in double-jaw orthognathic operations]. / Metodika primeneniya kineziologicheskoi protivootechnoi povyazki pri dvukhchelyustnykh ortognaticheskikh operatsiyakh.

OBJECTIVE: Development and implementation in practice of a technique for applying a postoperative decongestant kinesiological bandage. MATERIALS AND METHODS: A comparative analysis of the effectiveness of the developed methodology was carried out. Three groups of patients were formed, consisting of 20 people. The first group of patients received a kinesiological bandage after surgery. The second group used a pressure bandage, while the third group used a chilotherapeutic cooling mask. RESULTS: The average value of the volume of postoperative edema (in cm) on the 5th day after surgery was 10.9 in the first group; 11.4 in the second group; 11.1 in the third group. On the 10th day the corresponding values were 10.7, 11.2 and 11 cm in the third group. CONCLUSIONS: The revealed indicators of average values in the three studied groups proved that the proposed method of applying the decongestant kinesiology dressing has the most pronounced effectiveness in the postoperative period.

Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment.

BACKGROUND AND OBJECTIVES: Nasal esketamine is indicated for the treatment of adults with treatment-resistant depression and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. Primary objectives of this study were to evaluate the effect of nasal decongestant pretreatment in patients with allergic rhinitis and the impact of daily nasal corticosteroid administration by healthy subjects on nasal esketamine pharmacokinetics. METHODS: Patients with allergic rhinitis self-administered 56 mg of nasal esketamine after pretreatment with nasal oxymetazoline (0.05%) at 1 h before esketamine and without oxymetazoline pretreatment. They were exposed to grass pollen in an allergen challenge chamber to induce allergic rhinitis symptoms at approximately 2 h before each esketamine administration until 1 h after. Healthy subjects self-administered esketamine (56 mg) before and after administration for 16 consecutive days of mometasone (200 µg), with the second esketamine dose administered 1 h after the last mometasone dose. The plasma pharmacokinetics of esketamine and noresketamine were assessed after each esketamine administration. The tolerability of esketamine, including effects on dissociative and potential psychotomimetic symptoms and level of sedation and suicidal ideation and behavior, was evaluated. RESULTS: The rate of esketamine absorption was slightly greater in patients exhibiting symptoms of allergic rhinitis (decrease in median tmax from 32 min to 22 min). Increases in esketamine Cmax and AUC were also small (mean, ≤ 21%). The pharmacokinetics of esketamine was not affected by oxymetazoline or mometasone pretreatment. Esketamine was well tolerated when it was administered with or without pretreatment of oxymetazoline or mometasone. CONCLUSIONS: Patients exhibiting symptoms of rhinitis may receive nasal esketamine spray without dose adjustment. In addition, esketamine may be administered 1 h after using a nasal decongestant or corticosteroid. TRIAL REGISTRATION: The study was registered in the Clinical Trials (NCT02154334) and EudraCT (2014-000534-38) registries.

Quality of life after radio frequency ablation turbinate reduction (RFATR) among patients with rhinitis medicamentosa & withdrawal from decongestant topical spray abuse.

OBJECTIVE: Radiofrequency ablation (RFA) reliefs nasal obstruction and improves quality of life (QoL) in patients suffering from inferior turbinate hypertrophy (ITH). A substantial benefit was noted among patients suffering from Rhinitis Medicamentosa (RM), enabling ending decongestant spray abuse. Our aim was to establish the benefit from RFA with respect to QoL in patients suffering from ITH, due to the presence of RM. STUDY DESIGN: Prospective cohort study. METHODS: Prospective Cohort study, including patients suffering from ITH undergoing RFA between 9.2017 and 9.2019 in Tel Aviv Medical Center. The cohort was divided to RM and non-RM (including allergic, non-allergic) patients. The differences between the groups were compared before and after RFA, and included patients' complaints, clinical findings and QoL questionnaires (SNOT-22 & NOSE). In the RM group, the ability to wean from decongestants was also described. RESULTS: Our data demonstrated subjective QoL improvement following RFA (88.9 %, N = 90). All RM patients withdrawaled from nasal decongestant spray. NOSE questionnaire demonstrated a significant improvement in QoL after RFA in the RM group (PV = 0.025). SNOT-22 did not demonstrate significant difference in QoL between RM and the reference group (PV = 0.1). Rates of MCID>8.3 were high, without significant difference between the groups (PV = 0.2). CONCLUSION: RFA demonstrated effectiveness in achieving of withdrawal from decongestant spray in RM patients and may be a possible definitive treatment option for this group. The nasal obstruction component in SNOT-22 questionnaire & NOSE questionnaire showed improved QoL in comparison to controls. High QoL after RFA was established in our entire cohort.

