Immunogenic Yeast-Based Fermentation Product Reduces Allergic Rhinitis-Induced Nasal Congestion: A Randomized, Double-Blind, Placebo-Controlled Trial The article ‘‘Immunogenic Yeast-Based Fermentation Product Reduces Allergic Rhinitis-Induced Nasal Congestion: A Randomized, Double-Blind, Placebo-Controlled Trial’’, written by Mark A. Moyad, Larry E. Robinson, Julie M. Kittelsrud, Stuart G. Reeves, Susan E. Weaver, Aireen I. Guzman, Mark E. Bubak was originally published electronically on the publisher’s internet portal (currently Springer-Link) on 12 August, 2009.

Correction to: Liaoning Score for Prediction of Esophageal Varices in Cirrhotic Patients Who Had Never Undergone Endoscopy: A Multicenter Cross-Sectional Study in Liaoning Province, China Unfortunately, the fourteenth author’s name was incorrectly published in the Original Article. The correct author name is Cen Hong.

Letter: An Economic Evaluation of Iron Isomaltoside 1000 Versus Ferric Carboxymaltose in Patients with Inflammatory Bowel Disease and Iron Deficiency Anemia in Denmark

Factors Associated with Improvements in Patient-Reported Outcomes During Mirabegron or Antimuscarinic Treatment of Overactive Bladder Syndrome: A Registry Study (PERSPECTIVE) Abstract Introduction Patient-reported outcomes (PROs) provide valuable insights about the effectiveness of overactive bladder (OAB) treatments. The aim of PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder) was to provide real-world evidence from the USA and Canada on patient-perceived effectiveness and safety of mirabegron and antimuscarinics for treating OAB symptoms. Methods This prospective, non-interventional registry followed adult patients with OAB who were starting treatment with mirabegron or antimuscarinics. All treatment decisions were made at the discretion of the treating healthcare provider with no mandatory visits after enrollment. The primary objective was to identify factors associated with improved treatment effectiveness from a patient perspective mainly using the OAB Questionnaire Short-Form (OAB-q SF). The form was sent to patients via email link at baseline and months 1, 3, 6, and 12. Treatment-emergent adverse event (TEAE) data were collated from investigator reports. Results Overall, 1514 patients were included (female 73.5%, mean age 62.2 years). Mirabegron was initiated by 613 patients and antimuscarinics by 901 patients. A PRO response rate of approximately 60% was achieved (575 patients did not complete baseline PROs). Similar improvements in OAB-q SF symptom bother score and health-related quality of life (HRQoL) total score were observed for mirabegron and antimuscarinic initiators. Covariate-adjusted models demonstrated that worse baseline PRO score, Hispanic ethnicity, being treatment naïve, and use of complementary/supportive OAB therapies at baseline were significantly associated with greater improvements in both scores. The most frequent TEAEs were gastrointestinal disorders (dry mouth, constipation, and nausea) and nervous system disorders (headache, somnolence, and dizziness). Conclusion There are no differences between mirabegron and antimuscarinics in terms of patient-reported OAB symptom bother and HRQoL. Trial Registration ClinicalTrials.gov identifier, NCT02386072. Funding Astellas Pharma Global Development, Inc. Plain Language Summary Plain language summary available for this article.

Aspirin Versus Clopidogrel Monotherapy for the Treatment of Patients with Stable Coronary Artery Disease: A Systematic Review and Meta-Analysis Abstract Introduction Although aspirin (ASA) is the mainstay of treatment for the prevention of recurrent ischemic stroke, the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial showed ASA monotherapy to be inferior to clopidogrel in preventing recurrent adverse cardiovascular outcomes in patients with high cardiac risks. Here, we aimed to systematically compare ASA versus clopidogrel monotherapy for the treatment of patients with stable coronary artery disease (CAD). Methods Electronic databases were searched and studies were included if they compared ASA versus clopidogrel monotherapy for the treatment of patients with CAD and they reported adverse clinical outcomes. The latest version of RevMan software (version 5.3) was used as the statistical tool for the data analysis. Odds ratios (OR) and 95% confidence intervals (CI) were generated to interpret the data. Results A total number of 5497 patients (from years 2003 to 2011) were treated with ASA monotherapy, whereas 2544 patients were treated with clopidogrel monotherapy. Results of this analysis showed no significant difference in composite endpoints (cardiovascular death, myocardial infarction, and stroke) (OR 0.99, 95% CI 0.47–2.10; P = 0.98), all-cause mortality (OR 1.05, 95% CI 0.82–1.33; P = 0.71), cardiac death (OR 0.89, 95% CI 0.17–4.74; P = 0.89, myocardial infarction (OR 0.84, 95% CI 0.52–1.36; P = 0.48), stroke (OR 1.26, 95% CI 0.39–4.06; P = 0.70), and bleeding defined by the Bleeding Academic Research Consortium (BARC [grade 3 or above]) (OR 1.28, 95% CI 0.78–2.12; P = 0.33). Conclusion This analysis did not show any significant difference in all-cause mortality, cardiac death, myocardial infarction, stroke, and BARC grade 3 or above among CAD patients who were treated with either ASA or clopidogrel monotherapy. However, as a result of the limited data, this hypothesis should be confirmed in other major trials.

Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours Abstract Introduction A vast increase in knowledge of numerous aspects of malignant salivary gland tumours has emerged during the last decade and, for several reasons, this has not been the case in benign epithelial salivary gland tumours. We have performed a literature review to investigate whether an accurate histological diagnosis of the 11 different types of benign epithelial salivary gland tumours is correlated to any differences in their clinical behaviour. Methods A search was performed for histological classifications, recurrence rates and risks for malignant transformation, treatment modalities, and prognosis of these tumours. The search was performed primarily through PubMed, Google Scholar, and all versions of WHO classifications since 1972, as well as numerous textbooks on salivary gland tumours/head and neck/pathology/oncology. A large number of archival salivary tumours were also reviewed histologically. Results Pleomorphic adenomas carry a considerable risk (5–15%) for malignant transformation but, albeit to a much lesser degree, so do basal cell adenomas and Warthin tumours, while the other eight types virtually never develop into malignancy. Pleomorphic adenoma has a rather high risk for recurrence while recurrence occurs only occasionally in sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and the membranous type of basal cell adenoma. Papillomas, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (solid, trabecular and tubular subtypes) very rarely, if ever, recur. Conclusions A correct histopathological diagnosis of these tumours is necessary due to (1) preventing confusion with malignant salivary gland tumours; (2) only one (pleomorphic adenoma) has a considerable risk for malignant transformation, but all four histological types of basal cell adenoma can occasionally develop into malignancy, as does Warthin tumour; (3) sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and Warthin tumour only occasionally recur; while (4) intraductal and inverted papilloma, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (apart from the membranous type) virtually never recur. No biomarker was found to be relevant for predicting recurrence or potential malignant development. Guidelines for appropriate treatment strategies are given.

Treatment of Hypertensive and Hypercholesterolaemic Patients with the Triple Fixed Combination of Atorvastatin, Perindopril and Amlodipine: The Results of the CORAL Study Abstract Introduction Hypertension and hypercholesterolaemia are important contributors to the development and progression of atherosclerosis. The coexistence of these two conditions is rather common: hypercholesterolaemia is present in 40–60% of hypertensive patients. Remarkably, patient compliance with antihypertensive regimens is better than with statin therapy. Thus, the inclusion of statins and blood pressure-lowering agents into a fixed combination might even double the effectiveness of statin therapy, and thereby achieve significantly greater reduction of cardiovascular risk. The CORAL study was a 3-month, prospective, multicentre, observational, non-interventional survey, which evaluated the blood pressure- and lipid-lowering efficacy of the triple fixed combination of atorvastatin/perindopril/amlodipine, administered in various dose combinations. Methods The efficacy of the triple fixed combination was reflected by the changes of the blood pressure readings taken in the office and during 24-h blood pressure monitoring (3 months elapsed between visits 1 and 3). The laboratory parameters obtained during data acquisition were also recorded. Results After 3 months of therapy, mean office blood pressure decreased from 158.5 ± 16.7/91.7 ± 9.4 to 132.2 ± 8.3/80.1 ± 6.8 mmHg (p < 0.0001), whereas mean 24-h blood pressure decreased from 146.0 ± 14.5/82.5 ± 12.1 to 132.1 ± 13.2/75.6 ± 9.9 mmHg. With regard to metabolic parameters, the inclusion of pre-existing statin therapy in the fixed combination led to further, significant reduction of lipid parameters as follows: total cholesterol level from 6.18 ± 1.15 to 5.16 ± 0.88 mmol/L, LDL-cholesterol from 3.41 ± 1.01 to 2.80 ± 0.82 mmol/L and triglyceride level from 2.26 ± 1.17 to 1.82 ± 0.83 mmol/L (all p < 0.0001). Conclusion Treatment with the fixed triple combination of atorvastatin, perindopril and amlodipine might take us closer to the optimal therapy for hypertensive patients with hypercholesterolaemia. The expected improvement of patient adherence to treatment may result in an increase of the percentage patients who achieve both blood pressure control and the LDL-cholesterol targets recommended in guidelines. Moreover, this may translate into the further decline of the risk of prospective cardiovascular events. Funding Egis Pharmaceuticals.

