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EFSA Journal. European Food Safety... Oct 2023EFSA Strategy 2027 outlines the need for fit-for-purpose protocols for EFSA generic scientific assessments to aid in delivering trustworthy scientific advice. This EFSA...
EFSA Strategy 2027 outlines the need for fit-for-purpose protocols for EFSA generic scientific assessments to aid in delivering trustworthy scientific advice. This EFSA Scientific Committee guidance document helps address this need by providing a harmonised and flexible framework for developing protocols for EFSA generic assessments. The guidance replaces the 'Draft framework for protocol development for EFSA's scientific assessments' published in 2020. The two main steps in protocol development are described. The first is problem formulation, which illustrates the objectives of the assessment. Here a new approach to translating the mandated Terms of Reference into scientifically answerable assessment questions and sub-questions is proposed: the 'APRIO' paradigm (Agent, Pathway, Receptor, Intervention and Output). Owing to its cross-cutting nature, this paradigm is considered adaptable and broadly applicable within and across the various EFSA domains and, if applied using the definitions given in this guidance, is expected to help harmonise the problem formulation process and outputs and foster consistency in protocol development. APRIO may also overcome the difficulty of implementing some existing frameworks across the multiple EFSA disciplines, e.g. the PICO/PECO approach (Population, Intervention/Exposure, Comparator, Outcome). Therefore, although not mandatory, APRIO is recommended. The second step in protocol development is the specification of the evidence needs and the methods that will be applied for answering the assessment questions and sub-questions, including uncertainty analysis. Five possible approaches to answering individual (sub-)questions are outlined: using evidence from scientific literature and study reports; using data from databases other than bibliographic; using expert judgement informally collected or elicited via semi-formal or formal expert knowledge elicitation processes; using mathematical/statistical models; and - not covered in this guidance - generating empirical evidence . The guidance is complemented by a standalone 'template' for EFSA protocols that guides the users step by step through the process of planning an EFSA scientific assessment.
PubMed: 37908452
DOI: 10.2903/j.efsa.2023.8312 -
BMJ Open Quality Oct 2023An institution-wide protocol for uncomplicated acute appendicitis was created to improve compliance with best practices between the emergency department (ED), radiology...
INTRODUCTION
An institution-wide protocol for uncomplicated acute appendicitis was created to improve compliance with best practices between the emergency department (ED), radiology and surgery. Awareness of the protocol was spread with the publication of a smartphone application and communication to clinical leadership. On interim review of quality metrics, poor protocol adherence in diagnostic imaging and antimicrobial stewardship was observed. The authors hypothesised that two further simple interventions would result in more efficient radiographic diagnosis and antimicrobial administration.
MATERIALS AND METHODS
Surgery residents received targeted in-person education on the appropriate antibiotic choices and diagnostic imaging in the protocol. Signs were placed in the emergency and radiology work areas, immediately adjacent to provider workstations highlighting the preferred imaging for patients with suspected appendicitis and the preferred antibiotic choices for those with proven appendicitis. Protocol adherence was compared before and after each intervention.
RESULTS
Targeted education was associated with improved antibiotic stewardship within the surgical department from 30% to 91% protocol adherence before/after intervention (p<0.005). Visible signs in the ED were associated with expedited antimicrobial administration from 50% to 90% of patients receiving antibiotics in the ED prior to being brought to the operating room before/after intervention (p<0.005). Diagnostic imaging after the placement of signs showed improved protocol adherence from 35% to 75% (p<0.005).
CONCLUSION
This study demonstrates that smartphone-based applications and communication among clinical leadership achieved suboptimal adherence to an institutional protocol. Targeted in-person education reinforcement and visible signage immediately adjacent to provider workstations were associated with significantly increased adherence. This type of initiative can be used in other aspects of acute care general surgery to further improve quality of care and hospital efficiency.
Topics: Humans; Appendicitis; Anti-Bacterial Agents
PubMed: 37879672
DOI: 10.1136/bmjoq-2023-002327 -
BMC Cancer Oct 2023There are no standard third-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC). Trametinib in combination with hydroxychloroquine (HCQ) or...
BACKGROUND
There are no standard third-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC). Trametinib in combination with hydroxychloroquine (HCQ) or CDK4/6 inhibitors for pancreatic adenocarcinoma showed promising efficacy in preclinical studies. However, the regimens have not been well examined in patients with mPDAC.
METHODS
Patients with mPDAC who received the combination of trametinib and HCQ or CDK4/6 inhibitors as third- or later-line therapy were reviewed. The efficacy and prognosis were further analyzed.
