Background: Severe asthma is a major cause of morbidity. Some patients may benefit from biological therapies. Most evaluations of these treatments are derived from randomized controlled trials (RCTs), but few patients are eligible for these trials. Studies involving more diverse groups of participants exist, but there is a lack of precise pooled estimates.Objective: This systematic review aims to evaluate the real-world efficacy of recently and nearly licensed biological therapies for severe asthma to assess the generalizability of the RCT data.Methods: Clinical outcomes including exacerbation rate, oral corticosteroid usage, forced expiratory volume in 1 second (FEV 1 ) and fractional exhaled nitric oxide (FeNO) were examined. Studies were assessed for risk of bias using the Critical Appraisal Skills Programme checklist tool. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE).Results: A total of 21 studies examining biologicals in real-world settings were identified; they mostly focused on benralizumab and mepolizumab. The introduction of biologicals reduced the annualzsed exacerbation rate significantly by −3.79 (95% confidence interval [CI] −4.53, −3.04), −3.17 (95% CI −3.74, −2.59) and −6.72 (95% CI −8.47, −4.97) with benralizumab, mepolizumab and reslizumab, respectively. Likewise, improvements were observed in FEV 1 (0.17 L 95% CI 0.11, 0.24) and FeNO (−14.23 ppb 95% CI −19.71, −8.75) following the treatment with mepolizumab. After treatment with benralizumab, there was an increase in FEV 1 (0.21 L 95% CI 0.08, 0.34).
Conclusions:These data demonstrate that anti-IL5 biologicals may improve the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs. The data were mainly retrospective and unadjusted, so estimated effect sizes may not be reliable. More data are needed to acquire accurate effect estimates in different subpopulations of patients.
To our knowledge, this is the first report of two patients with documented IR with panitumumab being desensitized successfully with cetuximab. Though anecdotal reports suggest safety of panitumumab in patients following IR with cetuximab, panitumumab can also cause severe IR. Our experience suggests that in case of limited options, such patients can be successfully challenged with cetuximab in a hospital after appropriate desensitization and premedication. Further studies focusing on desensitization and identifying hypersensitivity profile of different anti-epidermal growth factor receptor antibodies are warranted.
Background. As the malignant potential of sessile serrated lesions/polyps (SSL/Ps) and traditional serrated adenomas (TSAs) has been clearly demonstrated, it is important that serrated polyps are identified and correctly classified histologically. Aim. Our aim was to characterize the clinicopathological features of a series of SSL/Ps & TSAs, to assess the accuracy of the pathological diagnosis, the incidence, and the rate of dysplasia in SSL/Ps & TSAs. Methods. We identified all colorectal serrated polyps between 01/01/2004 and 31/05/2016, by searching the laboratory information system for all cases assigned a “serrated adenoma” SNOMED code. All available and suitable slides were reviewed by one pathologist, who was blinded to the original diagnosis and the site of the polyp. Subsequently discordant cases, SSL/Ps with dysplasia, and all TSAs were reviewed by a second pathologist. Results. Over a 149-month period, 759 “serrated adenoma” polyps were identified, with 664 (from 523 patients) available for review. 41.1% were reviewed by both pathologists; 15.1% (100/664) were reclassified, with the majority being changed from SSL/P to hyperplastic polyp (HYP) (66/664; 9.9%). 80.3% of these HYPs were located in the left colon, and the majority exhibited prolapse effect. There were 520 SSL/Ps (92.2%) & 40 TSAs (7.1%). The majority of SSL/Ps were in the right colon (86.7%) and were small (64.5% <1 cm), while most TSAs were in the left colon (85.7%) and were large (73.1%≥1 cm). 6.7% of SSL/Ps exhibited dysplasia, the majority of which were large (66.7%≥1 cm). Following consensus review, 13/520 (2.5%) SSL/Ps were downgraded from SSL/P with dysplasia to SSL/P without dysplasia. Detection of SSL/Ps peaked in the most recent years reviewed (87.5% reported between 2013 and 2016, inclusive), coinciding with the introduction of “BowelScreen” (the Irish FIT-based colorectal cancer screening programme). Conclusions. Awareness of, and adherence to, diagnostic criteria is essential for accurate classification of colorectal polyps.
The primary aim was reduction in time between initial patient assessment and an appointment in the transient ischaemic attack (TIA) clinic. The secondary aim was to improve the quality of data recorded on the referral.
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