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.

Safety and Performance of Narhinel 0.9% Sodium Chloride Monodose and Otrisal 0.74% Sodium Chloride Monodose Nasal Saline Solutions and Nasal Aspirators in Real-World Settings: Postmarket Clinical Follow-up Study Results.

Background: Blocked or stuffy nose is a common and bothersome symptom of colds, particularly for young children who are unable to clear their noses on their own. Nasal saline solutions and nasal aspirators are designed to gently cleanse and remove blocking nasal secretions. Objective: To assess the safety and performance of 2 monodose isotonic saline solutions (Narhinel 0.9% and Otrisal 0.74% sodium chloride; GSK Consumer Healthcare SARL, a Haleon company, Nyon, Switzerland) and 2 nasal aspirators with disposable hard- and soft-nozzle refills used as a standalone or combination treatment. Methods: We conducted 2 observational, online questionnaire-based, postmarket clinical follow-up studies in Europeans who had used any of the devices ≥1 time in the past 6 months. Coprimary objectives were to confirm the safety and performance of the saline solutions (Narhinel and Otrisal, Study 1) and nasal aspirators (with hard- and soft-nozzle refills, Study 2). Safety was assessed via the proportion of patients reporting adverse events and/or device malfunctions while using the devices within the previous 6 months, and performance was assessed by satisfaction rated on a 5-point scale, with "satisfied" and "very satisfied" being the highest performance ratings. Results: A total of 1136 (Study 1) and 1237 (Study 2) questionnaires were initiated by volunteer participants. Less than 2% of participants reported adverse events for any evaluated product in the previous 6 months. Most participants were "satisfied" or "very satisfied" with the devices for their intended use, with 78% to 91% of participants in the Narhinel arm, 73%-94% in the Otrisal arm, 71% to 95% in the soft-nozzle arm, and 71% to 80% in the hard-nozzle arm giving these ratings. Conclusions: These data support the safety and performance of 2 monodose saline solutions (Narhinel and Otrisal) for nasal cleansing, nasal moisturization, and/or loosening nasal secretions, and of nasal aspirators (with hard- and soft-nozzle refills) for clearing a blocked nose and removing nasal secretions.

Pain characteristics and biomarkers in treatment approaches for osteoarthritis pain.

Osteoarthritis (OA) is a progressive disease and OA pain intensity is related to ongoing pathophysiological changes. However, OA pain is complex and multimodal; its characteristics, including severity, localization and the stimuli that elicit it, can change as the disease progresses and differ greatly among patients. Understanding mechanisms underlying specific pain characteristics may help guide clinicians in choosing appropriate treatments, targeting treatments to those patients most likely to benefit. Associations have been demonstrated between biomarkers and some characteristics of OA pain, and to processes linked to the shift in pain characteristics over the course of OA. This article examines how understanding OA pain characteristics and their relation to the disease process could inform treatment choice when applying well-established treatment guidelines.

Penetration of topical diclofenac into synovial tissue and fluid of osteoarthritic knees: a multicenter, randomized, placebo-controlled, pharmacokinetic study.

BACKGROUND: Topical diclofenac, a nonsteroidal anti-inflammatory drug, has proven efficacy and safety in the management of osteoarthritis pain. We investigated penetration of topical diclofenac into knee synovial tissue and fluid (primary objective) and evaluated relative exposure in the knee versus plasma (secondary objective). METHODS: In this phase I, double-blind, multicenter study, patients scheduled for arthroplasty for end-stage knee osteoarthritis were randomly assigned 2:1 to 4 g diclofenac diethylamine 2.32% w/w gel (92.8 mg diclofenac diethylamine, equivalent to 74.4 mg diclofenac, per application) or placebo gel, applied to the affected knee by a trained nurse/designee every 12 h for 7 days before surgery. Diclofenac concentrations were measured in synovial tissue, synovial fluid and plasma from samples obtained during surgery ⩾12 h after last application. Treatment-emergent adverse events (TEAEs) were evaluated. RESULTS: Evaluable synovial tissue or fluid samples were obtained from 45 (diclofenac n = 29; placebo n = 16) of 47 patients. All diclofenac-treated participants had measurable diclofenac concentrations in synovial tissue [geometric mean 1.57 (95% confidence interval (CI) 1.12, 2.20) ng/g] and fluid [geometric mean 2.27 (95% CI 1.87, 2.76) ng/ml] ⩾12 h after the last dose. Geometric mean (95% CI) ratio of diclofenac in synovial tissue:plasma was 0.32 (0.23, 0.45) and in synovial fluid:plasma was 0.46 (0.40, 0.54). TEAE rates were similar for diclofenac (55.2%) and placebo (58.8%); none were treatment related. CONCLUSIONS: Topical diclofenac diethylamine 2.32% w/w gel penetrated into the osteoarthritic knee after repeated application and remained detectable in synovial tissue and fluid at the end of the final 12 h dosing cycle.