The role of the topical nasal decongestant oxymetazoline as a novel therapeutic option for post-acne erythema: A split-face, double-blind, randomized, placebo-controlled trial.

Post-acne erythema (PAE) is one of the most common sequelae of acne inflammation. Unfortunately, the treatment of PAE remains challenging due to limited effective topical treatments. The objectives of this study were to evaluate the efficacy and safety of topical oxymetazoline hydrochloride (OxH) 0.05% solution for PAE. This study was a split-face, participants-and investigators-blinded, randomized, placebo-controlled trial conducted between December 2021 and March 2022 in Bangkok, Thailand. Healthy adults aged from 18 to 45 years with mild to severe PAE, according to the Clinician's Erythema Assessment (CEA), on both sides of the face were eligible. After randomization, each participant applied the OxH to one side of their face and a placebo to the contralateral face twice daily for 12 weeks. The primary outcome was PAE lesion counts. The secondary outcomes were erythema index, clinical response rate at week 12 ("clear," "almost clear," or "at least two-grade improvement" by CEA), and patient satisfaction scores. A total of 30 participants were enrolled. The OxH-treated skin showed a significantly greater mean difference (MD) reduction in PAE lesion counts than the placebo after 8 weeks of treatment (4.30, 95% confidence interval [CI] 1.42-7.18). Similarly, the MD reduction of the erythema index was higher in the OxH-treated skin from the second week (11.82, 95% CI 8.48-15.15). Additionally, the OxH-treated side also achieved a higher clinical response rate after 8 weeks of treatment (40.00% vs. 6.67%; p = 0.002) and rated higher satisfaction than those using the placebo at the end of the study (mean [standard deviation] satisfaction score 8.30 [0.18] vs 7.40 [0.18], P < 0.001). There were no serious adverse events or flares of erythema during the study. In conclusion, our study demonstrated that the topical OxH 0.05% solution was effective, well-tolerated, and safe for reducing PAE without a rebound effect. It could be a choice of PAE management. Trial Registration: Thai Clinical Trials Registry No. TCTR20211207004.

Decongestants, proton pump inhibitors, and systemic antibiotics are associated with an increased occurrence of dysbiosis.

BACKGROUND: Dysbiosis (also called dysbacteriosis) is characterized by a disruption of the microbiome, resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, and a shift in their local distribution. Dysbiosis is most commonly reported as a condition affecting the gastrointestinal tract, for example with bacterial or fungal overgrowth in the small intestine. Known causes of dysbiosis include antibiotic use, liver disease, and alcohol misuse. AIMS: To determine those variables associated with the diagnosis of dysbiosis using a national database containing data supplied by general practitioners in Germany. MATERIALS AND METHODS: Patient data for the period January 2005 to December 2018 were obtained from the Disease Analyzer database (IQVIA) based on data from 1,193 general practices in Germany. Inclusion criteria were all adult patients (≥ 18 years) with an initial diagnosis of dysbiosis documented anonymously. Data for variables such as drug treatment, other diseases etc. associated with the diagnosis were analyzed using multivariable logistic regression analyses. RESULTS: A total of 4,013 patients diagnosed with dysbiosis and a comparative control cohort of 4,013 patients without such a dysbiosis were included in the study. The mean age in both groups was ~ 50 years where 65.2% of subjects were women. Decongestants and other nasal preparations for topical use (OR: 1.45, 95% CI: 1.14 - 1.85), proton pump inhibitors (OR: 1.39; 95% CI: 1.21 - 1.61), and systemic antibiotics (OR: 1.28, 95% CI: 1.13 - 1.47) were significantly associated with an increased occurrence of dysbiosis, whereas non-steroidal antirheumatic drugs (OR: 0.78, 95% CI: 0.69 - 0.87), lipid-lowering drugs (OR: 0.76, 95% CI: 0.63 - 0.93), and ACE inhibitors (OR: 0.64, 95% CI: 0.53 - 0.77) were associated with a decreased occurrence of dysbiosis. CONCLUSION: The study provides evidence that treatment with decongestants and other nasal preparations is strongly associated with an increased occurrence of dysbiosis. Although the pathophysiology of dysbiosis is multifactorial and confounding factors cannot be ruled out, the close correlation seen may have clinical significance.

