1,720,962 research outputs found
Glucagon-like peptide-1 receptor agonists are not associated with retinal adverse events in the FDA Adverse Event Reporting System
No full textObjectivesGlucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used for the treatment of type 2 diabetes. In large trials, the GLP-1RAs liraglutide and semaglutide improved cardiovascular outcomes, but semaglutide was associated with an increased risk of retinopathy progression. We herein evaluated the association between GLP-1RA and retinal adverse events (AE) in the Food and Drug Administration Adverse Event Reporting System (FAERS).Research design and methodsWe mined the FAERS between 2004q1 and 2017q1 (for a total of 9 217 555 AE reports) to analyze disproportionality and evaluate the association between GLP-1RAs and AEs involving the retina. We compared the frequency of retinal AEs among reports including GLP-1RAs and in those including other glucose-lowering medications (GLMs) as suspect or concomitant drugs.ResultsWe retrieved 114 814 reports involving GLP-1RA and 694 725 reports involving other GLMs as suspect or concomitant drugs. The cumulative frequency of retinal AEs was 2.53/1000 for reports involving GLP-1RA vs 6.62/1000 for reports involving other GLMs, with a proportional reporting ratio of 0.38 (95% CI 0.34 to 0.43; P<0.0001). Reports involving GLP-1RAs listed significantly more comorbid conditions and concomitant medications. Findings were consistent after filtering the diabetes indication irrespective of concomitant GLM, in reports including and in those not including insulin, and for the various GLP-1RAs.ConclusionsIn the FAERS there is no evidence that GLP-1RAs are associated with AEs suggestive of retinopathy progression. Despite more comorbid conditions and concomitant medications, in reports with GLP-1RA the frequency of retinal AEs was significantly lower than in reports with other GLMs.</jats:sec
Pharmacovigilance Evaluation of the Association Between DPP-4 Inhibitors and Heart Failure: Stimulated Reporting and Moderation by Drug Interactions
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DPP-4 inhibitors moderate the risk of genitourinary tract infections associated with SGLT2 inhibitors
No full textGenito-urinary tract infections (GUTI) are the most common adverse event (AE) during therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i). We evaluated whether dipeptidyl peptidase 4 inhibitors (DPP4i) moderate the risk of GUTI during therapy with SGLT2i, using two approaches. First, we screened the literature for randomized controlled trials (RCTs) directly comparing the frequency of GUTI in patients receiving a DPP4i/SGLT2i combination therapy versus those receiving a SGLT2i only. In the 5 trials we retrieved, the pooled RR for genital tract infections (GTI) in patients on a DPP4i/SGLT2i combination therapy versus those on SGLT2i alone was 0.51 (95% C.I. 0.28-0.92). Second, we found that within the Food and Drug Administration AE Reporting System (FAERS), the frequency of GUTI among reports listing both SGLT2i and DPP4i as suspect or concomitant drugs was significantly lower than among reports listing SGLT2i without DPP4i, with a proportional reporting ratio (PRR) of 0.74 (95% C.I. 0.61-0.90). In conclusion, in RCTs and in a large pharmacovigilance database, the combination with a DPP4i appears to reduce the frequency of G(U)TI associated with SGLT2i
A computational framework for similarity estimation and stimulus reconstruction of Hodgkin-Huxley neural responses
Get PDFPeriodic stimuli are known to induce chaotic oscillations in the squid giant axon for a certain range of frequencies, a behaviour modelled by the Hodgkin-Huxley equations. Inthe presence of chaotic oscillations, similarity between neural responses depends on their temporal nature as firing times and amplitudes together reflect the true dynamics of theneuron. This thesis presents a method to estimate similarity between neural responses exhibiting chaotic oscillations by using both amplitude fluctuations and firing times. It isobserved that identical stimuli have similar effect on the neural dynamics and therefore, as the temporal inputs to the neuron are identical, the occurrence of similar dynamicalpatterns result in a high estimate of similarity, which correlates with the observed temporal similarity. The information about a neural activity is encoded in a neural response and usually the underlying stimulus that triggers the activity is unknown. Thus, this thesis also presents anumerical solution to reconstruct stimuli from Hodgkin-Huxley neural responses while retrieving the neural dynamics. The stimulus is reconstructed by first retrieving themaximal conductances of the ion channels and then solving the Hodgkin-Huxley equations for the stimulus. The results show that the reconstructed stimulus is a good approximationof the original stimulus, while the retrieved the neural dynamics, which represent the voltage-dependent changes in the ion channels, help to understand the changes in neuralbiochemistry. As high non-linearity of neural dynamics renders analytical inversion of a neuron an arduous task, a numerical approach provides a local solution to the problem ofstimulus reconstruction and neural dynamics retrieval.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Spiking neurons and synaptic stimuli : determining the fidelity of coincidence-factor in neural response comparison
Get PDFSimilarity between two spike trains is generally estimated using a ‘coincidence factor’. This factor relies on counting coincidences of firing-times for spikes in a given time window. However, in cases where there are significant fluctuations in membrane voltages, this uni-dimensional view is not sufficient. Results in this paper show that a two-dimensional approach taking both firing-time and the magnitude of spikes is necessary to determine similarity between spike trains. It is observed that the difference between the lower-bound limit of faithful behaviour and the reference inter-spike interval (ISI) reduces with the increase in the ISI of the input spike train. This indicates that spike trains generated by two highly-varying currents have a high coincidence factor thus indicating higher similarity – a limitation imposed due to a one-dimensional comparison approach. These results are analysed based on the responses of a Hodgkin-Huxley neuron, where the synaptic input induces fluctuations in the output membrane voltage. The requirement for a two-dimensional analysis is further supported by a clustering algorithm which differentiates between two visually-distinct responses as opposed to coincidence-factor
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Tumor Lysis Syndrome with CD20 Monoclonal Antibodies for Chronic Lymphocytic Leukemia: Signals from the FDA Adverse Event Reporting System
No full textBackground and ObjectiveAlthough tumor lysis syndrome was reported with obinutuzumab and rituximab, the association with CD20 monoclonal antibodies for chronic lymphocytic leukemia is unclear.MethodsA disproportionality analysis was conducted to investigate the link between CD20 monoclonal antibodies and tumor lysis syndrome by accounting for known confounders and comparing with other anticancer drugs, using data from the US Food and Drug Administration Adverse Event Reporting System. Reporting odds ratios and the information component were calculated as disproportionality measures. A stepwise sensitivity analysis was conducted to test the robustness of disproportionality signals. Bradford Hill criteria were adopted to globally assess the potential causal relationship.ResultsFrom 2004 to 2022, 197, 368, 41, and 14 tumor lysis syndrome reports were detected for obinutuzumab, rituximab, ofatumumab, and alemtuzumab (CD52 monoclonal antibody), respectively. Disproportionality signals were found for the above four monoclonal antibodies when compared with other anticancer drugs. Sensitivity analyses confirmed robust disproportionality signals for obinutuzumab, rituximab, and ofatumumab. The median onset time was 4.5, 1.5, and 2.5 days for rituximab, obinutuzumab, and ofatumumab, respectively. A potential causal relationship was fulfilled by assessing Bradford Hill criteria.ConclusionsThis pharmacovigilance study on the FDA Adverse Event Reporting System detected a plausible association between CD20 monoclonal antibodies (but not CD52) and tumor lysis syndrome by assessing the adapted Bradford Hill criteria. Urgent clarification of drug- and patient-related risk factors is needed through large comparative population-based studies
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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