Impact of the Neck and/or Shoulder Pain on Self-reported Headache Treatment Responses - Results From a Pharmacy-Based Patient Survey.

Neck and/or shoulder pain (NSP) frequently occurs together with headache. Therefore, we explored how patients with and without concomitant NSP differ in their baseline characteristics and in perceived treatment responses to an analgesic. An anonymous survey was performed among 895 patients with headache (735 self-reported tension-type headache [TTH]) who used an analgesic fixed-dose combination containing 400 mg ibuprofen and 100 mg caffeine as a non-prescription treatment. NSP was abundant among patients in our survey (60%) and was associated with >1 additional day of headache per month. Patients with NSP reported predominantly sedentary work more frequently than those without (40 vs. 29%); they also reported physical tension/poor posture as a perceived trigger factor more frequently (70 vs. 16%). The reported pain reduction was comparable in those with and without concomitant NSP regardless of whether assessed as mean pain rating (from about 6 to 1.5 on a 10-point rating scale), patients experiencing a ≥50% in pain reduction (89.6 vs. 88.8%) or becoming pain-free within 2 h (57 vs. 64%). However, recurrence of pain and use of another dose within the same day were more frequent with than without NSP. We conclude that concomitant NSP is frequent in patients with headache but does not substantially alter responses to a non-prescription medication.

Correction to: Effect of Bacillus clausii Capsules in Reducing Adverse Effects Associated with Helicobacter pylori Eradication Therapy: A Randomized, Double-Blind, Controlled Trial.

In the original publication, the Second author name was incorrectly published as Marcos Perez III.

Effect of Bacillus clausii Capsules in Reducing Adverse Effects Associated with Helicobacter pylori Eradication Therapy: A Randomized, Double-Blind, Controlled Trial.

INTRODUCTION: Antibiotic treatment can alter the gut microbiome and cause short-term gastrointestinal adverse effects (AEs). This study assessed the efficacy of lyophilized capsules containing 2 × 109 spores of Bacillus clausii (Enterogermina®; Sanofi Synthelabo) in reducing AEs associated with Helicobacter pylori eradication therapy in Italy. METHODS: In this randomized, double-blind, single-center, phase IIIB study, 130 adult outpatients with H. pylori infection were assigned to receive one Enterogermina® capsule or placebo three times daily for 2 weeks (1:1). During week 1, all patients received clarithromycin 500 mg, amoxicillin 1 g, and rabeprazole 20 mg twice daily. The primary efficacy outcome was the presence of diarrhea in week 1. RESULTS: A total of 130 patients were randomized. The incidence of diarrhea in week 1 was 29% in the B. clausii group and 48% in the placebo group [relative risk (RR) 0.61; 95% confidence interval (CI) 0.39-0.97; p = 0.03]. The incidence of diarrhea remained lower with B. clausii than with placebo in week 2 (RR 0.38; 95% CI 0.14-1.02; p = 0.0422). In week 1, the number of days without diarrhea was significantly higher in the B. clausii group than in the placebo group (6.25 vs. 5.86; p = 0.0304). In both groups, the number of days without diarrhea increased significantly (p < 0.0001) from week 1 to week 2. A total of three AEs occurred in two patients in the placebo group, but none were serious. CONCLUSIONS: Compared with placebo, Enterogermina® reduced the incidence of, and the number of days with, diarrhea in patients receiving H. pylori eradication therapy. Enterogermina® was well tolerated.

Safety of ambroxol in the treatment of airway diseases in adult patients.

INTRODUCTION: Ambroxol is a widely used secretolytic and mucoactive over-the-counter agent primarily used to treat respiratory diseases associated with viscid mucus. Following post-marketing reports of hypersensitivity reactions and severe cutaneous adverse reactions (SCARs) possibly linked to ambroxol, the European Union's Pharmacovigilance Risk Assessment Committee (PRAC) initiated in April 2014 a review of the safety of ambroxol in all its registered indications, which was finalized in 2016. Areas covered: Here, we evaluate the clinical safety of ambroxol and provide an expert opinion on the benefit-risk balance of ambroxol in the treatment of adult patients with bronchopulmonary diseases. The evidence for this review is derived from clinical trials of ambroxol that were provided to the PRAC by the marketing authorization holders of ambroxol-containing medicines. Expert opinion: Clinical experience accumulated from randomized clinical trials and observational studies suggests that ambroxol is a safe and well-tolerated treatment of bronchopulmonary diseases, with a well-balanced and favorable benefit-risk profile. All reported adverse events were mild and self-limiting, and the risk of SCARs with ambroxol is low. Further investigations could address the safety and efficacy of ambroxol in pediatric lung diseases and in additional therapeutic indications, such as biofilm-dependent airway disease and lysosomal storage disorders.

