Label-free quantitative proteomic profiling reveals differential plasma protein expression in patients with obesity after treatment with liraglutide

Introduction: Treatment and management of obesity is clinically challenging. The inclusion of GLP-1 receptor agonists (GLP1RA) in the medical management of obesity has proven to be efficacious. However, mechanisms underlying the molecular changes arising from GLP1RA treatment in patients with obesity remain to be elucidated. Methods: A single-center, prospective study was undertaken to evaluate the changes in the plasma proteins after liraglutide 3 mg therapy in twenty patients (M/F: 7/13) with obesity (mean BMI 40.65 ± 3.7 kg/m2). Anthropometric and laboratory parameters were measured, and blood samples were collected at two time points: baseline, before initiating treatment (pretreatment group, PT), and after three months of receiving the full dose liraglutide 3 mg (posttreatment group, PoT). An untargeted label-free LC MSMS mass spectrometric approach combined with bioinformatics and network pathway analysis was used to determine changes in the proteomic profiles. Results: The mean age of the study participants was 36.0 ± 11.1 years. A statistically significant change was observed in weight, BMI and HbA1c levels between the PT and PoT groups (paired t-test, P < 0.001). A significant dysregulation was noted in the abundances of 151 proteins (31 up and 120 downregulated) between the two groups. The potential biomarkers were evaluated using receiver operating characteristic (ROC) curves. The top ten proteins (area under the curve (AUC) of 0.999 (95% CI)) were identified as potential biomarkers between PT and PoT groups and included Cystatin-B, major vault protein, and plastin-3, which were upregulated, whereas multimerin-2, large ribosomal P2, and proline–rich acidic protein 1 were downregulated in the PoT group compared with the PT group. The top network pathway identified using ingenuity pathway analysis (IPA), centered around dysregulation of MAPK, AKT, and PKc signaling pathways and related to cell-to-cell signaling and interaction, cellular assembly and organization, cellular compromise and a score of 46 with 25 focus proteins. Discussion: Through label-free quantitative proteomic analysis, our study revealed significant dysregulation of plasma proteins after liraglutide 3 mg treatment in patients with obesity. The alterations in the proteomic profile between the PT and PoT groups demonstrated a decrease in levels of proteins involved in inflammation and oxidative stress pathways. On the other hand proteins involved in the glycolytic and lipolytic metabolic pathways as well as those participating in cytoskeletal and endothelial reorganization were observed to be increased. Understanding actions of liraglutide at a molecular and proteomic levels provides a holistic look into how liraglutide impacts metabolism, induces weight loss and improves overall metabolic health

Metabolomic Effects of Liraglutide Therapy on the Plasma Metabolomic Profile of Patients with Obesity

Background: Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP1RA), is a well-established anti-diabetic drug, has also been approved for the treatment of obesity at a dose of 3 mg. There are a limited number of studies in the literature that have looked at changes in metabolite levels before and after liraglutide treatment in patients with obesity. To this end, in the present study we aimed to explore the changes in the plasma metabolomic profile, using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in patients with obesity. Methods: A single-center prospective study was undertaken to evaluate the effectiveness of 3 mg liraglutide therapy in twenty-three patients (M/F: 8/15) with obesity, mean BMI 40.81 ± 5.04 kg/m2, and mean age of 36 ± 10.9 years, in two groups: at baseline (pre-treatment) and after 12 weeks of treatment (post-treatment). An untargeted metabolomic profiling was conducted in plasma from the pre-treatment and post-treatment groups using LC-HRMS, along with bioinformatics analysis using ingenuity pathway analysis (IPA). Results: The metabolomics analysis revealed a significant (FDR p-value ≤ 0.05, FC 1.5) dysregulation of 161 endogenous metabolites (97 upregulated and 64 downregulated) with distinct separation between the two groups. Among the significantly dysregulated metabolites, the majority of them were identified as belonging to the class of oxidized lipids (oxylipins) that includes arachidonic acid and its derivatives, phosphorglycerophosphates, N-acylated amino acids, steroid hormones, and bile acids. The biomarker analysis conducted using MetaboAnalyst showed PGP (a21:0/PG/F1alpha), an oxidized lipid, as the first metabolite among the list of the top 15 biomarkers, followed by cysteine and estrone. The IPA analysis showed that the dysregulated metabolites impacted the pathway related to cell signaling, free radical scavenging, and molecular transport, and were focused around the dysregulation of NF-κB, ERK, MAPK, PKc, VEGF, insulin, and pro-inflammatory cytokine signaling pathways. Conclusions: The findings suggest that liraglutide treatment reduces inflammation and modulates lipid metabolism and oxidative stress. Our study contributes to a better understanding of the drug’s multifaceted impact on overall metabolism in patients with obesity