RESULTS
A total of 13 mPDAC patients were enrolled, of whom 8 and 5 patients were treated with trametinib plus HCQ or a CDK4/6 inhibitor (palbociclib or abemaciclib), respectively. All enrolled patients had either KRAS G12D or G12V mutations and had received a median of 3 prior lines of therapy (range, 2-6). The median trametinib treatment duration was 1.4 months. Of the 10 patients with measurable disease, only 1 patient achieved stable disease, and the remaining patients had progressive disease. Moreover, in patients treated with trametinib plus HCQ and a CDK4/6 inhibitor, the median progression-free survival was 2.0 and 2.8 months, respectively, and the median overall survival was 4.2 and 4.7 months, respectively. Moreover, 5 (50%) patients experienced grade 3-4 adverse events in 10 patients with available safety data.
CONCLUSIONS
The combination of trametinib and HCQ or CDK4/6 inhibitors may not be an effective later-line treatment for mPDAC, and the current preliminary findings need to be confirmed by other studies with larger sample sizes.
Topics: Humans; Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Therapy, Combination; Hydroxychloroquine; Pancreatic Neoplasms; Protein Kinase Inhibitors
PubMed: 37817078
DOI: 10.1186/s12885-023-11464-3 -
Revista Da Escola de Enfermagem Da U S P 2023To evaluate the effectiveness of acupuncture and auriculotherapy protocol in relieving chemotherapy-induced nausea and vomiting in cancer patients compared to the...
OBJECTIVE
To evaluate the effectiveness of acupuncture and auriculotherapy protocol in relieving chemotherapy-induced nausea and vomiting in cancer patients compared to the antiemetic protocol.
METHOD
Pilot study of a pragmatic two-arm clinical trial: an acupuncture group received systemic acupuncture, auriculotherapy, and antiemetic protocol; a control group used antiemetic protocol. The sample consisted of 42 patients with cancer of the gastrointestinal system or multiple myeloma. The outcome was assessed using the Chemotherapy-Induced Nausea and Vomiting Assessment Tool and the patient's diary.
RESULTS
There was no statistically significant difference between groups according to the assessment of the patient's diary and the Assessment Tool of chemotherapy-induced nausea and vomiting. The patients were 60 years old on average and the groups were homogeneous, except for marital status. In the diary, there was no statistical difference between groups and sessions for days of nausea (p = 0.873) and vomiting episodes (p = 0.993).
CONCLUSION
The protocol of acupuncture and auriculotherapy as a complementary treatment of chemotherapy-induced nausea and vomiting was ineffective, considering the limitations of the study.
Topics: Humans; Middle Aged; Pilot Projects; Antiemetics; Vomiting; Acupuncture Therapy; Nausea; Auriculotherapy; Neoplasms; Antineoplastic Agents
PubMed: 37930237
DOI: 10.1590/1980-220X-REEUSP-2023-0191en -
European Radiology Nov 2023Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [F]FDG PET/MRI to...
OBJECTIVES
Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [F]FDG PET/MRI to avoid adverse effects and save time and costs during examination.
METHODS
A total of 105 [F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin's Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests.
RESULTS
In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2.
CONCLUSIONS
The use of MRI contrast agents in [F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent-free [F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients.
CLINICAL RELEVANCE STATEMENT
This study gives a scientific baseline switching to a contrast agent-free [F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients.
KEY POINTS
• No additional diagnostic benefit of MRI contrast agents at [F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging • Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast-free [F]FDG PET/MRI.
Topics: Humans; Child; Fluorodeoxyglucose F18; Contrast Media; Neoplasm Staging; Magnetic Resonance Imaging; Lymphoma; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 37338559
DOI: 10.1007/s00330-023-09840-5 -
STAR Protocols Dec 2023Agent-based models are composed of individual agents coded for traits, such as cooperation and cheating, that interact in a virtual world based on defined rules. Here,...
Agent-based models are composed of individual agents coded for traits, such as cooperation and cheating, that interact in a virtual world based on defined rules. Here, we describe the use of an agent-based model of homologous recombination in bacteria playing a public goods game. We describe steps for software installation, setting model parameters, running and testing models, and visualization and statistical analysis. This protocol is useful in analyses of horizontal gene transfer, bacterial sociobiology, and game theory. For complete details on the use and execution of this protocol, please refer to Lee et al..
Topics: Game Theory; Bacteria
PubMed: 37980566
DOI: 10.1016/j.xpro.2023.102733 -
Current Protocols Nov 2023Replication timing is significantly correlated with gene expression and chromatin organization, changes dynamically during cell differentiation, and is altered in...
Replication timing is significantly correlated with gene expression and chromatin organization, changes dynamically during cell differentiation, and is altered in diseased states. Genome-wide analysis of replication timing is performed in actively replicating cells by Repli-seq. Current methods for Repli-seq require cells to be fixed in large numbers. This is a barrier for sample types that are sensitive to fixation or are in very limited numbers. In this article, we outline optimized methods to process live cells and intact nuclei for Repli-seq. Our protocol enables the processing of a smaller number of cells per sample and reduces processing time and sample loss while obtaining high-quality data. Further, for samples that tend to form clumps and are difficult to dissociate into a single-cell suspension, we also outline methods for isolation, staining, and processing of nuclei for Repli-seq. The Repli-seq data obtained from live cells and intact nuclei are comparable to those obtained from the standard protocols. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Live cell isolation and staining Alternate Protocol: Nuclei isolation and staining.
