Highlights • Mast cells are strategically located at major body surfaces and along blood vessels. • They play a key role as first line defense against bacterial, viral and parasitic infections. • ...Mast cells display a wide set of receptors which recognize and internalize pathogens. • Activation of mast cell receptors induces release of mediators that promote inflammation and recruitment of cells of innate immunity. • Mast cells shape adaptive immunity through soluble mediators and cognate interactions with T, B and Treg cells.
Background
Validated combined symptom‐medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real‐life data from the MASK‐air® app to ...generate and validate hypothesis‐ and data‐driven CSMSs.
Methods
We used MASK‐air® data to assess the concurrent validity, test‐retest reliability and responsiveness of one hypothesis‐driven CSMS (modified CSMS: mCSMS), one mixed hypothesis‐ and data‐driven score (mixed score), and several data‐driven CSMSs. The latter were generated with MASK‐air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale VAS of work of MASK‐air®, and Work Productivity and Activity Impairment: Allergy Specific WPAI‐AS), (ii) quality‐of‐life (EQ‐5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test CARAT).
Results
We assessed 317,176 days of MASK‐air® use from 17,780 users aged 16‐90 years, in 25 countries. The mCSMS and the factor analyses‐based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate‐to‐strong correlations with the tested comparators, high test‐retest reliability and moderate‐to‐large responsiveness. Among data‐driven CSMSs, a better performance was observed for cluster analyses‐based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC‐ROC = 0.904) and for the mixed CSMS (AUC‐ROC = 0.820).
Conclusion
The mixed CSMS and the cluster‐based CSMSs presented medium‐high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.
This study assessed 317,176 days of MASK‐air® (Mobile Airways Sentinel NetworK) use from 17,780 users aged 16‐90 years, in 25 countries. Real‐world data obtained with the MASK‐air® app were used to develop combined symptom‐medication scores to assess the daily control of allergic rhinitis. These scores had medium‐high validity, reliability and accuracy, rendering them as candidates for clinical practice, and for primary endpoints in future rhinitis trials and observational studies.
Recurrent angioedema (AE) without wheals is increasingly recognized as a clinical entity and a frequent cause of admission to the emergency room. The Hereditary Angioedema Working Group (HAWK) ...classification allowed the scientific community to go beyond the semantic confusion that dominated this topic for decades. This classification distinguishes hereditary and acquired forms of AE, either related or unrelated to C1 inhibitor deficiency. Recently, additional mechanisms have been involved in the AE pathogenesis, including the uncontrolled activation of factor XII, generation of vasoactive mediators that induce dysregulation of endothelial functions, and bidirectional interactions between mast cell-derived mediators and the plasma contact system. Thus, recurrent AE can be determined by multiple and concurrent mechanisms that may generate distinct clinical phenotypes of the disease. Frequency, severity, and the location of attacks are quite different from patient to patient and, even in the same patient, they may change throughout the course of life. The severity of the clinical phenotype strongly influences the burden of the disease and patients' quality of life. Despite major advances in our understanding of recurrent AE, many unsolved questions remain, leaving several unmet needs for patients and caregivers. This review is focused on a description of different AE phenotypes and the concurrent mechanisms leading to their pathogenesis. A better definition of cellular and molecular pathways responsible for the distinct AE phenotypes may help to improve diagnosis and may lead to a personalized approach to prophylaxis and treatment of the disease.
Introduction
The routine use of patient-reported outcomes (PROs) in clinical practice improves quality of care, it helps in reducing the access to emergency services and unscheduled visits, and it ...can improve cancer patients’ time survival. The Edmonton Symptom Assessment System (ESAS) is a PRO largely used in different care settings to monitor physical and psychological symptoms. Nonetheless, along with these symptoms, literature also highlighted the presence and effect of spiritual pain, financial distress, and social isolation on quality of care, treatment effectiveness, and survival.
Aim
The aims of the current study were (a) to complete the Italian version of the ESAS validation process by adding the missing symptom “insomnia” and (b) to develop and validate the ESAS–Total Care (ESAS-TC) that is intended to evaluate and screen not only physical and psychological symptoms but also spiritual pain, discomfort deriving from financial problems associated with illness, and suffering related to social isolation.
Methods
A sample of Italian native outpatients, who referred to the dedicated Supportive Care Unit of the Fondazione IRCCS, Istituto Nazionale deiTumori (INT), Milano, were asked to fill the ESAS-TC to assess item properties, factorial structure, internal consistency, test–retest reliability (patients were asked to retake the scale after 2–6 weeks), and external validity. Concerning the latter, other self-administered scales were employed to assess perceived stress (
Perceived Stress Scale
), unmet needs (using the
Need Evaluation Questionnaire
that describes informative, assistance/care, relational, needs for psycho-emotional support, material needs), and perceived social support (administering the
Multidimensional Scale of Perceived Social Support
that evaluates perceived support of family, friends, and significant others in the wider social field).
Results
The scales were administered to 243 patients with solid (90%) and hematologic (10%) cancers, mean age 62.6, female 76.5%. Analysis suggested that a single factor better represents the structure of the ESAS scales, their internal consistency and test–retest reliability were good, and evidence of construct and criterion validity were provided. Additionally, incremental validity of the ESAS-TC was proved showing that the added items offer a unique contribution in predicting the patient’s stress. Finally, known groups validity was confirmed testing the differences in the ESAS scores due to the Karnofsky Performance Status.
Conclusions
The current study allowed to complete the validation of the Italian version of the ESAS and to develop a psychometrically sound scale, the ESAS-Total Care, that potentially helps in moving cancer research toward personalized total cancer care.
