Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice

Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. Objective: In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy. Method: Ninety-three patients from four different centers in Turkey were included in the study. Conventional tests, including prick and intradermal skin tests, with commercial venom extracts and serum specific IgE (sIgE) levels for whole venoms were performed. An sIgE analysis for venom allergen components, including rApi m 1, rApi m 2, rApi m 10, rVes v 1, rVes v 5, were evaluated by immunoblotting. Results: In conventional test results, 17 of 35 patients with bee venom allergy were positive to honey bee venom, whereas 18 patients were positive to bee and wasp venoms. In 28 of 35 patients with bee venom allergy, the diagnosis was confirmed with CRD. CRD revealed a sensitivity of 80% in patients with bee venom allergy. According to conventional tests, 7 of 24 patients with vespid venom allergy demonstrated sensitivity only to Vespula species, whereas 17 patients revealed double positivity. The total diagnostic sensitivity of Ves v 1 and Ves v 5 was calculated as 87.5%. Ten of 23 patients with a history of hypersensitivity to both venoms showed double sensitivity with CRD; one patient had cross-reactivity, one patient was found to be sensitive only to bee venom, and, eight patients were sensitive only to Vespula species. Eleven patients had an uncertain history in terms of the culprit insect type and six of them had double sensitivity in CRD. Conclusion: CRD seemed to be more helpful in diagnosing vespid venom allergy than bee venom allergy. It can also discriminate clinically significant sensitizations from irrelevant ones.Research Fund of Istanbul University [TSA2017-26335]This work was supported by the Research Fund of Istanbul University (Project TSA2017-26335

Quality-of-life in insect venom allergy: validation of the Turkish version of the "Vespid Allergy Quality of Life Questionnaire" (VQLQ-T)

WOS: 000375708700019PubMed ID: 27247880Purpose: "Vespid Allergy Quality of Life Questionnaire (VQLQ)" has been used to assess psychological burden of disease. The aim of this study was to evaluate validity, reliability and responsiveness to interventions of the Turkish version. Methods: The Turkish language Questionnaire (VQLQ-T) was administered to 81 patients with bee allergy and 65 patients with vespid allergy from different groups to achieve cross-sectional validation. To establish longitudinal validity, the questionnaire was administered to 36 patients treated with venom immunotherapy. Results: The cross-sectional validation in patients with vespid venom allergy showed a correlation coefficient of 0.97 (Cronbach alpha). Spearman's correlation coefficient of the pretreatment VQLQ-T score with Expectation of Outcome (EoO) questionnaire score was 0.55 (p < 0.001). After treatment, correlation between VQLQ-T score and EoO score was 0.64 (p = 0.003) in these patients. The cross-sectional instrument validation for non-beekeepers with bee venom allergy yielded a correlation coefficient of 0.96 (Cronbach alpha). Spearman's correlation coefficient between pretreatment VQLQ-T score and EoO score was 0.47 (p < 0.001) and after treatment, correlation between VQLQ-T score and EoO score was 0.78 (p = 0.008) in these patients. These findings indicate cross-sectional validity of VQLQ-T. In the longitudinal validation, there was a positive correlation between EoO and VQLQ-T with a correlation coefficient of 0.562 (p < 0.001). While mean (+/- SD) VQLQ-T score was 5.27 (+/- 1.29) in pretreatment, it was 2.78 (+/- 1.01) after treatment (p < 0.001). The correlation between the mean change in VQLQ-T score and the mean change in EoO score was 0.42 (p = 0.011). Conclusions: The Turkish version of VQLQ-T enables measurement of Quality of Life (QoL) in patients with either vespid or bee venom allergy. Furthermore, responsiveness of this instrument demonstrates the questionnaire's ability to detect changes over time

Attitudes of adult asthma patients towards influenze vaccination

aydin, omur/0000-0002-3670-1728;WOS: 000395279400002PubMed: 28366139Introduction: It is known that viral infections trigger exacerbations in asthma patients. There are conflicting reports on whether influenza vaccine is preventive or not. In this study, we aimed to evaluate asthmatic patient's attitude towards influenza vaccine and to determine which factors affect this attitude. Materials and Methods: A questionnaire involving data about demographic information, co-morbidities, frequency of viral upper respiratory tract infections, subject's influenza vaccination status and attitude towards vaccination had been filled for our outpatient clinic asthma patients and also for healthy controls. Results were evaluated separately for the two groups and then compared to each other. Results: For the study; 108 asthma patients (91 female, 17 male) and 110 non-asthmatic controls (64 female, 46 male) were enrolled. In asthma group, vaccination rates were significantly higher in the previous year (40.7%) and nearly half of them stated that they do regularly have influenza shots every year. Contrast to this find; half of the patients in the control group stated that they do not need to vaccinate themselves and 26.2% said that they don't believe influenza vaccine has any preventive effect. Also in the asthma group, this ratio was similar to the control group (20.3%). In asthma group, 66.7% of the patients who had side effects at their previous shots did not want to vaccinate themselves this year (p= 0.02). More than a half of the patients (53.1%) whom did not have shots had an episode of viral upper respiratory tract infection this year and this rate was significantly lower in the vaccinated group (p= 0.00). This result highlights the preventive effect of vaccination. Conclusion: We found that asthma patients' knowledge on influenza infection and vaccine were insufficient and also their belief towards the preventive features of the vaccination was low. Informing and encouraging patients about preventive medicine through various activities and meetings would be crucial

The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice.

Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy

Omalizumab in the treatment of eosinophilic granulomatosis with polyangiitis (EGPA): single-center experience in 18 cases

Abstract Background Data are limited regarding the effectiveness of omalizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Our aim was to evaluate the clinical and functional effectiveness of omalizumab in patients with EGPA in long-term follow-up. Methods This study was a retrospective chart review of patients with EGPA who were treated with omalizumab injections between May 2012 and April 2018. Once treatment with omalizumab was started, data were collected at various time points: baseline, the 16th week, 1st year, and annually until the last evaluation. Results Eighteen patients (16F/2M) with a mean age of 48.61 ± 11.94 years were included. Data were available for all patients for the first year, 12 patients for the second year, 10 patients for the third  year, 8 patients for the fourth  year and 5 patients for the fifth year. All patients were on mean dosage of 15.77 ± 7.6 mg/day oral corticosteroid (OCS) as daily bases for mean 8.61 ± 4 years besides high-dose inhaler corticosteroid/long-acting beta agonist. Antineutrophil cytoplasmic antibodies (ANCA) were positive in 2  patients, and 8 patients were diagnosed as having vasculitis by skin biopsy, one patient had polyneuropathy, and one patient had cardiac involvement. By considering the individual responses of patients and the level of improvement at the last evalulation, 10 (55.6%) patients responded completely, 1 responded partially, and 7 (38.9%) had no improvement. Omalizumab worked as a steroid-sparing agent in all patients and the daily OCS dose was reduced with a mean dosage of 6.28 mg/day at the end of the first year. The mean OCS reduction time for the whole group was 4 months. A reduction in asthma exacerbations/hospitalizations, improvement in forced expiratory volume in 1 second, and no decrease in the eosinophil count during treatment with omalizumab were also observed. Conclusions Omalizumab improved asthma control in some patients with EGPA with uncontrolled asthma by reducing asthma exacerbations and oral steroid requirement. However, more data are needed before recommending widespread use of omalizumab in patients with EGPA

Therapy with omalizumab in patients with severe persistant allergic asthma: a real life data in Turkey

Omalizumab is a biologic agent, which has been shown to be effective in clinical trials in allergic, severe asthmatics. The aim of this study was to evaluate the clinical, functional effectiveness, and side effects of omalizumab in real-life conditions respectively. A total of 18 patients (female/male: 11/7) were included to the study. The mean +/- SD age, total IgE, disease duration were 41.8 +/- 11.2 years, 255.1 +/- 197.3 kU/L, 12.8 +/- 9.4 years, respectively. Eight patients had isolated mite, seven patiens had mite + other inhalant allergen, three patients had only other allergen sensitivity. Mean duration of omalizumab treatment (months +/- SD) was 15.1 +/- 8.6 (min-max 1-29) months. Omalizumab dose was 150 mg/month in five patients, 300 mg/month in five, 300 mg/15 days in three, 375 mg/15 days in four, 225 mg/15 days in one patient. Data at the date of last visit were compared with one year prior to omalizumab treatment. Mean systemic steroid dose reduced by 83% (14.7 +/- 14.6 vs. 3.2 +/- 8 mg), number of other asthma medications reduced by 28% (3.6 +/- 1.3 vs. 2.5 +/- 1.3) (p< 0.05). FEV1% values (53.5 +/- 21.2 vs. 64.5 +/- 23.5) did not significantly change. Mean numbers of exacerbations (20 +/- 57.6 vs. 0.4 +/- 0.7), emergency visits (16.5 +/- 46.1 vs. 0.4 +/- 1.2), hospitalizations (2.1 +/- 2.6 vs. 0.1 +/- 0.3) decreased by 93%, 95%, 86%, respectively (p< 0.05). ACT scores increased by 94% (10.4 +/- 3.4 vs. 20.4 +/- 5.7) (p< 0.05). Fifteen patients (88%) were stated as responsive to treatment with omalizumab. Eleven patients (64.8%) stated that their expectations are met, three patients (17.6%) stated that their expectations are close to being met, three patients (17.6%) stated that their expectations are not met. A local side effect was seen in one patient. In conclusion, our data has shown that omalizumab is effective, and safe in severe allergic asthmatics under real-life conditions

Churg-Strauss syndrome: a new endotype of severe asthma? Results of 14 Turkish patients

IntroductionChurg-Strauss syndrome (CSS) is a rare multisystem vasculitis. Considering the variation of autoimmune diseases in different races, it is of interest to determine whether any outstanding features exist for Turkish patients with CSS

Erratum to: Allergen immunotherapy for insect venom allergy: protocol for a systematic review (vol 6, 6, 2016)

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy.METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised.DISCUSSION: The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT