Biologic drugs in adult onset Still’s disease: a systematic review and meta-analysis of observational studies

<p><b>Background</b>: Biological drugs, mainly interleukin (IL)-1 and IL-6 antagonists, but also tumor necrosis factor (TNF) inhibitors, have been used in the treatment of adult onset Still’s disease patients (AOSD).</p> <p><b>Methods</b>: We summarised the available evidence for the effectiveness of biologic drugs in AOSD. A systematic review of the literature was performed in order to identify all the available data concerning the effectiveness of biologic drugs in AOSD. The proportion of patients achieving complete remission or any clinical response was calculated. The meta-analysis was thus performed using a random-effects model accounting for the expected high level of heterogeneity.</p> <p><b>Results</b>: Nineteen observational published studies were included in the meta-analysis. The pooled analysis under a random-effects model showed an overall rate of clinical response of 0.85 (95% CI: 0.77–0.91, p < 0.0001) and an overall rate of complete remission of 0.66 (95% CI: 0.54–0.77, p = 0.01). The heterogeneity across studies was high (Q = 59.82 with df = 19.0, p < 0.0001, I² = 68.23%).</p> <p><b>Conclusions</b>: Our meta-analysis suggests that AOSD patients may experience a clinical response and/or a complete remission when treated with biologic drugs. Specifically designed and powered studies are needed to fully investigate the role of such medications in the management of AOSD patients.</p

Receiver operator characteristic (ROC) curve of mean value DAS28(ESR) in predicting the development of type 2 diabetes (T2D).

<p>Receiver operator characteristic (ROC) curve of mean value DAS28(ESR) in predicting the development of type 2 diabetes (T2D).</p

Study design.

<p>* In the pre-recruitment screening phase, patients were excluded if presented: 1) past diagnosis of T2D previously performed by a physician <i>or</i> 2) current or past treatment with antidiabetic medications (including oral antidiabetic drugs and insulin); 3) fasting plasma glucose (FPG) ≥ 126 mg/dL in at least two separate occasions. ** In the recruitment screening phase patients were excluded if fasting plasma glucose (FPG) ≥ 126 mg/dL.</p

Logistic regression analysis for prediction of new-onset impaired fasting glucose.

<p>Logistic regression analysis for prediction of new-onset impaired fasting glucose.</p

Logistic regression analysis for prediction of new-onset type 2 diabetes.

<p>Logistic regression analysis for prediction of new-onset type 2 diabetes.</p

Demographic and clinical characteristics of the study cohort.

<p>Demographic and clinical characteristics of the study cohort.</p

Receiver operator characteristic (ROC) curve of mean value DAS28(ESR) in predicting the development of type 2 diabetes (T2D).

<p>Receiver operator characteristic (ROC) curve of mean value DAS28(ESR) in predicting the development of type 2 diabetes (T2D).</p

Monitoring safety and use of old and new treatment options for type 2 diabetic patients: a two-year (2013–2016) analysis

<p><b>Objective</b>: To compare patients’ and physicians’ perceptions regarding effectiveness and tolerability of non-insulin hypoglycemic drugs in a cohort of type 2 diabetic patients; to verify whether a possible tridimensional link between effectiveness, tolerability, and adherence affects long-term therapeutic outcomes.</p> <p><b>Methods</b>: A two-year observational study was performed in 1389 Type 2 diabetic patients by involving general practitioner clinics and Diabetes Centers. A decimal scale and the Morisky questionnaire were used, respectively, to assess effectiveness and tolerability perceptions, and medication adherence.</p> <p><b>Results</b>: Physicians perceived therapy as more efficacious compared to their patients: perceived effectiveness was steady for physicians during the study whereas patients’ perception not significantly decreased (mean score from >8 to 7.84 ± 1.69). Physicians assigned higher tolerability scores compared to patients but only at the beginning of the study; interestingly, physicians’ tolerability perception was poorer than patients’ perception at last follow-up (mean score = 7.57 ± 1.40 vs. 7.88 ± 1.84). Favorable (score >7) patients’ perceptions about treatment effectiveness and tolerability were associated with higher adherence. Patients showed medium adherence across the study.</p> <p><b>Conclusions</b>: A mutual relationship between clinical effectiveness, adverse drug reactions, and adherence has been established, significantly impacting the clinical management of diabetic patients. A careful monitoring of this link by clinicians appears therefore necessary.</p

Synthesis and Biological Characterization of 3‑Substituted 1<i>H</i>‑Indoles as Ligands of GluN2B-Containing <i>N</i>‑Methyl‑d‑aspartate Receptors. Part 2

In the course of the identification of new indole derivatives targeting GluN2B-subunit-containing <i>N</i>-methyl-d-aspartate (NMDA) receptor, the (<i>N</i>-1<i>H</i>-indol-6-methanesulfonamide-3-yl)-2-(4-benzylpiperidin-1-yl)­ethanone (<b>10b</b>) was identified as a potent ligand for this NMDA receptor subunit. It displays very high binding affinity (IC₅₀ of 8.9 nmol) for displacement of [³H]­ifenprodil, thus showing improved potency with respect to the previously reported analogues as confirmed by functional assay. This finding was consistent with the docking pose of compound <b>10b</b> within the binding pocket localized in the GluN1-GluN2B subunit interface of NMDA receptor tetraheteromeric complex

Adverse drug reactions reporting in Calabria (Southern Italy) in the four-year period 2011-2014: impact of a regional pharmacovigilance project in light of the new European Legislation

<p><b>Background</b>: The number of suspected adverse drug reactions (ADRs) yearly submitted to the Italian Network of Pharmacovigilance (RNF) has progressively increased after the new European Pharmacovigilance legislation (July 2012). These results have mostly reflected the agreements between Italian Medicines Agency (AIFA) and Italian Regions, enabling the implementation of active pharmacovigilance projects. A project was funded by the AIFA in Calabria region (Southern Italy) in 2010 to increase ADRs reporting and promote a safer medicines’ use. Based on this background, we investigated the trend of ADRs in Calabria in 2011–2014, trying to analyze the possible entailments of the new law.</p> <p><b>Methods</b>: Quantitative and descriptive analysis of ADRs submitted by Calabrian healthcare professionals and patients to the RNF database between 2011 and 2014.</p> <p><b>Results</b>: A sharp rise in regional reporting rate was observed over study period. Calabrian Pharmacovigilance system completely fulfilled the World Health Organization gold standard for ADR reporting rate, both in 2013 and 2014. However, heterogeneity was observed regarding reporting health facilities, healthcare professionals and patients among the study years.</p> <p><b>Conclusions</b>: These findings reflect the success of the project performed in Calabria. However, this initiative should go on in the next future to obtain better and more homogeneous reporting behavior.</p