Methods to reduce medication errors in a clinical trial of an investigational parenteral medication

AbstractThere are few evidence-based guidelines to inform optimal design of complex clinical trials, such as those assessing the safety and efficacy of intravenous drugs administered daily with infusion times over many hours per day and treatment durations that may span years. This study is a retrospective review of inpatient administration deviation reports for an investigational drug that is administered daily with infusion times of 8–24 h, and variable treatment durations for each patient. We report study design modifications made in 2007–2008 aimed at minimizing deviations from an investigational drug infusion protocol approved by an institutional review board and the United States Food and Drug Administration. Modifications were specifically aimed at minimizing errors of infusion rate, incorrect dose, incorrect patient, or wrong drug administered. We found that the rate of these types of administration errors of the study drug was significantly decreased following adoption of the specific study design changes. This report provides guidance in the design of clinical trials testing the safety and efficacy of study drugs administered via intravenous infusion in an inpatient setting so as to minimize drug administration protocol deviations and optimize patient safety

Monitoring Repair of UV-Induced 6-4-Photoproducts with a Purified DDB2 Protein Complex

Because cells are constantly subjected to DNA damaging insults, DNA repair pathways are critical for genome integrity [1]. DNA damage recognition protein complexes (DRCs) recognize DNA damage and initiate DNA repair. The DNA-Damage Binding protein 2 (DDB2) complex is a DRC that initiates nucleotide excision repair (NER) of DNA damage caused by ultraviolet light (UV) [2]-[4]. Using a purified DDB2 DRC, we created a probe ("DDB2 proteo-probe") that hybridizes to nuclei of cells irradiated with UV and not to cells exposed to other genotoxins. The DDB2 proteo-probe recognized UV-irradiated DNA in classical laboratory assays, including cyto- and histo-chemistry, flow cytometry, and slot-blotting. When immobilized, the proteo-probe also bound soluble UV-irradiated DNA in ELISA-like and DNA pull-down assays. In vitro, the DDB2 proteo-probe preferentially bound 6-4-photoproducts [(6-4)PPs] rather than cyclobutane pyrimidine dimers (CPDs). We followed UV-damage repair by cyto-chemistry in cells fixed at different time after UV irradiation, using either the DDB2 proteo-probe or antibodies against CPDs, or (6-4)PPs. The signals obtained with the DDB2 proteo-probe and with the antibody against (6-4)PPs decreased in a nearly identical manner. Since (6-4)PPs are repaired only by nucleotide excision repair (NER), our results strongly suggest the DDB2 proteo-probe hybridizes to DNA containing (6-4)PPs and allows monitoring of their removal during NER. We discuss the general use of purified DRCs as probes, in lieu of antibodies, to recognize and monitor DNA damage and repair

Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis

Distinguishing malignant cells from non-neoplastic ones is a major challenge in triple-negative breast cancer (TNBC) treatment. Here, we developed a complementary targeting strategy that uses precisely matched, multivalent ligand-receptor interactions to recognize and target TNBC tumors at the primary site and metastatic lesions. We screened a panel of cancer cell surface markers and identified intercellular adhesion molecule–1 (ICAM1) and epithelial growth factor receptor (EGFR) as optimal candidates for TNBC complementary targeting. We engineered a dual complementary liposome (DCL) that precisely complements the molecular ratio and organization of ICAM1 and EGFR specific to TNBC cell surfaces. Our in vitro mechanistic studies demonstrated that DCLs, compared to single-targeting liposomes, exhibited increased binding, enhanced internalization, and decreased receptor signaling. DCLs consistently exhibited substantially increased tumor targeting activity and antitumor efficacy in orthotopic and lung metastasis models, indicating that DCLs are a platform technology for the design of personalized nanomedicines for TNBC

Risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy: population based retrospective cohort study.

OBJECTIVE: To assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy. DESIGN: Population based retrospective cohort study. SETTING: Ontario, Canada, 1 May to 31 December 2021. PARTICIPANTS: All liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g. MAIN OUTCOME MEASURES: Using Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (<32 weeks), small for gestational age at birth (<10th centile), and stillbirth. Vaccination against covid-19 was treated as a time varying exposure in the outcome specific risk window, and propensity score weighting was used to adjust hazard ratios for potential confounding. RESULTS: Among 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy-42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinated v 6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7% v 4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59% v 0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1% v 9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25% v 0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy. CONCLUSION: The findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth

The cognitive decision space of trust: An exploratory study of image trustworthiness and the propensity to deceive

In an age where any digital image can be manipulated, studying how and why people trust images as well as how likely people are to endorse deceptive images has become a topic of increasing importance. But, how is it human beings decide whether they trust and image, or not? This article attempts to shed light on the cognitive decision space of trust by means of two experiments. The goal of the first experiment was to induce the dimensions underpinning decisions of trust in relation to images. The goal of the second experiment was to investigate the propensity for subjects to deceive with images in conditions of both high and low levels of deception. The first experiment revealed four dimensions that determined the level of trust in an image: the features of the image, its content, its source, and the participants’ own background knowledge. The second experiment suggests that there is propensity for human subjects to deceive with images

Do you trust this image? Exploring the subjectivity of image trustworthiness from a cognitive perspective

Introduction In an age where any digital image can be manipulated, studying how and why people trust images as well as how likely people are to endorse deceptive images has become a topic of increasing importance. But, how is it human beings decide whether they trust and image? The goal of this study was to identify intersubjective cognitive dimensions which underpin decisions of trust in relation to images. Method This article attempts to shed light on the cognitive decision space of trust by means of a substantial crowd sourced empirical study Analysis Qualitative data was coded using an axial coding method, with focus placed on themes of the features bearing on decisions of trust. Results The study reveals four dimensions: the features of the image, its content, its source, and the participants’ own background knowledge. The study also reveals a surprising cognitive effect: In some cases participants confounded the decision of the trustworthiness of an image, with a decision of whether they trust the subject portrayed in the image. Conclusions It cannot be assumed that digital images will necessarily or automatically be trusted by those viewing these artefacts. There are many socio-cognitive factors in play and a reliable source alone does not consistently determine trustworthiness for users. This article aims to raise awareness in the cultural heritage sector of the need to take cognitive science perspectives into account

Legislative Documents

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