'Real-life' effectiveness studies of omalizumab in adult patients with severe allergic asthma : Systematic review

We reviewed 24 ‘real-life’ effectiveness studies of omalizumab in the treatment of severe allergic asthma that included 4117 unique patients from 32 countries with significant heterogeneity in patients, clinicians and settings. The evidence underscores the short- and long-term benefit of anti-IgE therapy in terms of the following: improving lung function; achieving asthma control and reducing symptomatology, severe exacerbations and associated work/school days lost; reducing healthcare resource utilizations, in particular hospitalizations, hospital lengths of stay and accident specialist or emergency department visits; reducing or discontinuing other asthma medications; and improving quality of life – thus confirming, complementing and extending evidence from randomized trials. Thus, omalizumab therapy is associated with signal improvements across the full objective and subjective burden of illness chain of severe allergic asthma. Benefits of omalizumab may extend up to 2–4 years, and the majority of omalizumab-treated patients may benefit for many years. Omalizumab has positive short- and long-term safety profiles similar to what is known from randomized clinical trials. Initiated patients should be monitored for treatment response at 16 weeks. Those showing positive response at that time are highly likely to show sustained treatment response and benefit in terms of clinical, quality of life and health resource utilization outcomes

“Real-life” effectiveness studies of omalizumab in adult patients with severe allergic asthma : Meta-analysis

Background After the approval of omalizumab for severe allergic asthma, a total of 25 studies have evaluated the effectiveness of omalizumab under “real-life” conditions of heterogeneity in patients, clinicians, sites, and treatment patterns. Objective We conducted a meta-analysis to evaluate the effectiveness of omalizumab focusing on treatment response, lung function, quality of life, symptom control, corticosteroid use, and exacerbations and hospitalizations at 4-6, 12, and 24 months. Methods We searched PubMed and Embase for real-life studies on omalizumab in severe asthma published up to 2015. Three effect size types were extracted: single-point proportions; mean ± SD of change relative to baseline as raw numbers and standardized as Cohen's d; and changes in proportions of patients as relative risk. Random-effects meta-analyses were performed to account for within- and between-study heterogeneity. Studies were weighted by the DerSimonian and Laird method. Results Per data available at the 3 time points, omalizumab therapy was consistently associated with large proportions of patients classified as “good” to “excellent” treatment responders (Global Evaluation of Treatment Effectiveness scale); improvements in forced expiratory volume in 1 second, quality of life (Asthma-related Quality-of-Life Questionnaire scale), and asthma symptom control (Asthma Control Test scale); reductions in oral and inhaled corticosteroid (ICS) use; and reductions in exacerbations and hospitalizations. Conclusions This meta-analysis of noncontrolled studies documents the real-life pharmacotherapeutic effectiveness of omalizumab, as add-on treatment to ICS ± long-acting β2-agonists agents, in improving outcomes in patients with severe allergic asthma under conditions of heterogeneity in patients, clinicians, sites, and treatment patterns. The results mirror, complement, and extend the efficacy data from randomized controlled trials

Attitude and knowledge of Saudi community pharmacists towards use of proton pump inhibitors

Introduction: Proton pump inhibitors (PPIs) effectively suppress acid secretion and play an important role in peptic ulcer disease and gastroesophageal reflux disease. There is a real concern about the overutilization of PPIs, which will lead to significant high cost and undesirable outcomes. Despite that most of PPIs are classified as prescribed medications, yet most of their users take them without prescription in Saudi Arabia. Therefore, it was important to understand community pharmacists practice in dealing with PPIs and to evaluate their despising pattern of these medications. Method: A cross-sectional survey-based study that was carried out between September and December 2017. The survey intended to evaluate the knowledge and attitude of CPs towards use of proton pump inhibitors and was built as an online survey. Results: The results of this study showed that almost all CPs prescribe anti-ulcer drugs for their patients. Most of the participants (68.4%) have prescribed PPI for acute gastritis (68.4%), prophylaxis for stress ulcers (17.7%) and stress ulcer (11.1%). 54.9 percent of the participants recommend using acid suppression drugs for 1 to 2 weeks when they prescribe them to their patients. Thirty-two percent of the respondents had reported adverse events with PPIs. The study showed a significant association between length of work experience in community pharmacy and reporting adverse events. Conclusion: Community pharmacists in Saudi Arabia usually recommend and prescribe PPIs to their patients. Most of them have some knowledge on PPIs indications and side effects. Managing OTC PPI use in the community pharmacy setting is necessary to promote both patient and medication safety. Keywords: PPIs, Community pharmacy, Perception, Attitud