Combined analysis of 3 cross-sectional surveys of pain in 14 countries in Europe, the Americas, Australia, and Asia: impact on physical and emotional aspects and quality of life.

Background and aims Recognition of the biopsychosocial aspects of pain is important for a true understanding of the burden of pain and the necessity of pain management. Biopsychosocial aspects of pain may differ between countries and cultures. Market research methods can be well suited and effective for assessing patient perspectives of pain and biopsychosocial differences. We conducted and combined 3 cross-sectional, international surveys to document the impact of pain on physical and emotional aspects of life, as well as quality of life (QOL). Methods Online panelists from 24 countries took part in our surveys in 2014, 2016, and 2017. Fourteen countries (Australia, Brazil, Canada, China, Germany, Italy, Japan, Poland, Russia, United Kingdom, United States, Mexico, Sweden, Saudi Arabia) contributed data in all 3 surveys and comprise the analysis population. A Global Pain Index (GPI) was constructed using 8 questions in 3 categories: Physical (frequency, duration, intensity of pain), Emotional (anxiety, impact on self-esteem, happiness), and Impact on QOL and ability to enjoy life. Each item was scored as the percentage of respondents meeting a prespecified threshold indicative of a substantial pain impact. Scores for the items within each category were averaged to obtain a category score, category scores were averaged to obtain a total score for each survey, and total scores from each survey were averaged to obtain a final combined score. Scores were assessed for the overall population, by individual countries, by age and gender, and by self-identified pain-treatment status (treat immediately, wait, never treat). Results Of the 50,952 adult respondents, 28,861 (56.6%) had ever experienced musculoskeletal pain; 50% of those with pain had pain with a multifaceted impact based on the GPI (Physical: 51%; Emotional: 40%; QOL Impact: 59%). Russia (57%) and Poland (56%) had the highest scores; Mexico (46%), Germany (47%), and Japan (47%) had the lowest. GPI score was higher in women (52%) than men (48%), and initially increased with age through age 54 (18‒24 years: 45%; 25‒34 years: 52%; 35‒44 years: 53%; 45‒54 years: 54%), after which it decreased again (55‒64 years: 51%; ≥65 years: 45%). A majority (65%) of respondents wait to treat their pain, whereas 21% treat their pain immediately and 14% never treat pain. The most common reason for waiting (asked in survey 3 only) was to avoid taking medication. Conclusions In this combined analysis of 3 international surveys using a novel biopsychosocial pain assessment tool, pain had a substantial impact on ~50% of respondents' lives, spanning physical (51%), emotional (40%), and QOL effects (59%). Despite the substantial impact, a majority of patients tried to avoid treating their pain. Implications Clinicians should take a biopsychosocial approach to pain by asking patients not only about the presence and severity of pain, but the extent to which it affects various aspects of their lives and daily functioning. Patients may also need education about the efficacy and safety of available treatments for self-management of pain. The GPI may be a useful new tool for future studies of the biopsychosocial effects of pain in large populations.

Topical Diclofenac, an Efficacious Treatment for Osteoarthritis: A Narrative Review.

Multiple head-to-head trials have demonstrated that topical nonsteroidal anti-inflammatory drugs (NSAIDs), including topical diclofenac, provide at least equivalent analgesia, improvement in physical function, and reduction of stiffness compared with oral NSAIDs in osteoarthritis and have fewer systemic adverse events. While efficacy of topical diclofenac in osteoarthritis is well established, understanding of the time to onset of action, duration of effect, and the minimum effective concentration is limited. Factors likely to influence these parameters include drug penetration and localization. Diclofenac concentrations in the joint tissues are likely to be more relevant than plasma concentrations. However, although diclofenac penetrates and is retained in these "effect compartments" at the site of inflammation and drug activity, no specific minimum effective concentration of diclofenac in plasma or synovial tissue has been identified. Recent evidence suggests that a reduction in inflammatory markers may be a better predictor of efficacy than plasma concentrations. This narrative review explores existing evidence in these areas and identifies the gaps where further research is needed. Based on our findings, topical NSAIDs such as diclofenac should be considered as a guideline-supported, generally well-tolerated, and effective first-line treatment option for knee and hand OA, especially for older patients and those who have comorbid conditions and/or risk factors for various systemic (gastrointestinal, hepatic, renal, or cardiovascular) adverse events associated with oral NSAIDs, particularly at high doses and with long-term use.

