Objectives: We set out to determine the psychometric validation of a disease‐specific health related quality of life instrument for use in chronic rhinosinusitis, the 22 item Sinonasal Outcome Test ...(SNOT‐22), a modification of a pre‐existing instrument, the SNOT‐20.
Design, setting and participants: The National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis was a prospective cohort study collecting data on 3128 adult patients undergoing sinonasal surgery in 87 NHS hospitals in England and Wales. Data were collected preoperatively and at 3 months after surgery, and analysed to determine validity of the SNOT‐22. Test–retest reliability was assessed in a separate cohort of patients in a single centre.
Main outcome measures: The SNOT‐22, a derivative of the SNOT‐20 was the main outcome measure. Patients were also asked to report whether they felt better, the same or worse following surgery. To evaluate the SNOT‐22, the internal consistency, responsiveness, known group differences and validity were analysed.
Results: Preoperative SNOT‐22 scores were completed by 2803 patients. 3‐month postoperative SNOT‐22 scores were available for 2284 patients of all patients who completed a preoperative form (81.5% response rate). The Cronbach’s alpha scores for the SNOT‐22 were 0.91 indicating high internal consistency. The test–retest reliability coefficient was 0.93, indicating high reliability of repeated measures. The SNOT‐22 was able to discriminate between patients known to suffer with chronic rhinosinusitis and a group of healthy controls (P < 0.0001, t = 85.3). It was also able to identify statistically significant differences in sub‐groups of patients with chronic rhinosinusitis. There was a statistically significant (P < 0.0001, t = 39.94) decrease in patient reported SNOT‐22 scores at 3 months. At 3 months the overall effect size in all patients was 0.81, which is considered large. We found the minimally important difference that is the smallest change in SNOT‐22 score that can be detected by a patient, to be 8.9 points.
Conclusions: We have found the SNOT‐22 to be valid and easy to use. It can be used to facilitate routine clinical practice to highlight the impact of chronic rhinosinusitis on the patient’s quality of life, and may also be used to measure the outcome of surgical intervention. The minimally important difference allows us to interpret scores in a clinical context, and may help to improve patient selection for surgery.
Background
It is imperative to develop markers for risk stratification and detection of cardiometabolic comorbidities in children with obesity. The adipokines leptin and adiponectin are both involved ...in fat mass regulation and the development of obesity‐related disorders; furthermore, their ratio (leptin/adiponectin ratio) is suggested to be associated with insulin resistance and cardiometabolic risk.
Objective
To evaluate associations between fasting serum concentrations of the adipokines (total leptin and adiponectin as well as the L/A ratio) and cardiometabolic comorbidities in children with overweight/obesity.
Methods
A total of 2258 children with overweight/obesity or normal weight aged 6 to 18 years were studied. Differences in anthropometrics and adipokine concentrations were tested using Wilcoxon rank‐sum test. Associations between the adipokines and cardiometabolic risk were tested using Spearman's correlation and logistic regression, adjusted for age and body mass index SD score (BMI‐SDS).
Results
Compared to normal weight children; children with overweight/obesity exhibited higher leptin concentrations, lower adiponectin concentrations, and higher L/A ratios. After adjusting for age and degree of obesity, girls with overweight/obesity in the upper quartile range for the L/A ratio, when compared with girls in the lower quartile range, were more likely to have insulin resistance (odds ratio OR: 7.78 95% confidence interval CI, 3.78‐16.65), dysglycemia (OR: 3.08 95% CI, 1.35‐7.31), and dyslipidemia (OR: 2.53 95% CI, 1.18‐5.59); while boys were more likely to have insulin resistance (OR: 4.45 95% CI, 2.03‐10.10).
Conclusions
Independent of the degree of obesity, leptin, adiponectin, and the L/A ratio were associated with insulin resistance and other cardiometabolic comorbidities in children with overweight/obesity, but the L/A ratio exhibited stronger associations than the respective adipokines.
State‐of‐the‐art documents like ARIA and EPOS provide clinicians with evidence‐based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently ...available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so‐called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline‐directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment‐related, diagnosis‐related and/or patient‐related factors. Treatment‐related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom‐oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient‐related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain.
To cite this article: Videler WJ, Badia L, Harvey RJ, Gane S, Georgalas C, van der Meulen FW, Menger DJ, Lehtonen MT, Toppila‐Salmi SK, Vento SI, Hytönen M, Hellings PW, Kalogjera L, Lund VJ, ...Scadding G, Mullol J, Fokkens WJ. Lack of Efficacy of long‐term, low‐dose azithromycin in chronic rhinosinusitis: a randomized controlled trial. Allergy 2011; 66: 1457–1468.
Background: In persistent chronic rhinosinusitis (CRS), conventional treatment is often insufficient. Long‐term, low‐dose administration of macrolides has been suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis) study is a randomized placebo‐controlled trial evaluating the efficacy of azithromycin (AZM) in CRS.
Methods: We describe a group of patients with recalcitrant CRS with and without nasal polyps unresponsive to optimal medical and (in 92% also) surgical treatment. Patients were treated with AZM or placebo. AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per week for the next 11 weeks. Patients were monitored until 3 months post‐therapy. The assessments included Sino‐Nasal Outcome Test‐22 (SNOT‐22), a Patient Response Rating Scale, Visual Analogue Scale (VAS), Short Form‐36 (SF‐36), rigid nasal endoscopy, peak nasal inspiratory flow (PNIF), Sniffin’ Sticks smell tests and endoscopically guided middle meatus cultures.
