Prediction of response to biological treatment with monoclonal antibodies in severe asthma

In recent years, major developments have occurred in severe asthma management. Different asthma phenotypes and subgroups have been identified and new treatment options have become available. A total of five monoclonal antibodies are currently approved in severe asthma treatment: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. These drugs have been shown to reduce exacerbations and to have an oral corticosteroid-sparing effect in many severe asthma patients. However, biological treatment is not successful in all patients and should be discontinued in non-responsive patients. Treating the right patient with the right biologic, and therefore biologic response prediction, has become a major point of interest in severe asthma management. A variety of response outcomes is utilized in the different clinical trials, as well as a huge range of potential predicting factors. Also, regarding the timing of the response evaluation, there are considerable differences between studies. This review summarizes the results from studies on predicting responses and responders to biological treatment in severe asthma, taking into account clinical, functional and inflammatory parameters assessed prior to the start of treatment as well as following a few months of therapy. In addition, future perspectives are discussed, highlighting the need for more research to improve patient identification and treatment responses in the field of biological treatment in severe asthma

Postoperative urinary retention:Risk factors, bladder filling rate and time to catheterization: an observational study as part of a randomized controlled trial

Background: Knowledge of risk factors for postoperative urinary retention may guide appropriate and timely urinary catheterization. We aimed to determine independent risk factors for postoperative urinary catheterization in general surgical patients. In addition, we calculated bladder filling rate and assessed the time to spontaneous voiding or catheterization. We used the patients previously determined individual maximum bladder capacity as threshold for urinary catheterization.Methods: Risk factors for urinary catheterization were prospectively determined in 936 general surgical patients. Patients were at least 18 years of age and operated under general or spinal anesthesia without the need for an indwelling urinary catheter. Patients measured their maximum bladder capacity preoperatively at home, by voiding in a calibrated bowl after a strong urge that could no longer be ignored. Postoperatively, bladder volumes were assessed hourly with ultrasound. When patients reached their maximum bladder capacity and were unable to void, they were catheterized by the nursing staff. Bladder filling rate and time to catheterization were determined.Results: Spinal anesthesia was the main independent modifiable risk factor for urinary catheterization (hyperbaric bupivacaine, relative risk 8.1, articaine RR 3.1). Unmodifiable risk factors were a maximum bladder capacity &lt;500 mL (RR 6.7), duration of surgery &gt;= 60 min (RR 5.5), first scanned bladder volume at the Post Anesthesia Care Unit &gt;= 250mL (RR 2.1), and age &gt;= 60 years (RR 2.0). Urine production varied from 100 to 200 mL/h. Catheterization or spontaneous voiding took place approximately 4 h postoperatively.Conclusion: Spinal anesthesia, longer surgery time, and older age are the main risk factors for urinary retention catheterization. Awareness of these risk factors, regularly bladder volume scanning (at least every 3 h) and using the individual maximum bladder capacity as volume threshold for urinary catheterization may avoid unnecessary urinary catheterization and will prevent bladder overdistention with the attendant risk of lower urinary tract injury.</p

Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 ± 16.7 years (mean ± SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications

The perceived waning of biologics in severe asthma

BACKGROUND: Biologics are highly effective in severe asthma and used at fixed dosing intervals. However, in clinical practice, dosing intervals are sometimes shortened if patients perceive a decreased biologic effect before the next administration. The occurrence and clinical relevance of this perceived waning of biological effect is unknown.OBJECTIVE: To explore (1) the frequency, severity and conditions, (2) associated symptoms and (3) relationship with clinical characteristics of the patient-perceived waning effect of biologics before the next administration.METHODS: Severe asthma patients receiving biological treatment ≥4 months were included. Based on 17 semi-structured patient interviews, we developed a questionnaire focusing on the waning effect of biologics before the next administration, which was distributed among 129 patients. Clinical characteristics, including asthma control (ACQ) and quality of life (AQLQ) scores, were collected from patient files.RESULTS: 65/101 patients who completed the questionnaire reported a waning of biological effect, graded as severe (median (IQR) 6.5 (5-7.5) on a 0-10 BORG-scale). Waning manifested in a broad spectrum of symptoms. Patients reporting waning had higher ACQ and lower AQLQ scores versus those without (p &lt; 0.05) and higher BORG-scores were associated with higher exacerbation rate (ρ = 0.309, p = 0.013). A third of all patients were in favor of extending or shortening their dosing interval.CONCLUSION: Two-thirds of severe asthma patients report waning of biologic effect at the end of the dosing interval, which is associated with poorer asthma control and quality of life. The diversity in observed waning of effect opens the way for research into more individualized dosing of biologics.</p