Can Sex Improve Nasal Function?-An Exploration of the Link Between Sex and Nasal Function.

OBJECTIVES: This study was conducted to examine the impact of sexual activity on nasal breathing and compare such effect to that of a nasal decongestant. METHODS: We evaluated nasal breathing at 5 different times: (1) before sexual activity (baseline), (2) immediately after sexual activity, (3) 30 minutes, (4) 1 hour (5), and 3 hours after sexual climax. Same measurements were taken on the second day following application of nasal decongestant spray. For evaluation of nasal breathing, we used a visual analogue scale (VAS). Additionally, we used a portable rhinometric device to measure resistance and nasal flow. RESULTS: Nasal breathing improved significantly after sexual intercourse with climax to the same degree as after application of nasal decongestant for up to 60 minutes, as measured subjectively with the VAS (sex -3.6, P < .001; spray -3.2, P < .001). This was confirmed in the objective rhinometric data as mean nasal flow (mL/s) increased while resistance decreased immediately (flow sex +214, P < .001; flow spray +235, P < .001), 30 (flow sex +249, P < .001; flow spray +287, P < .001), and 60 minutes (flow sex +180, P < .001; flow spray +287, P < .001) post-intervention. Nasal breathing was back to the baseline level after 3 hours following sexual intercourse, while it continued to be improved for longer after application of nasal decongestant. Only participants having nasal obstruction (Nasal Obstruction Symptom Evaluation score >30) showed nasal function improvement after sex. CONCLUSIONS: Sexual intercourse with climax can improve nasal breathing to the same degree as application of nasal decongestant for up to 60 minutes in patients having nasal obstruction.

Rhinomanometry with and without decongestant used to select children for adenoidectomy: a cohort study.

OBJECTIVE: Adenoid hypertrophy may coexist, and often does, with rhinitis. Therefore, in some cases, adenoidectomy alone, despite the fact that it reduces nasal resistance, may be insufficient to restore nasal breathing. Juliusson et al. suggested using rhinomanometry with and without nasal decongestant as a method for selecting patients for adenoidectomy. In this study, we aim to assess whether the decongestant test, when using normative data, is useful to select children for adenoidectomy. METHODS: Children between 4 and 15 years old undergoing adenoidectomy were selected from two tertiary referral university hospitals. Participants underwent anterior active rhinomanometry with and without nasal decongestant before and after surgery. Parents fill in the sinus and nasal quality-of-life survey (SN5). RESULTS: 47 participants were included, and mean age 6.5 ± 2.15. 2 cohorts were defined according to the result of the nasal decongestant test (> 40% improvement in nasal resistance or not). There is a statistically significant difference between groups, with a higher improvement in nasal resistance and airflow after adenoidectomy in the group with less than 40% improvement in nasal resistance. CONCLUSIONS: In conclusion, this study supports the use of the decongestant test with rhinomanometry to select children for adenoidectomy; especially as it has proven to be a simple technique, harmless, fast, and easily performed on collaborative children.

The Indispensable Nasal Decongestant: Patients' Views and Perspectives on Nasal Decongestant Overuse.

BACKGROUND: Rhinitis medicamentosa (RM) is a type of nonallergic rhinitis caused by prolonged use of nasal decongestants (NDs). Although it is a preventable phenotype of rhinitis, little is known about patients dealing with this condition. OBJECTIVE: To gain a better understanding of patients' views and experiences of ND overuse, and potential facilitators and barriers to discontinue the overuse. METHODS: We performed a qualitative study using in-depth semistructured interviews with 22 patients who have been using an ND on an almost daily basis for at least 6 months. The interviews were conducted face-to-face, audio-recorded, and transcribed verbatim. Data analysis followed the grounded theory approach. RESULTS: Interviewees described the large impact of nasal congestion on their daily lives. Despite efforts to try other treatment options, the ND was considered the only effective aid to resolve the troublesome symptom. Most participants were aware that the prolonged use was problematic, sometimes leading to hiding behavior in order to avoid criticism by others including their health professionals. Many participants expressed a strong will to discontinue. However, multiple barriers to withdrawal were identified including fear of surgery or the impact of withdrawal on sleep, lack of good alternatives, and negative experiences with past withdrawal attempts. Patients thus face a dilemma in which the barriers to withdrawal currently outweigh the possible benefits. CONCLUSION: The use of NDs is considered indispensable by many chronic users. The facilitators and barriers identified in this study provide opportunities to reduce the use of NDs and the prevalence of RM in the future.

Use of xylometazoline in hospitalised infants: is it safe? A retrospective cohort study.

OBJECTIVE: When infants suffer from nasal congestion, xylometazoline spray or drops can be effective to facilitate breathing and drinking. However, case reports on side effects have resulted in international warnings regarding use of xylometazoline in infants. Nevertheless, the incidence of these side effects in hospitalised infants is unknown. DESIGN: Retrospective cohort study. SETTING: Teaching hospital between 2017 and 2021. PATIENTS: Infants under 2 years of age. EXPOSURE: Receiving either saline-only (unlimited frequency, concentration 0.9%) or in combination with xylometazoline (maximum three times daily, concentration 0.025%). MAIN OUTCOME MEASURES: Predefined potential side effects (events), including among others apnoea, nausea, bradycardia, cyanosis and nosebleeds, were extracted from patient records, and the probability to be caused by saline only or xylometazoline-saline was determined using the ADR Probability Scale. RESULTS: We included 898 admitted children during 1285 treatment episodes who received saline with or without xylometazoline. 26 events occurred in the saline-only group (incidence 20.0/100 treatment episodes), and 117 events occurred in the xylometazoline saline group (incidence of 10.5/100 treatment episodes), which was significantly lower (OR 0.47 95% CI 0.29 to 0.75, p=0.002). No definite linked or life-threatening events were found. Three nosebleeds had a probable link to the use of xylometazoline-saline, and all other events could only possibly be linked to saline-only or xylometazoline saline use. The incidence of all events was higher in the saline-only group as compared with the xylometazoline saline group, except nausea, which had a similar occurrence (p=0.65). Results were very similar across (gestational) age groups, gender and reasons for admission. CONCLUSION: The use of low-dose xylometazoline seems to be safe in hospitalised infants.

Development of an intranasal formulation containing indomethacin and xylometazoline for rhinosinusitis treatment.

OBJECTIVE: Use of the nasal route of drug administration dates back many years and is used both to achieve topical treatments and to allow systemic absorption. The objective was to develop a formulation with novel features which enhance prolonged contact with the nasal and sinusal lining, since this should increase any therapeutic benefit. The anti-inflammatory drug selected was indomethacin, which was combined with xylometazoline, an effective nasal decongestant agent. MATERIALS AND METHODS: 28 Sprague-Dawley rats were used. They were then allocated at random to one of the four groups of equal size. All rats received a nasal application of 50mL of the platelet-activating factor solution at a concentration of 16 µg/mL and had induced rhinosinusitis. Indomethacin or xylometazoline HCl or both were dissolved in the oily phase of the solution and then a magnetic stirrer was used to homogenize the solution for 60 min at room temperature. All the O/W solutions exhibited stability and remained at neutral pH for the entire duration of the experiment. The only intervention was application of inactive 0.9% saline in group 1. The intervention was nasal application of xylometazoline and indomethacin in the combined formulation in group. The intervention was nasal application of xylometazoline only in group 3. The intervention was nasal application of indomethacin only in group 4. RESULTS: For the animals in group 1 (the controls), the mucosa had sustained a significant level of damage and the vessels were highly congested. Inflammatory cells were extensively infiltrating the mucosa. (Figure 1 - A1, 2, 3). In group 2, by contrast, the vessels were hardly congested and there were very few infiltrates. The epithelium appeared completely intact (Figure 1 - B1, 2, 3). Furthermore, when groups 1 and 2 were compared in terms of congested vessels, inflammatory cellular infiltrates and injury to the epithelium, the differences reached statistical significance, with p-values of <0.01, >0.001 and <0.001, respectively. Comparison of groups 2 and 4 with the control group also revealed statistically significant differences in terms of cellular infiltrates (p<0.001) and damage to the epithelium (p<0.001). For the degree of congestion of the vessels, however, the difference between groups was not at the level of statistical significance (p<0.071). Groups 3 and 4 differed at a statistically significant level in terms of degree of congested vessels, cellular infiltrates, and damage to the epithelium (p<0.025 and p<0.001). The sections from rats in groups 2 and 3 had a lower degree of congested vessels, which may be due to the actions of xylometazoline. CONCLUSIONS: In the future, topically applied intranasal NSAIDs will be valuable formulations. Innovative types of formulation, such as those demonstrating thixotropic behavior, permit the agent to remain in prolonged contact with the nasal and sinusal lining. Alongside increased efficacy, these preparations will also improve the side effect profile of NSAIDs, largely eliminating systemic effects.