Nonprescription drugs recommended in guidelines for common pain conditions.

Evidence-based pain guidelines allow recommendation of nonprescription analgesics to patients, facilitating self-care. We researched clinical practice guidelines for common conditions on websites of pain associations, societies, health institutions and organizations, PubMed, ProQuest, Embase, Google Scholar until April 2019. We wanted to determine whether there is a consensus between guidelines. From 114 identified guidelines, migraine (27) and osteoarthritis (26) have been published most around the world, while dysmenorrhea (14) is mainly discussed in developing countries. Specific recommendations to pregnant women, children and older people predominantly come from the UK and USA. We found that acetaminophen and oral nonsteroidal anti-inflammatory drugs (NSAIDs) represent first-line management across all pain conditions in adults and children. In osteoarthritis, topical NSAIDs should be considered before oral NSAIDs. This knowledge might persuade patients that using these drugs first could enable fast and effective pain relief.

Comparison of gait, functional activities, and patient-reported outcome measures in patients with knee osteoarthritis and healthy adults using 3D motion analysis and activity monitoring: an exploratory case-control analysis.

OBJECTIVE: To examine functional performance differences using kinematic and kinetic analysis between participants with and without knee osteoarthritis (OA) to determine which outcomes best characterize persons with and without knee OA. METHODS: Participants with unilateral moderate knee OA (Kellgren-Lawrence grades 2 or 3) and controls without knee pain were matched for age, gender, and body mass index. Primary outcomes included temporal parameters, joint rotations and moments, and ground reaction forces assessed via 3D motion capture during walking and ascending/descending stairs. Secondary outcomes included timed functional activities (sit to stand; tying shoelaces), 48 hrs lower limb activity monitoring, and patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, European Quality of Life-5 Dimensions). RESULTS: Eight matched pairs were analyzed. Compared with controls, OA participants exhibited significant reductions in peak frontal hip and sagittal knee moments, and decreased peak anterior ground reaction force with the affected limb while walking. Ascending stairs, OA participants had slower speed, fewer strides per minute, longer cycle and stance times, and increased trunk range of motion (ROM) in assessments of both limbs; longer swing time and reduced ankle ROM in the affected limb; and increased knee frontal ROM in the unaffected limb. Descending stairs, OA participants had fewer strides per minute and decreased trunk transverse ROM in assessments of both limbs; increased knee frontal ROM in the affected limb; and longer strides, shorter stance and cycle times, increased trunk sagittal and decreased knee transverse ROMs in the unaffected limbs vs controls. Compared with controls, OA participants had slower walking cadence (120-130 vs 100-110 steps/min, respectively), took significantly longer on timed functional measures, and had significantly worse scores in patient-reported outcomes. CONCLUSION: Several objectives and patient-reported measures examined in this study could potentially be considered as outcomes in pharmacologic or physical therapy OA trials.

A Dietary Assessment App for Hospitalized Patients at Nutritional Risk: Development and Evaluation of the MyFood App.

BACKGROUND: Disease-related malnutrition is a common challenge among hospitalized patients. There seems to be a lack of an effective system to follow-up nutritional monitoring and treatment of patients at nutritional risk after risk assessment. We identify a need for a more standardized system to prevent and treat disease-related malnutrition. OBJECTIVE: We aimed to develop a dietary assessment app for tablets for use in a hospital setting and to evaluate the app's ability to measure individual intake of energy, protein, liquid, and food and beverage items among hospitalized patients for two days. We also aimed to measure patients' experiences using the app. METHODS: We have developed the MyFood app, which consists of three modules: 1) collection of information about the patient, 2) dietary assessment function, and 3) evaluation of recorded intake compared to individual needs. We used observations from digital photography of the meals, combined with partial weighing of the meal components, as a reference method to evaluate the app's dietary assessment system for two days. Differences in the intake estimations of energy, protein, liquid, and food and beverage items between MyFood and the photograph method were analyzed on both group and individual level. RESULTS: Thirty-two patients hospitalized at Oslo University Hospital were included in the study. The data collection period ran from March to May 2017. About half of the patients had ≥90% agreement between MyFood and the photograph method for energy, protein, and liquid intake on both recording days. Dinner was the meal with the lowest percent agreement between methods. MyFood overestimated patients' intake of bread and cereals and underestimated fruit consumption. Agreement between methods increased from day 1 to day 2 for bread and cereals, spreads, egg, yogurt, soup, hot dishes, and desserts. Ninety percent of participants reported that MyFood was easy to use, and 97% found the app easy to navigate. CONCLUSIONS: We developed the MyFood app as a tool to monitor dietary intake among hospitalized patients at nutritional risk. The recorded intake of energy, protein, and liquid using MyFood showed good agreement with the photograph method for the majority of participants. The app's ability to estimate intake within food groups was good, except for bread and cereals which were overestimated and fruits which were underestimated. The app was well accepted among study participants and has the potential to be a dietary assessment tool for use among patients in clinical practice.