Topics: Coloring Agents; Cell Nucleus; DNA Replication Timing; Cell Separation; Genome
PubMed: 38009262
DOI: 10.1002/cpz1.945 -
Cancer Reports (Hoboken, N.J.) Sep 2023Choosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized... (Review)
Review
BACKGROUND
Choosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.
RECENT FINDINGS
Pharmacogenomics, the study of how an individual's genes impact the processing and action of a drug, can optimize drug responsiveness and reduce toxicities by creating a customized medication regimen. However, these differences are rarely considered in the initial determination of standardized chemotherapeutic protocols and treatment algorithms. Because pharmacoethnicity is influenced by both genetic and nongenetic variables, clinical data highlighting disparities in the frequency of polymorphisms between different ethnicities is steadily growing. Recent data suggests that ethnic variations in the expression of allelic variants may result in different pharmacokinetic properties of the anti-cancer medication. In this article, the clinical outcomes of various chemotherapy classes in patients of different ethnicities were reviewed.
CONCLUSION
Genetic and nongenetic variables contribute to the interindividual variability in response to chemotherapeutic drugs. Considering pharmacoethnicity in the initial determination of standard chemotherapeutic protocols and treatment algorithms can lead to better clinical outcomes of patients of different ethnicities.
Topics: Humans; Neoplasms; Polymorphism, Genetic
PubMed: 37150853
DOI: 10.1002/cnr2.1830 -
Journal of Molecular Graphics &... Jul 2023An in silico consensus molecular docking approach and in vitro evaluations were adopted in the present study to explore a dataset of FDA-approved drugs as novel... (Review)
Review
An in silico consensus molecular docking approach and in vitro evaluations were adopted in the present study to explore a dataset of FDA-approved drugs as novel multitarget MAO-B/AChE agents in the treatment of Alzheimer's disease (AD). GOLD 5.3 and Glide were employed in the virtual assessments and consensus superimpositions of the obtained poses were applied to increase the reliability of the docking protocols. Furthermore, the top ranked molecules were subjected to binding free energy calculations using MM/GBSA, Induced fit docking (IFD) simulations, and a literature review. Consequently, the top four multitarget drugs were examined for their in vitro MAO-B and AChE inhibition effects. The consensus molecular docking identified Dolutegravir, Rebamipide, Loracarbef and Diflunisal as potential multitarget drugs. The biological data demonstrated that most of the docking scores were in good correlation with the in vitro experiments, however the theoretical simulations in the active site of MAO-B identified two false-positives - Rebamipide and Diflunisal. Dolutegravir and Loracarbef were accessed as active MAO-B inhibitors, while Dolutegravir, Rebamapide and Diflunisal as potential AChE inhibitors. The antiretroviral agent Dolutegravir exhibited the most potent multitarget activity - 41% inhibition of MAO-B (1 μM) and 68% inhibition of AChE (10 μM). Visualizations of the intermolecular interactions of Dolutegravir in the active sites of MAO-B and AChE revealed the formation of several stable hydrogen bonds. Overall, Dolutegravir was identified as a potential anti-AD drug, however further in vivo evaluations should be considered.
Topics: Humans; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Alzheimer Disease; Molecular Docking Simulation; Diflunisal; Drug Repositioning; Reproducibility of Results; Cholinesterase Inhibitors; Acetylcholinesterase
PubMed: 37087882
DOI: 10.1016/j.jmgm.2023.108471 -
BMJ Open Nov 2023Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses,...
INTRODUCTION
Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation.
METHODS AND ANALYSIS
This is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg min and titrated per protocol. The primary outcome is the dose of norepinephrine required to maintain a mean arterial pressure ≥65 mm Hg. Secondary outcomes include vasopressin or epinephrine requirement and duration of hypotension. Safety outcomes include incidence of thromboembolism within 48 hours of the end of surgery and severe hypertension. An intention-to-treat analysis will be performed for all randomised subjects receiving the study drug. The total dose of norepinephrine will be compared between the two arms by a one-tailed Mann-Whitney U test.
ETHICS AND DISSEMINATION
The trial protocol was approved by the local Institutional Review Board (#20-30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
ClinicalTrials.govNCT04901169.
Topics: Adult; Humans; Angiotensin II; Liver Transplantation; End Stage Liver Disease; Severity of Illness Index; Living Donors; Vasoconstrictor Agents; Hypotension; Norepinephrine; Double-Blind Method; Catecholamines; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37984940
DOI: 10.1136/bmjopen-2023-078713