Results: Sixty patients with a median age of 49 years were included. Fifty per cent had asthma and 58% had undergone revision sinus surgery. In the SNOT‐22, Patient Response Rating Scale, VAS scores and SF‐36, no significant difference between the AZM and the placebo groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and microbiology showed no relevant significant differences between the groups either.
Conclusion: At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under‐dosage of AZM and under‐powering of the study. Therefore, more research is urgently required.
Patients with chronic rhinosinusitis refractory to medical management undergo elective surgery. The time from initial diagnosis to surgery varies considerably. The impact of this delay on surgical ...success has never previously been evaluated.
First-time patients within the National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis were grouped based on time to surgery: 1) Early cohort: %lt; 12 months; 2) Mid cohort: 12-60 months; and 3) Late cohort: > 60 months. Co-morbidities and preoperative CT scores were analysed for all patients.
The 22-item Sino-Nasal Outcome Test scores (SNOT-22) were collected at 0, 3, 12 and 60-months. Absolute and relative SNOT-22 changes from baseline were evaluated.
Asthma and allergies were significantly more prevalent in the Late versus the Early and Mid-cohorts. In addition, patients in the Late cohort had greater symptom burden on the SNOT-22 and more extensive preoperative radiographic disease as determined by Lund-Mackay (LM) scores. SNOT-22 scores demonstrated greater percentage improvements in the Early versus the Mid- and Late cohorts, at all time points after surgery. At 12 and 60 months after surgery, significantly more patients in the Early group achieved a clinically important change in SNOT-22 scores compared with the other groups. These differences were maintained when cohorts were matched for preoperative co-morbidities.
Patients with asthma and/or allergies are more likely to experience delayed surgical intervention versus other patients. Overall, patients with delayed surgery reported less improvement in SNOT-22 scores than patients treated at earlier time points, regardless of co-morbid status. Delaying surgical intervention may worsen long term clinical outcomes.
Tumor hypoxia levels range from mild to severe and have different biological and therapeutical consequences but are not easily assessable in patients. Here we present a method based on diagnostic ...dynamic contrast enhanced (DCE) MRI that reflects a continuous range of hypoxia levels in patients with tumors of cervical cancer. Hypoxia images were generated using an established approach based on pixel-wise combination of DCE-MRI parameters
and
, representing oxygen consumption and supply, respectively. Using two tumor models, an algorithm to retrieve surrogate measures of hypoxia levels from the images was developed and validated by comparing the MRI-defined levels with hypoxia levels reflected in pimonidazole-stained histologic sections. An additional indicator of hypoxia levels in patient tumors was established on the basis of expression of nine hypoxia-responsive genes; a strong correlation was found between these indicator values and MRI-defined hypoxia levels in 63 patients. Chemoradiotherapy outcome of 74 patients was most strongly predicted by moderate hypoxia levels, whereas more severe or milder levels were less predictive. By combining gene expression profiles and MRI-defined hypoxia levels in cancer hallmark analysis, we identified a distribution of levels associated with each hallmark; oxidative phosphorylation and G
-M checkpoint were associated with moderate hypoxia, epithelial-to-mesenchymal transition, and inflammatory responses with significantly more severe levels. At the mildest levels, IFN response hallmarks together with HIF1A protein expression by IHC appeared significant. Thus, our method visualizes the distribution of hypoxia levels within patient tumors and has potential to distinguish levels of different prognostic and biological significance. SIGNIFICANCE: These findings present an approach to image a continuous range of hypoxia levels in tumors and demonstrate the combination of imaging with molecular data to better understand the biology behind these different levels.
The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS), and the European Medical Association (EMA) organized, on October 14, 2015, a symposium in the ...European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli, and with active participation of the EU Commissioner for Health and Food Safety Vytenis Andriukaitis, MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA), and the Respiratory Effectiveness Group (REG). The socioeconomic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic noncommunicable diseases in the EU; 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision medicine represents a novel approach, embracing four key features: personalized care based on molecular, immunologic, and functional endotyping of the disease, with participation of the patient in the decision‐making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of precision medicine into clinical practice may help to achieve the arrest of the epidemic of allergies and chronic airways diseases. Participants underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment, and cost‐effective treatment strategies.
Climate change will lead to higher temperatures, increased precipitation and runoff, as well as more intense and frequent extreme weather events in Norway. More extreme rainfall and increased runoff ...are historically associated with higher concentrations of indicator bacteria, colour and turbidity in raw water of Norwegian waterworks. Regional information about the risk for drinking water deterioration by the end of the century is essential for evaluating potential treatment capacity upgrades at the waterworks. We combined locally downscaled future climate scenarios with historical associations between weather/runoff and water quality from a wide spread of waterworks in Norway. With continued climate change, we estimate higher concentrations of water quality indicators of raw water by the end of the century. The water quality is estimated to deteriorate mainly due to the projected increase in rainfall, and mainly in the Western and Northern parts of Norway. While large waterworks seem to be able to adapt to future conditions, the degradation of raw water quality may cause future challenges for the treatment processes at smaller waterworks. Combining these results with further studies of treatment effects and microbial risk assessments is needed to ensure sufficient treatment capacities of the raw water in the future.
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