Skin penetration and tissue permeation after topical administration of diclofenac.

OBJECTIVE: Topical delivery of drugs is an alternative to oral administration, often with similar efficacy but potentially a more favorable tolerability profile. However, topical formulations need to be able to penetrate the skin and permeate to the target areas in quantities sufficient to exert a therapeutic effect. Many factors can affect this process, including the physicochemical properties of the drug, the formulation used, and the site and mode of application. It is believed that measurement of drug concentrations at the sites of action may be an indicator of their likely efficacy. This review addresses these issues, with reference to topically administered diclofenac in osteoarthritis. METHODS: Articles relevant to this review were identified after a systematic search of Medline and Embase, using the key words "diclofenac", "topical administration" and "osteoarthritis" in the search strategy. RESULTS: The sparse data available indicate that topical diclofenac can penetrate and permeate to deeper tissues, with a lower plasma to tissue ratio than oral diclofenac. The tissue diclofenac levels after topical delivery are sustained over time (at least several hours). However, there is not enough data to establish how diclofenac levels in the joint compare with IC50 levels (50% of the maximum inhibition of prostaglandin synthesis) established following oral administration. CONCLUSIONS: After topical application, diclofenac can penetrate the skin and permeate to deeper tissues, where it reaches a concentration that appears to be sufficient to exert a therapeutic effect. More robust methods are required for in vivo characterization to better estimate the clinical efficacy of topically applied drugs.

Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies.

BACKGROUND: Most patients with episodic tension-type headache treat headache episodes with over-the-counter medication. Combination analgesics containing caffeine may be more effective and as well tolerated as monotherapy. The aim of this study was to evaluate the efficacy of the combination of acetylsalicylic acid, acetaminophen (paracetamol) and caffeine in episodic tension-type headache using recently recommended endpoints. METHODS: Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs. acetaminophen or placebo were pooled. Analysis populations were 'all headache episodes' and those with 'severe pain at baseline'. Post-hoc defined primary endpoint: headache episodes pain-free at 2 h. Secondary endpoints: headache episodes pain-free at 1 h, headache response at 2 h (mild or no pain), degree of interference with daily activities. RESULTS: 6,861 headache episodes were treated, including 2,215 severe headache episodes. The proportion of headache episodes pain-free at 2 h was significantly higher with the triple combination (28.5%) vs. acetaminophen (21.0%) and placebo (18.0%) (p < 0.0001), and similarly for those severe at baseline (20.2% vs. 12.1% and 10.8%; p ≤ 0.0003). A similar pattern of superiority was observed for secondary endpoints. The triple combination was generally well tolerated. CONCLUSIONS: The combination of acetylsalicylic acid, acetaminophen and caffeine is effective and well tolerated in episodic tension-type headache, and significantly superior to acetaminophen with regard to being pain-free at 2 h, headache response at 2 h and ability to return to daily activities, even in those with pain rated severe at baseline.

Results of a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study comparing the fixed combination of acetaminophen, acetylsalicylic acid, and caffeine with ibuprofen for acute treatment of patients with severe migraine.

INTRODUCTION: In a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study (n = 1555), a fixed combination of acetaminophen 500 mg, acetylsalicylic acid 500 mg, and caffeine 130 mg (AAC) was compared with ibuprofen 400 mg (IB) and placebo (PLA) for acute treatment of migraine. SUBJECTS AND METHODS: An exploratory post-hoc analysis compared AAC with IB and PLA in the subset of patients with severe pain at baseline (n = 660). RESULTS: At most time points, AAC and IB relieved the pain and associated symptoms of severe migraine significantly better than PLA (p ≤ 0.05). AAC was significantly superior to IB for pain relief at 45 minutes and at one, two, three, and four hours postdose (p < 0.04); pain intensity difference from one hour through three hours (p < 0.05); headache response at two hours (p = 0.04); functional disability reduced to little or none at three hours (p = 0.013); freedom from phonophobia at three hours (p = 0.04) and photophobia at 15 minutes postdose (p = 0.03); and use of rescue medication (p = 0.018). AAC patients also reported meaningful pain relief 16 minutes faster than IB patients (132 minutes vs 148 minutes, p = 0.026). CONCLUSIONS: In patients with severe baseline migraine pain, AAC and IB are significantly more effective than PLA, and AAC provides significantly faster and more effective pain relief than IB.