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A 42-year-old male patient visited the outpatient department for follow-up with a history of respiratory tract infection and diabetes mellitus. His main symptom was peeling of his epidermal layer of skin, and bullous fixed drug eruption on the lower and upper limbs and bank region of the body. Following assessment, the patient was prescribed levothyroxine, hydroxychloroquine, levofloxacin, and a combination of sulfamethoxazole-trimethoprim. On assessing causality of the adverse drug reaction (ADR), different ADR assessment scales such as the WHO-UMC Scale, Naranjo Scale, and Hartwig's Severity Assessment Scale were used, and the ADR was found by these scales to be 'likely', 'moderate', and 'probable', respectively. It was found that ADRs such as bullous fixed drug eruptions are not fatal but can cause patient anxiety and a reduced quality of life. This case report will help physicians and clinicians to become aware and vigilant about the ADR caused by levofloxacin, facilitating its early detection and management.
The context for the implementation of evidence-based psychological treatments (EBPTs) often differs from the context in which the treatment was developed, which necessitates adaptations. In this systematic review we build on, and add to, prior approaches by examining the method used to guide such adaptations. In particular, we sought to elucidate the extent to which an empirical process is used.
We focused on publications describing adaptations made to EBPTs for adults diagnosed with a mental illness. We searched PubMed, PsycINFO, Embase and Web of Science from database inception to July 2018. Two raters independently coded the articles for the method used to conduct the adaptation, the reason for and nature of the adaptation, and who made the adaptation.
The search produced 20 194 citations, which yielded 152 articles after screening. The most commonly used methods for planned adaptations were literature review (57.7%), clinical intuition (47.0%) and theory (38.9%). KRX-0401 chemical structure The use of data from stakeholder interviews ranked fourth (21.5%) and the use of other types of data (eg, pilot study, experiment, survey, interview) ranked last at fifth (12.1%). Few publications reporting ad hoc adaptations were identified (n=3).
This review highlights a need to (a) educate providers and researchers to carefully consider the methods used for the treatment adaptation process, and to use empirical methods where possible and where appropriate, (b) improve the quality of reporting of stakeholder interviews and (c) develop reporting standards that articulate optimal methods for conducting treatment adaptations.
This review highlights a need to (a) educate providers and researchers to carefully consider the methods used for the treatment adaptation process, and to use empirical methods where possible and where appropriate, (b) improve the quality of reporting of stakeholder interviews and (c) develop reporting standards that articulate optimal methods for conducting treatment adaptations.Immunotherapy of immunologically cold solid tumors may require multiple agents to engage immune effector cells, expand effector populations and activities, and enable immune responses in the tumor microenvironment (TME). To target these distinct phenomena, we strategically chose five clinical-stage immuno-oncology agents, namely, (i) a tumor antigen-targeting adenovirus-based vaccine (Ad-CEA) and an IL15 superagonist (N-803) to activate tumor-specific T cells, (ii) OX40 and GITR agonists to expand and enhance the activated effector populations, and (iii) an IDO inhibitor (IDOi) to enable effector-cell activity in the TME. Flow cytometry, T-cell receptor (TCR) sequencing, and RNA-sequencing (RNA-seq) analyses showed that in the CEA-transgenic murine colon carcinoma (MC38-CEA) tumor model, Ad-CEA + N-803 combination therapy resulted in immune-mediated antitumor effects and promoted the expression of costimulatory molecules on immune subsets, OX40 and GITR, and the inhibitory molecule IDO. Treatment with Ad-CEA + N-803 + OX40 + GITR + IDOi, termed the pentatherapy regimen, resulted in the greatest inhibition of tumor growth and protection from tumor rechallenge without toxicity. Monotherapy with any of the agents had little to no antitumor activity, whereas combining two, three, or four agents had minimal antitumor effects. Immune analyses demonstrated that the pentatherapy combination induced CD4+ and CD8+ T-cell activity in the periphery and tumor, and antitumor activity associated with decreased regulatory T-cell (Treg) immunosuppression in the TME. The pentatherapy combination also inhibited tumor growth and metastatic formation in 4T1 and LL2-CEA murine tumor models. This study provides the rationale for the combination of multimodal immunotherapy agents to engage, enhance, and enable adaptive antitumor immunity.Research on memory reconsolidation has been booming in the last two decades, with numerous high-impact publications reporting promising amnestic interventions in rodents and humans. However, our own recently-published failed replication attempts of reactivation-dependent amnesia for fear memories in rats suggest that such amnestic effects are not always readily found and that they depend on subtle and possibly uncontrollable parameters. The discrepancy between our observations and published studies in rodents suggests that the literature in this field might be biased. The aim of the current study was to gauge the presence of publication bias in a well-delineated part of the reconsolidation literature. To this end, we performed a systematic review of the literature on reactivation-dependent amnesia for contextual fear memories in rodents, followed by a statistical assessment of publication bias in this sample. In addition, relevant researchers were contacted for unpublished results, which were included in the current analyses. The obtained results support the presence of publication bias, suggesting that the literature provides an overly optimistic overall estimate of the size and reproducibility of amnestic effects. Reactivation-dependent amnesia for contextual fear memories in rodents is thus less robust than what is projected by the literature. The moderate success of clinical studies may be in line with this conclusion, rather than reflecting translational issues. For the field to evolve, replication and non-biased publication of obtained results are essential. A set of tools that can create opportunities to increase transparency, reproducibility and credibility of research findings is provided.
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