Detecting associations between behavioral addictions and dopamine agonists in the Food & Drug Administration's Adverse Event database

Abstract Background/Aims Studies have reported higher prevalences of four behavioral addictions (binge eating, compulsive shopping, hypersexuality, and pathological gambling) in dopamine agonist-treated Parkinson's disease relative to non-dopamine agonist-treated Parkinson's. However, recent case-control and epidemiological studies suggest that prevalences of behavioral addictions in dopamine agonist-treated Parkinson's may be similar to background population rates. This study tests that hypothesis by examining the FDA Adverse Event Reporting System (FAERS) for evidence of these associations, taking into account the potential impact of publicity on reporting rates. Methods FAERS reports in 2004 (pre-publicity for all but pathological gambling) and 2007 (post-publicity for all four behaviors) were analyzed. A threshold consisting of ≥3 cases, proportional reporting ratio ≥2, and χ2 with Yates' correction ≥4 was used to detect signals (drug-associated adverse reactions) involving any of five dopamine agonists and any of four behavioral addictions. Results No reports containing compulsive shopping and no signal for binge eating and dopamine agonists were found in either year. A weak signal was found for hypersexuality in 2004, with a stronger signal in 2007. A robust signal was found for pathological gambling in 2004, with a more robust signal in 2007. Discussion/Conclusions These results suggest that publicity may increase reporting rates in the FAERS. Findings for binge eating, compulsive shopping, and hypersexuality suggest that prevalences of these behaviors among those treated with dopamine agonists may be similar to background population rates and thus may not reflect an adverse safety signal. Further investigation of the relationship between dopamine agonists and behavioral addictions is warranted

Publicity and reports of behavioral addictions associated with dopamine agonists

Background The development of behavioral addictions (BAs) in association with dopamine agonists (DAs, commonly used to treat Parkinson’s disease) has been reported. A recent report presented data that these associations are evident in the US Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS), a database containing information on adverse drug event and medication error reports submitted to the FDA. However, given that vulnerability to publicity-stimulated reporting is a potential limitation of spontaneous reporting systems like the FAERS, the potential impact of publicity on reporting in this case remains unclear. Method and aims To investigate the potential impact of publicity on FAERS reporting of BAs in association with DAs (BAs w/DAs) as presented by Moore, Glenmullen, and Mattison (2014), news stories covering a BA/DA association were identified and compared with BA w/DA and other reporting data in the FAERS. Results Fluctuations in the growth of BA w/DA reporting to the FAERS between 2003 and 2012 appear to coincide with multiple periods of intensive media coverage of a BA/DA association, a pattern that is not evident in other reporting data in the FAERS. Discussion/Conclusions Publicity may stimulate reporting of adverse events and premature dismissal of the potential influence of publicity on reporting may lead to mistaking an increased risk of an adverse event being reported for an increased risk of an adverse event occurring

Pain interference, gambling problem severity, and psychiatric disorders among a nationally representative sample of adults

Background and aims: A paucity of studies has examined the association between gambling and pain interference. We examined differences in the associations of gambling problem severity and psychiatric disorders among a nationally representative sample of adults with varying levels of pain interference. Methods: Chi-square tests and logistic regression analyses were performed on National Epidemiologic Survey on Alcohol and Related Conditions data from 41,987 adult respondents (48% men; 52% women), who were categorized according to two levels of pain interference (i.e., no or low pain interference [NLPI] or moderate or severe pain interference [MSPI]) and three levels of gambling problem severity (i.e., non-gamblers or low-frequency gamblers [NG], low-risk or at-risk gamblers [LRG], and problem or pathological gamblers [PPG]). Results: MSPI respondents exhibited higher rates of PPG than NLPI respondents. Categories of Axis I disorders and clusters of mood, anxiety and substance-use disorders showed similarly strong associations with problem-gambling severity in MSPI and NLPI groups. Similarly strong associations between Axis II disorders (and each cluster — A, B and C) and problem-gambling severity were also observed in MSPI and NLPI groups. Exploratory analyses suggested potentially stronger relationships between PPG and dysthymia, panic disorder, and dependent personality disorder and LRG and specific phobia in NLPI compared to MSPI respondents. Discussion and conclusions: While MSPI is associated with PPG, largely similar patterns of associations across pain-interference levels were observed between problem-gambling severity and Axis I and Axis II psychiatric disorders

Use of biological drugs in patients with psoriasis and psoriatic arthritis in italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of differentanti-TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsApatients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 wasanalyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug sur-vival rate and probability of maintaining PASI response were evaluated. The impact of dependentvariables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients wereincluded, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumabfollowed by etanercept and infliximab in PsO and PsA patients. The probability of maintainingPASI response was significantly higher for adalimumab followed by infliximab. For PsO patients,the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 8.1; 95% CI: 4.2–15.6,p<.001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3,p<.001) vs. adalimumab. Likewise, for PsApatients the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 2.3; 95% CI:1.4–3.8,p5.01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1,p5.018) vs. adalimumab. Adalimumabcould be the best therapeutic option over other anti-TNF agents for the treatment of PsO and PsApatients

