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The Journal of Antimicrobial... Jan 2017Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous...
OBJECTIVES
Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous antibiotics used or fastidious pathogens) are available. We performed this study to evaluate the effectiveness of our therapeutic protocol in BCNE, based on compliance with the protocol, outcome and 1 year mortality.
PATIENTS AND METHODS
We collected prospectively and analysed retrospectively cases of BCNE between 2002 and 2014, using a simplified and standardized protocol developed by our multidisciplinary team. We apply two kinds of protocols to treat BCNE, which include only four intravenous antimicrobial agents: amoxicillin, vancomycin, gentamicin and amphotericin B.
RESULTS
We had 177 patients with definite BCNE. There were 154 (87.0%) patients treated with both appropriate antimicrobial agents and appropriate duration of treatment. We analysed the causes of inappropriate treatment in 13 (7.3%) cases and inappropriate duration in 10 (5.6%) cases. The treatment changes were justified in all cases except one of discharge against medical advice. The fatality rate was 5.1% (nine cases) and all deaths occurred in the group of patients who were treated with appropriate treatment; however, four deaths were not attributable to empirical treatment failure. Concerning the other deaths, the lack of surgical management, in association with empirical treatment, could explain our protocol's failure, such as poorly tolerated surgery.
CONCLUSIONS
Our protocol is efficient and our mortality rate was low, compared with the literature review. This may result from a strategy that uses a sampling procedure and a standardized protocol at the same time.
Topics: Administration, Intravenous; Aged; Anti-Infective Agents; Endocarditis; Female; Humans; Male; Prospective Studies; Retrospective Studies; Survival Analysis; Treatment Outcome
PubMed: 27678286
DOI: 10.1093/jac/dkw362 -
Autonomous Agents and Multi-agent... 2021We propose a formalism to model and reason about reconfigurable multi-agent systems. In our formalism, agents interact and communicate in different modes so that they...
We propose a formalism to model and reason about reconfigurable multi-agent systems. In our formalism, agents interact and communicate in different modes so that they can pursue joint tasks; agents may dynamically synchronize, exchange data, adapt their behaviour, and reconfigure their communication interfaces. Inspired by existing multi-robot systems, we represent a system as a set of agents (each with local state), executing independently and only influence each other by means of message exchange. Agents are able to sense their local states and partially their surroundings. We extend ltl to be able to reason explicitly about the intentions of agents in the interaction and their communication protocols. We also study the complexity of satisfiability and model-checking of this extension.
PubMed: 34776761
DOI: 10.1007/s10458-021-09521-x -
International Journal of Molecular... Nov 2021Corneal cryopreservation can partially solve the worldwide concern regarding donor cornea shortage for keratoplasties. In this study, human corneas were cryopreserved...
Corneal cryopreservation can partially solve the worldwide concern regarding donor cornea shortage for keratoplasties. In this study, human corneas were cryopreserved using two standard cryopreservation protocols that are employed in the Tissue Bank of the Teresa Herrera Hospital (Spain) to store corneas for tectonic keratoplasties (TK protocol) and aortic valves (AV protocol), and two vitrification protocols, VS55 and DP6. Endothelial viability and general corneal state were evaluated to determine the protocol that provides the best results. The potential corneal cryopreservation protocol was studied in detail taking into consideration some cryopreservation-related variables and the endothelial integrity and stroma arrangement of the resulting cryopreserved corneas. TK corneas showed mostly viable endothelial cells, while the others showed few (AV) or none (DP6 and VS55). The corneal structure was well maintained in TK and AV corneas. TK corneas showed endothelial acellular areas surrounded by injured cells and a normal-like stromal fiber arrangement. Cryoprotectant solutions of the TK protocol presented an increasing osmolality and a physiological pH value. Cooling temperature rate of TK protocol was of 1 °C/min to -40 °C and 3 °C/min to -120 °C, and almost all of dimethyl sulfoxide left the tissue after washing. Future studies should be done changing cryopreservation-related variables of the TK protocol to store corneas of optical grade.
Topics: Cold Temperature; Cornea; Corneal Transplantation; Cryopreservation; Dimethyl Sulfoxide; Endothelium, Corneal; Humans; Microscopy, Electron, Scanning; Spain; Tissue Banks
PubMed: 34830446
DOI: 10.3390/ijms222212564 -
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 -
Breast (Edinburgh, Scotland) Jun 2022The introduction of human epidermal growth factor receptor 2 (HER2) directed therapy has transformed the outcomes of patients with advanced breast cancer (BC). However,... (Review)
Review
IMPORTANCE
The introduction of human epidermal growth factor receptor 2 (HER2) directed therapy has transformed the outcomes of patients with advanced breast cancer (BC). However, HER2 positive breast cancer has a predilection for the central nervous system (CNS) which is associated with significant morbidity and mortality. Understanding the intracranial activity of novel HER2 directed agents is key to developing treatments as well as possible preventative strategies for HER2-positive CNS disease.
OBSERVATIONS
Using protocols and data from published phase III clinical trials for locally advanced/metastatic HER2-positive breast cancer since the licensing of single agent trastuzumab for advanced BC we review the central nervous system related aspects. This includes CNS related entry criteria, use of baseline and on study cross-sectional imaging of the CNS and protocol and non-protocol defined CNS end points and reported data.