Development of a Lyophilized Formulation of Pegaspargase and Comparability Versus Liquid Pegaspargase Abstract Introduction Pegaspargase, a pegylated asparaginase, is a core component in the treatment of acute lymphoblastic leukemia. Pegaspargase in liquid form has a limited shelf life of 8 months due to depegylation, leading to changes in purity and potency over time. Lyophilization is an approach that can improve the stability of biological drug conjugates. Methods Here we describe the development of a lyophilized formulation of pegaspargase and present results of a series of tests demonstrating that the lyophilized form has comparable physicochemical properties to the liquid form. Results Stability tests of critical quality attributes, including purity, potency, aggregates and total free polyethylene glycol, demonstrate that lyophilized pegaspargase remains stable for at least 3 years, with optimum stability achieved with storage under refrigerated conditions (2–8 °C). Conclusions Lyophilization improved the stability of pegaspargase without altering other physicochemical properties, permitting a prolonged shelf life of at least 2 years when stored at 2–8 °C. This may enable greater storage flexibility and allow for better management of pegaspargase. Funding Study Sponsor: Baxalta (now part of Takeda). Publication Sponsor: Servier Affaires Médicales.

Impact of Online Prescription Management Systems on Biologic Treatment Initiation Abstract Introduction Pharmaceutical firms have begun offering online prescription management systems to facilitate prescription processing. This study evaluated the impact of the HUMIRA Complete Pro (HCPro) online prescription management system on the rate of abandonment and the time to first fill for patients prescribed adalimumab (ADA). A retrospective cohort analysis of patients initiating ADA treatment with or without use of the HCPro online prescription processing system was used to evaluate the impact of HCPro on treatment initiation outcomes. Methods Patient-level data for patients with an ADA prescription processed through HCPro were mapped to Symphony Health claims for patients initiating ADA between January 2012 and January 2015. The sample included patients aged ≥ 18 years with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis who had data available 3 months before and after their first ADA claim (index date). Baseline characteristics, prescription abandonment rate, and time-to-first-prescription fill were compared between patients with a prescription processed through HCPro (HCPro cohort) and those without (non-HCPro cohort). The odds of abandonment were evaluated in the 3 months following the index date using a multivariate logistic regression model. Results The study included 24,767 patients (535 HCPro; 24,232 non-HCPro). HCPro patients had a greater frequency of initiation at a specialty pharmacy (66% vs. 56%; P < 0.001) and enrollment in AbbVie’s patient support program (71% vs. 51%; P < 0.001) as well as a lower copay for ADA ($206 vs. $265; P = 0.011). HCPro patients had a lower abandonment rate (6.4% vs. 13.9%; P < 0.001) and reduced days to prescription fill (7.0 vs. 14.4; P < 0.001). After controlling for baseline characteristics, abandonment odds were 43% lower for patients using HCPro (odds ratio = 0.57; P = 0.004). Conclusion Initiating ADA treatment with an online prescription management system (HCPro) significantly reduces the odds of abandonment and time to first prescription fill. Funding AbbVie Inc., Chicago, USA.

Inosine Pranobex: A Key Player in the Game Against a Wide Range of Viral Infections and Non-Infectious Diseases Abstract Inosine pranobex (IP), commonly known as inosine acedoben dimepranol, isoprinosine and methisoprinol, has been proven to positively impact the host’s immune system, by enhancing T-cell lymphocyte proliferation and activity of natural killer cells, increasing levels of pro-inflammatory cytokines, and thereby restoring deficient responses in immunosuppressed patients. At the same time, it has been shown that it can affect viral RNA levels and hence inhibit growth of several viruses. Due to its immunomodulatory and antiviral properties, and its safety profile, it has been widely used since 1971 against viral infections and diseases, among which subacute sclerosis panencephalitis, herpes simplex virus, human papilloma virus, human immunodeficiency virus, influenza and acute respiratory infections, cytomegalovirus and Epstein–Barr virus infections. Following an analysis of almost five decades of scientific literature since its original approval, we here summarize in vivo and in vitro studies manifesting the means in which IP impacts the host’s immune system. We also provide a synopsis of therapeutic trials in the majority of which IP was found to have a beneficial effect. Lastly, positive results from limited studies, suggesting the putative future use of IP in new therapeutic indications are briefly described. In order to support use of IP against viral infections apart from those already approved, and to establish its use in clinical practice, further well-designed and executed trials are warranted. Funding: Ewopharma International.