Bacillus clausii for the Treatment of Acute Diarrhea in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Acute diarrhea is a burdensome disease with potentially harmful consequences, especially in childhood. Despite its large use in clinical practice, the efficacy of the probiotic Bacillus clausii in treating acute childhood diarrhea remains unclear. Our objective was to systematically review the efficacy of Bacillus clausii in the treatment of acute childhood diarrhea. The following electronic databases were systematically searched up to October 2017: MEDLINE (via PubMed/OVID), EMBASE (via OVID), Cochrane Central Database of Controlled Trials (via CENTRAL), Google Scholar, and ClinicalTrials.gov. Only randomized controlled trials were included. The overall effect for the meta-analysis was derived by using a random effects model. Six randomized controlled trials (1298 patients) met the eligibility criteria. Data arising from pooled analysis showed that Bacillus clausii significantly reduced the duration of diarrhea (mean difference = -9.12 h; 95% confidence interval [CI]: -16.49 to -1.75, p = 0.015), and the duration of hospitalization (mean difference = -0.85 days; 95% CI: -1.56 to -0.15, p = 0.017), compared with control. There was a trend of decreasing stool frequency after Bacillus clausii administration compared with the control group (mean difference = -0.19 diarrheal motions; 95% CI: -0.43 to -0.06, p = 0.14). Bacillus clausii may represent an effective therapeutic option in acute childhood diarrhea, with a good safety profile.

[More than expectorant: new scientific data on ambroxol in the context of the treatment of bronchopulmonary diseases]. / Mehr als ein Expektorans: neue wissenschaftliche Daten zu Ambroxol im Kontext der Behandlung bronchopulmonaler Erkrankungen.

BACKGROUND: Ambroxol has been established for decades in the treatment of acute and chronic respiratory diseases. In 2015, the European Medicines Agency reassessed the clinical benefit-risk ratio of the drug. OBJECTIVE: What new scientific data on ambroxol, which are relevant to the treatment of bronchopulmonary diseases, are available? METHOD: The review is based on a systematic literature research in medline with the search term "ambroxol" during the publication period 2006-2015. Non-relevant publications were excluded manually. RESULTS AND CONCLUSIONS: Ambroxol is still intensively researched. The traditional indication as an expectorant is confirmed. But there is also an ever better understanding of the various mechanisms of action as well as the ever more exact modeling of the structures under investigation. New fields of application are conceivable, e. g. in patients with severe pulmonary disease who undergo surgery or who are in intensive care, as an adjuvant in anti-infective therapies, especially in infections with biofilm-producing pathogens, or in rare diseases such as lysosomal storage diseases. However, final evidence of the clinical relevance in these fields of application is still missing.

Development of Covalent Ligand-Receptor Pairs to Study the Binding Properties of Nonpeptidic Neurotensin Receptor 1 Antagonists.

The neurotensin receptor NTS1 has been suggested to be of pharmaceutical relevance, as it was found to exert modulatory effects on dopaminergic signal transduction and to be involved in tumor progression. Rational drug design of NTS1 receptor ligands requires molecular insights into the binding behavior of a particular lead compound. Although crystal structures of NTS1 have revealed the molecular determinants of peptide-agonist interactions, the binding mode of small-molecule antagonists remains largely unknown. Employing a disulfide-based tethering approach, we developed covalently binding molecular probes. The ligands 1 and 2 are based on the pharmacophore of the nonpeptidic NTS1 antagonist SR142948A, allowing the formation of a disulfide bond to an engineered cysteine residue of NTS1. The position of the covalent bond between Cys127(2.65) and the ligand was used to predict the binding mode of the covalent antagonist 1 and its parent compound SR142948A by molecular dynamics simulations.

Development of a metabolically stable neurotensin receptor†2 (NTS2) ligand.

Subtype-selective neurotensin receptor 2 (NTS2) ligands can be used as molecular probes to investigate the physiological role of neurotensinergic systems and serve as lead compounds to initiate the development of drugs for the treatment of tonic pain. Starting from our recently described NTS2 ligand 1, structural variants of type 2 were synthesized to further improve binding affinity and selectivity to gain metabolic stability. The peptide-peptoid hybrid 2 b showed excellent NTS2 binding affinity (K(i) =2.8 nM) and 22 000-fold selectivity over NTS1, as well as metabolic stability over 32 h in a serum degradation assay. Employing a MAPK-driven luciferase reporter gene assay and an IP accumulation assay, the neurotensin mimetic 2 b displayed respective inhibitions of constitutive activity exceeding 4.3- and 3.9-fold that of the inverse agonist activity of the endogenous ligand neurotensin.

Radical arylation of tyrosine and its application in the synthesis of a highly selective neurotensin receptor 2 ligand.

A small library of Fmoc-protected 3-arylated tyrosines was created by radical arylation. The new building blocks were successfully applied in the synthesis of two novel neurotensin receptor ligands. Both isomers showed high affinity for the human NTS2 receptor with K(i) values in the nanomolar range. Interestingly, subtype selectivity strongly depends on the configuration of the peptide in position 11. Isomer (11R)-3 displayed an excellent preference for NTS2 compared to NTS1.

Discovery of highly potent and neurotensin receptor 2 selective neurotensin mimetics.

The neurotensin receptor subtype 2 (NTS2) is involved in the modulation of tonic pain sensitivity and psychiatric diseases and is, therefore, regarded as a highly attractive pharmacological target protein. Aiming to discover NTS2 selective ligands, we herein describe the identification of screening hits and the chemical synthesis of structural variants leading to the highly potent and NTS2 selective peptide-peptoid hybrids of type 3. The neurotensin mimetics 3a and 3e-g incorporating an N-(4-hydroxyphenethyl)glycine substructure exhibit single digit nanomolar affinity (K(i) = 4.3-8.8 nM) and 1900-12000 fold selectivity over the neurotensin receptor subtype 1 (NTS1). According to functional experiments, the test compounds 3a and 3e-g displayed an inhibition of constitutive mitogen-activated protein kinase (MAPK) activity exceeding 2.6-4.6 times the inverse agonist activity of the endogenous ligand neurotensin.