‘Real-world’ effectiveness of omalizumab in adults with severe allergic asthma : A meta-analysis

Background: Severe asthma affects 5–10% of the 350 million people with asthma worldwide. Findings from the authors’ previous meta-analysis supported omalizumab use as an adjuvant treatment for severe allergic asthma. The publication of fourteen new articles necessitates an update of the meta-analysis. Objective: To evaluate the ‘real-world’ effectiveness of omalizumab in the treatment of acute allergic asthma in adults by calculating pooled effects estimates from data in published articles. Methods: Articles on omalizumab effectiveness in ‘real-world’ settings were identified. Effect sizes, including point estimates of the proportion of patients who met a given criteria, mean improvements relative to baseline, and change in the proportion of patients requiring oral corticosteroids compared to baseline were extracted. Meta-analysis of proportions was conducted to pool effect sizes based on proportions. Standardized mean differences (Hedges’ g) were calculated from means and standard deviations. Relative risk was calculated from changes in proportions. Variability within and between studies was evaluated. Results: Omalizumab increases the percentage of individuals rated ‘good’ or ‘excellent’ on the Global Evaluation of Treatment Effectiveness Scale. Omalizumab also improves respiratory function, quality-of-life, and asthma control while reducing medication usage, exacerbations, hospitalizations, and adverse events. Conclusion: ‘Real-world’ evidence continues to support the use of omalizumab as adjuvant treatment for severe allergic asthma

Short- and long-term real-world effectiveness of omalizumab in severe allergic asthma : Systematic review of 42 studies published 2008-2018

Introduction: Omalizumab is a recombinant monoclonal anti-IgE antibody approved in the US as add-on treatment in moderate-to-severe allergic asthma (in severe allergic asthma [SAA] in Europe). A 2016 review of 24 real-world effectiveness studies in SAA published between 2008–2015 concluded that omalizumab was associated with significant improvements in objective and subjective outcomes with benefits extending beyond 2 years. Several new real-world studies have been published since, bringing the total to 42 studies. Areas covered: This systematic review of 42 studies published since 2008 updates and extends the 2016 review on the real-word evidence on omalizumab in SAA. It offers greater granularity as to time windows within which outcomes are reported and includes studies extending well beyond 4 years post omalizumab initiation. Expert commentary: This review firmly establishes the short-term effectiveness of omalizumab in adolescent and adult patients with SAA at 1 year, and provides strong evidence of long-term effectiveness up to 4 years and emergent evidence of effectiveness beyond 4 years. In the aggregate, these 42 studies underscore the long-term effectiveness of omalizumab in terms of: reducing exacerbations and symptoms, achieving asthma control, improving lung function, enhancing quality of life, decreasing emergency department visits and hospitalizations, and promoting concomitant medication-sparing

Predictability of the Implant Procedure on the Edentulous Ridge

Background: Since the development of the cone-beam computed tomography (CBCT) has been utilized in dentistry. It has almost become the gold standard to plan the dental implant before the surgery. The image of the CBCT can help the surgeon to evaluate the anatomy carefully before the procedure to be more prepared. Despite the value of the radiology evaluation, the implant procedures may require more consideration rather than evaluating the anatomical factors. The purpose of this study is to evaluate the predictability of using the cone beam computed tomography (CBCT) alone to plan for implant placement. Method: CBCT images were analyzed by a periodontist, measuring the ridge heights and widths of 12 selected teeth in the maxillary and mandibular arches for 91 patients planning for the implant-supported overdenture. Selected sites were investigated if the implants could be placed with or without additional augmentation procedures by reviewing the CBCT. The patient’s dental records were reviewed and compared with the planned procedure to investigate the predictability. Result: A total of 47 patients out of the 91 had completed the implant placement on the edentulous ridge, contributing to a total of 57 upper or lower teeth implants. Based on the mixed-effects logistic regression model results, we observe that the probabilities of having the planned treatments as the digital planning are only 0.38 and 0.57, respectively, for the cases suggested with/without additional augmentation. Both predictabilities are low, implying the CBCT planning for implant placement on the edentulous ridge is not a good index. It is insufficient to predict the surgical procedures as a solo method. Conclusion: According to our findings, it was shown that digital planning alone is insufficient to serve as an individual tool to predict implant placement. Further information is required to be considered for implant placement on the edentulous ridg