Summary
Mast cells and basophils play a pathogenetic role in allergic, inflammatory, and autoimmune disorders. These cells have different development, anatomical location and life span but share many ...similarities in mechanisms of activation and type of mediators. Mediators secreted by mast cells and basophils correlate with clinical severity in asthma, chronic urticaria, anaphylaxis, and other diseases. Therefore, effective biomarkers to measure mast cell and basophil activation in vivo could potentially have high diagnostic and prognostic values. An ideal biomarker should be specific for mast cells or basophils, easily and reproducibly detectable in blood or biological fluids and should be metabolically stable. Markers of mast cell and basophil include molecules secreted by stimulated cells and surface molecules expressed upon activation. Some markers, such as histamine and lipid mediators are common to mast cells and basophils whereas others, such as tryptase and other proteases, are relatively specific for mast cells. The best surface markers of activation expressed on mast cells and basophils are CD63 and CD203. While these mediators and surface molecules have been associated to a variety of diseases, none of them fulfills requirements for an optimal biomarker and search for better indicators of mast cell/basophil activation in vivo is ongoing.
Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) ...and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network MASK) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
Summary
Background
Mobile technology may help to better understand the adherence to treatment. MASK‐rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient‐centred ICT system. A ...mobile phone app (the Allergy Diary) central to MASK is available in 22 countries.
Objectives
To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App.
Methods
An observational cross‐sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach.
Results
A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty‐six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non‐adherent to medications (MPR <70%). Of those, the largest group was non‐adherent to medications and the time interval was increased in 442 (36.68%) users.
Conclusion and clinical relevance
Adherence to treatment is low. The relative efficacy of continuous vs on‐demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication‐taking behaviour in a real‐world setting.
Background
In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is ...a need to support the transformation of the health care system into integrated care with organizational health literacy.
Main body
As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real‐life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self‐care through technology‐assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next‐generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real‐world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally‐enabled, integrated, person‐centred care.
Conclusion
In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
The erythrocyte sedimentation rate (ESR) in canine medicine has been replaced by the evaluation of a few sensitive markers of the acute-phase proteins. The aim of the study was to evaluate the ESR ...using a point-of-care (MINIPET, DIESSE Diagnostica Senese S.p.A.) device (ESR-MP) and to compare the results with the gold standard Westergren method (ESR-W) in dogs. One hundred and nineteen K3-EDTA blood samples for complete blood count were randomly selected and assayed for ESR. The reference interval (RI) was established using the percentile method. The coefficient of variation (CV) in intra-assay and interassay precision of ESR-MP was calculated. The analytical sensitivity (Se), specificity (Sp), positive predictive values (PPVs), and negative predictive values (NPVs) were calculated. Agreement between ESR-MP and ESR-W was assessed with Pearson correlation coefficient (r), Cohen concordance test (K), Passing-Bablok regression, and Bland–Altman plots. Ten canine samples (8.4%) were ruled out because of flag-error by the MINIPET instrument (4.2%) or because they showed the diphasic pattern in ESR-W (4.2%). The canine RI of ESR-MP was 0–10 mm/h. Precision was excellent in intra-assay (CV = 0.02) and interassay (CV = 0.32). The analytical characteristics of ESR-MP in nonanemic samples were as follows: Se = 0.82, Sp = 0.95, PPV = 0.82, and NPV = 0.95. The accuracy of ESR-MP was better than ESR-W in nonanemic samples (r = 0.87; K = 0.77) and lower in anemic subjects (Hct <37%) (r = 0.76; K = 0.69). The Passing-Bablok regression showed the presence of systematic error and the absence of proportional error only in nonanemic blood samples. The Bland–Altman plots gave negative average values due to the difference in RIs and an agreement in both ESRs. The ESR-MP results can be obtained with the same K3-EDTA tubes used for the blood count, in shortcut time, and at reduced costs using the MINIPET device. These investigations highlight that ESR-MP could be useful in canine clinical settings.
Canine immune-mediated hemolytic anemia (IMHA) is a life-threatening condition that is commonly associated with neutrophilia and monocytosis. Leukocyte ratios have been found to have prognostic value ...in humans and animals affected by a range of inflammatory, infectious, and neoplastic disorders. We hypothesized that in primary IMHA, neutrophil to lymphocyte (NLR), neutrophil to monocyte (NMR), band neutrophil to segmented neutrophil (BNR) and monocyte to lymphocyte (MLR) ratios would be higher in dogs that did not survive to discharge. Medical records of dogs diagnosed with IMHA at two veterinary teaching hospitals were retrospectively reviewed. Twenty-three of the 72 included dogs did not survive to discharge. NLR, NMR, BNR and MLR ratios were compared between dogs that survived to discharge and dogs that died or were euthanized. None of the ratios were significantly different between survivors and non-survivors (
P
= 0.14–0.99). Area under the Receiver Operating Characteristic (ROC) curve for prediction of non-survival ranged from 0.5 (95% confidence interval 0.38–0.62) for MLR to 0.61 (0.49–0.72) for NMR and was not significantly different from 0.5 for any ratio (
P
= 0.29–0.99). After exclusion of 31 dogs that received one or both immunosuppressive medications and blood transfusion before presentation, the area under the ROC curve for prediction of survival was significantly different from 0.5 for MLR (0.78,
P
= 0.01) and NMR (0.78,
P
= 0.0002). This study suggests that lower MLR and higher NMR may predict poorer prognosis in untreated dogs with IMHA.
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