Historical cohort study examining comparative effectiveness of albuterol inhalers with and without integrated dose counter for patients with asthma or chronic obstructive pulmonary disease

This study was supported financially by an unrestricted grant from Teva Pharmaceuticals, Frazer, PA, USA. The authors thank Jenny Fanstone of Fanstone Medical Communications Ltd., UK, and Elizabeth V Hillyer for medical writing support, funded by Research in Real-Life. We acknowledge with gratitude Dr Ruchir Parikh for his review of and contributions to the manuscript.Peer reviewedPublisher PD

Changes in initial COPD treatment choice over time and factors influencing prescribing decisions in UK primary care : a real-world study

Acknowledgements Samantha Holmes (CircleScience, an Ashfield Company, part of UDG Healthcare plc) and Paul Hutchin (contracted to CircleScience, an Ashfield Company, part of UDG Healthcare plc) provided medical writing assistance. Funding The study was funded by Novartis Pharma AG (Basel, Switzerland).Peer reviewedPublisher PD

Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice

Purpose: Acute, severe asthma exacerbations can be difficult to predict and thus prevent. Patients who have frequent exacerbations are of particular concern. Practical exacerbation predictors are needed for these patients in the primary-care setting.Patients and methods: Medical records of 130,547 asthma patients aged 12–80 years from the UK Optimum Patient Care Research Database and Clinical Practice Research Datalink, 1990–2013, were examined for 1 year before (baseline) and 1 year after (outcome) their most recent blood eosinophil count. Baseline variables predictive (P<0.05) of exacerbation in the outcome year were compared between patients who had two or more exacerbations and those who had no exacerbation or only one exacerbation, using uni- and multivariable logistic regression models. Exacerbation was defined as asthma-related hospital attendance/admission (emergency or inpatient) or acute oral corticosteroid (OCS) course.Results: Blood eosinophil count >400/µL (versus ?400/µL) increased the likelihood of two or more exacerbations >1.4-fold (odds ratio [OR]: 1.48 (95% confidence interval [CI]: 1.39, 1.58); P<0.001). Variables that significantly increased the odds by up to 1.4-fold included increasing age (per year), female gender (versus male), being overweight or obese (versus normal body mass index), being a smoker (versus nonsmoker), having anxiety/depression, diabetes, eczema, gastroesophageal reflux disease, or rhinitis, and prescription for acetaminophen or nonsteroidal anti-inflammatory drugs. Compared with treatment at British Thoracic Society step 2 (daily controller ± reliever), treatment at step 0 (none) or 1 (as-needed reliever) increased the odds by 1.2- and 1.6-fold, respectively, and treatment at step 3, 4, or 5 increased the odds by 1.3-, 1.9-, or 3.1-fold, respectively (all P<0.05). Acute OCS use was the single best predictor of two or more exacerbations. Even one course increased the odds by more than threefold (OR: 3.75 [95% CI: 3.50, 4.01]; P<0.001), and three or more courses increased the odds by >25-fold (OR: 25.7 [95% CI: 23.9, 27.6]; P<0.001).Conclusion: Blood eosinophil count and several other variables routinely available in patient records may be used to predict frequent asthma exacerbations

Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety

Teduglutide is a glucagon-like peptide-2 (GLP-2) analog employed in patients with short bowel syndrome (SBS) to reduce the need of parenteral nutrition in these patients, by virtue of its effects on enteric function. The experimental studies reported that the stimulating action of GLP-2 on epithelial turnover implies the potential development of dysplastic and neoplastic lesion. However, the clinical trials could not detect preneoplastic lesions on histologic material, and in a recent pilot study the occurrence of polyps was similar before and after treatment and included only low-grade dysplastic lesions. Another clue in GLP-2 function in stimulating mucosal restore is its enhancement through cooperation with epidermal growth factor (EGF). In this study, we analyzed gastroscopy and colonoscopy samplings from a child successfully weaned off parenteral nutrition with teduglutide. Villous and crypt structure was regular both in duodenal and in colonic samplings; in properly oriented villi, villus/crypt ratio was regular. The absorptive epithelium demonstrated a regular morphology. No atypia was detected in enterocytes, along epithelial structures. At the ultrastructural analysis, only a few enterocytes with vacuolized cytoplasm were observed. An S-phase marker Ki67 stained nuclei in the transitional amplifying zone, while nuclei stained by the cell cycle regulatory proteins p21 and p27 were placed in the differentiated epithelium of the duodenal villi and colonic crypts, as in the control cases. The counts of enterocytes immunostained with the same antisera, evaluated with image analysis software, were in the range of control cases. The ratio of the number of epidermal growth factor receptor (EGFR) signals/the number of centromere probe of chromosome 7 (CEP7) signals was less than 2. The findings available from this single patient are consistent with good preservation of functional capability of intestinal epithelium after treatment with GLP-2, given the histologic and ultrastructural features of enterocytes. In addition, the findings from cell cycle regulatory proteins immunolocalization and quantitative analysis show that cell renewal machinery in our case is comparable to control cases. The gene of the receptor EGFR is regularly expressed in enteric epithelium of our case. Morphologic and functional data from our patient improve evidence in favor of the safety of GLP-2 employ in SBS

Erratum : Changes in initial COPD treatment choice over time and factors influencing prescribing decisions in UK primary care: a real-world study

Peer reviewedPublisher PD

Alternative approaches for probabilistic precipitation forecasting

Bayesian Model Averaging (BMA) and Bayesian Hierarchical Model (BHM) are statistical postprocessing techniques for calibrating precipitation forecast ensembles. BMA is a mixture model of predictive densities, while BHM is a fully Bayesian alternative to BMA. Both techniques are applied on a case-study. BMA is applied to quantitative Precipitation, yielding a better calibration than the ensemble in homogeneous areas. For qualitative precipitation, both BMA and BHM forecasts are more calibrated than the ensemble. However, BHM yields a worse performance due to the “shrinkage” effect, that lets the forecasts vary across a small range of values

Non-Invasive Diagnosis of Pediatric Intestinal Graft-Versus-Host Disease: A Case Series

Intestinal graft-versus-host disease (I-GvHD) represents a life-threatening complication in allogeneic stem cell transplantation (SCT). Unfortunately, non-invasive validated diagnostic tools to diagnose I-GvHD, evaluate treatment response, and guide the duration of immunosuppression are still lacking. We employed standard ultrasound and power Doppler to diagnose and follow up on pediatric intestinal GvHD. We herein report on three patients, prospectively evaluated among 24 pediatric patients referred to our center for allogeneic SCT. These three patients presented abdominal pain and diarrhea within the first 200 days after transplantation. In the reported cases, we performed small- and large-intestine ultrasound (US) at clinical onset of lower-intestinal symptoms and, when intestinal GvHD was confirmed, at GvHD flares, if any, and at follow-up. US constantly (3/3 patients) revealed increased bowel wall thickening (BWT) with different bowel segments’ involvement from patient to patient. Further, a moderate or strong increased Doppler signaling was seen in 2 out of 3 patients, according to clinical GVHD staging (e.g., the more the increase, the more the staging). Standard sonography corroborated GvHD diagnosis in all patients considered and was able to detect GvHD progression or complete normalization of findings, thus simplifying ensuing clinical decisions. Our report highlights the need to design clinical trials for the validation of non-invasive radiologic tools for diagnosis and follow-up of GvHD, especially in pediatric patients