A fragment-based virtual screening approach to identify e-cadherin lingands

Cadherins are calcium-dependent cell-cell adhesion proteins which are overexpressed in several solid tumors [1]. They contain an extracellular region consisting of five immunoglobulin-like domains that extend from the cell surface. Recent crystal structures have shown that classical cadherins dimerize through a \u2018strand-swap\u2019 trans-adhesive interface involving the N-terminal EC1 domains of two cadherins on adjacent cells [2, 3]. Despite a growing interest in the field, the rational design of small ligands targeting cadherins is still in a very early stage. Recently, our group set up a docking protocol (Glide v 5.7) to rationally design peptidomimetic ligands mimicking the N- and E-cadherin adhesive homodimer interface. Accordingly, the first mimics based on the tetrapeptide sequence Asp1-Trp2-Val3-Ile4 (DWVI) of the N-terminal adhesion arm were achieved and proved to inhibit the adhesion of epithelial ovarian cancer cells with millimolar potency [4]. Herein, a fragment-based virtual screening approach was applied to identify novel chemical entries targeting the DWVI binding site. Commercially available Maybridge and Life chemicals collections were used. The most promising fragments identified by the docking calculations were purchased and their binding to E-cadherin was evaluated by means of STD (Saturation Transfer Difference) NMR experiments. Acknowledgements: We thank MIUR (PRIN 2015 project 20157WW5EH) for financial support. ____ [1] G. Berx, F. van Roy, Cold Spring Harbor Perspectives in Biology 2009, 1, a003129. [2] D. Leckband, S. Sivasankar, Curr. Opin. Cell Biol. 2012, 24, 620-627. [3] J. Vendome, K. Felsovalyi, H. Song, Z. Yang, X. Jin, J. Brasch, O. J. Harrison, G. Ahlsen, F. Bahna, A. Kaczynska, P. S. Katsamba, D. Edmond, W. L. Hubbell, L. Shapiro, B. Honig, PNAS 2014, 111, E4175-E4184. [4] F. Doro, C. Colombo, C. Alberti, D. Arosio, L. Belvisi, C. Casagrande, R. Fanelli, L. Manzoni, E. Parisini, U. Piarulli, E. Luison, M. Figini, A. Tomassetti, M. Civera, Org. Biomol. Chem. 2015, 13, 2570-2573

Dynamic titanium prosthesis based on 3D-printed replica for chest wall resection and reconstruction

3D-printing technologies can assist the surgical planning and prosthesis engineering for the management of extended chest wall resection. Different types of prosthesis have been utilized over time, but some concerns remain about their impact on the respiratory function. Here we present a new kind of 3D-printed titanium prosthesis designed to be either strong and flexible. The prosthesis was created on a 1:1 3D-printed anatomic replica of the chest, used to delineate surgical margins and to define the reconstructive requirements

NMR interaction studies of Neu5Ac-&#945;-(2,6)-Gal-&#946;-(1-4)-GlcNAc with influenza-virus hemagglutinin expressed in transfected human cells

The emergence of escape-mutants of influenza hemagglutinin (HA) following vaccination compels the yearly re-formulation of flu vaccines. Since binding the sialic acid receptor remains in all cases essential for infection, small-molecule inhibitors of HA binding to sialic acid could be interesting therapeutic complements or alternatives to immuno-prophylaxis in the control of flu epidemics. In this work, we made use of NMR spectroscopy to study the interaction between a derivative of sialic acid (the Neu5Ac-\u3b1-(2,6)-Gal-\u3b2-(1-4)-GlcNAc trisaccharide) and HAs (H1 and H5) from human and avian strains of influenza virus, directly expressed on the surface of stable transfected 293 T human cells. The HAs were shown to retain their native trimeric conformation and binding properties. Exploiting the magnetization transfer between the proteins and the ligand, we obtained evidence of the binding event and mapped the (non-identical) sugar epitopes recognized by the two HA species. The rapid and reliable method for screening sialic acid-related HA ligands we have developed could yield useful information for an efficient drug design

Heat Conduction and Microconvection in Nanofluids: Comparison between Theoretical Models and Experimental Results

A nanofluid is a suspension consisting of a uniform distribution of nanoparticles in a base fluid, generally a liquid. Nanofluid can be used as a working fluid in heat exchangers to dissipate heat in the automotive, solar, aviation, aerospace industries. There are numerous physical phenomena that affect heat conduction in nanofluids: clusters, the formation of adsorbate nanolayers, scattering of phonons at the solid–liquid interface, Brownian motion of the base fluid and thermophoresis in the nanofluids. The predominance of one physical phenomenon over another depends on various parameters, such as temperature, size and volume fraction of the nanoparticles. Therefore, it is very difficult to develop a theoretical model for estimating the effective thermal conductivity of nanofluids that considers all these phenomena and is accurate for each value of the influencing parameters. The aim of this study is to promote a way to find the conditions (temperature, volume fraction) under which certain phenomena prevail over others in order to obtain a quantitative tool for the selection of the theoretical model to be used. For this purpose, two sets (SET-I, SET-II) of experimental data were analyzed; one was obtained from the literature, and the other was obtained through experimental tests. Different theoretical models, each considering some physical phenomena and neglecting others, were used to explain the experimental results. The results of the paper show that clusters, the formation of the adsorbate nanolayer and the scattering of phonons at the solid–liquid interface are the main phenomena to be considered when ϕ = 1 ÷ 3%. Instead, at a temperature of 50 ◦C and in the volume fraction range (0.04–0.22%), microconvection prevails over other phenomen