CONCLUSIONS
and Relevance: This review found heterogeneity between studies with regard to the entry criteria, use of CNS imaging and reported end points within the pivotal phase III studies. Based on these data, a standardisation of both entry criteria and end points with regard to the CNS should be developed and applied to future studies of HER2-positive advanced BC. Such an approach would enable the generation of comparable data and allow a meaningful analysis of different treatment approaches with regard to the CNS. This in turn would allow the development of the most optimal treatment approaches for HER2 positive CNS disease and ultimately the development of preventative strategies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Central Nervous System Diseases; Clinical Trials, Phase III as Topic; Female; Humans; Receptor, ErbB-2; Trastuzumab
PubMed: 35344688
DOI: 10.1016/j.breast.2022.03.013 -
Leukemia & Lymphoma May 2017The hypomethylating agents (HMA) azacitidine and decitabine are both approved by the FDA for the treatment of myelodysplastic syndromes (MDS). Although heralded as a... (Review)
Review
The hypomethylating agents (HMA) azacitidine and decitabine are both approved by the FDA for the treatment of myelodysplastic syndromes (MDS). Although heralded as a significant advancement, HMA lead to responses in less than half of patients and for those that respond most will relapse. As such, there is a crucial need to improve frontline therapy approaches. One promising strategy involves combining azacitidine or decitabine with investigational or existing therapies with the goal of achieving synergistic activity and better patient outcomes. The purpose of this paper is to critically review the efficacy and safety of reported HMA-based combination regimens in patients with higher-risk MDS.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; DNA Methylation; Histone Deacetylase Inhibitors; Humans; Lenalidomide; Molecular Targeted Therapy; Myelodysplastic Syndromes; Protein Kinase Inhibitors; Thalidomide; Treatment Outcome
PubMed: 27654579
DOI: 10.1080/10428194.2016.1228927 -
The Lancet. Haematology Nov 2020The integration of rituximab (R) into cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) by Coiffier and colleagues was the first, and last, successful... (Review)
Review
The integration of rituximab (R) into cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) by Coiffier and colleagues was the first, and last, successful modification of this backbone regimen, which has endured now for almost 20 years. Countless attempts to redefine R-CHOP for patients with diffuse large B-cell lymphoma (DLBCL) have migrated from a focus on dose-intense and dose-dense regimens, to the use of maintenance therapies, and most recently the addition of novel agents. To date, none have changed the basic formula. Although there are many reasons for the absence of success, the incredible molecular heterogeneity of DLBCL is likely to be a major complicating factor. It is clear that as the scientific field's understanding of the genetic heterogeneity of DLBCL deepens, a precision medicine approach should be accounted for and might be one of several paths that could lead to improved outcomes. The rapid identification of poor prognostic groups within the evolving diverse molecular landscape of DLBCL will create new opportunities to produce the next generation of studies with targeted agents against specific pathological drivers. It is conceivable that targeting these driver pathways will require more than one agent, and of course, splitting the pool of patients with DLBCL into smaller groups on the basis of molecular characteristics, will reduce the number of eligible patients for clinical trial investigation. The integration of immunological agents might afford new opportunities to develop treatments agnostic to the complex molecular diversity, while adding minimal toxicity to the regimen. With each of these iterations, the hope is to ultimately shift away from a one-size-fits-all chemotherapy mentality to one predicated on an individualised approach, whether that be through the use of a targeted small molecule or a biological drug. In this Viewpoint, we explore the history of the collective efforts to improve upon R-CHOP, and underscore those lessons that might help to reshape our future plans.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Genetic Heterogeneity; Humans; Lenalidomide; Lymphoma, Large B-Cell, Diffuse; Precision Medicine; Prednisone; Prognosis; Rituximab; Vincristine
PubMed: 33091357
DOI: 10.1016/S2352-3026(20)30222-2 -
International Journal of Gynecological... Jun 2022Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to...
OBJECTIVE
Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to such agent. Although desensitization protocols can be used to re-introduce agents after the development of a hypersensitivity reaction, these protocols vary across institutions. Our study evaluated the safety and efficacy of our desensitization protocol.
METHODS
All patients who underwent desensitization to platinum, taxane, liposomal doxorubicin, or trastuzumab between November 2016 and May 2021 after a prior hypersensitivity reaction to the specific agent were included in a retrospective review. The 12-step, outpatient desensitization protocol included pretreatment with a leukotriene receptor antagonist, antihistamines, and corticosteroids, as well as extended infusion times. Successful desensitization was defined as the completion of ≥3 cycles without discontinuation of the agent due to a hypersensitivity reaction.
RESULTS
A total of 186 eligible patients were included. Median age was 59.5 years (range 26-87). 155 (83%) patients were treated with platinum. 55 (30%) patients were treated for colorectal cancer and 52 (28%) for ovarian cancer. 104 (56%) patients completed ≥3 cycles of therapy during desensitization. The median infusion time was 380 min (range 325-360 min). The median number of desensitization cycles was 3, with 694 cycles completed among all patients. A total of 79 (42%) patients had a breakthrough hypersensitivity reaction during desensitization, 4 of whom required epinephrine, and 84 (45%) patients discontinued the agent undergoing desensitization due to progression of disease.
CONCLUSIONS
Our outpatient 12-step, institutional desensitization protocol for antineoplastic therapy proved safe and efficacious, with 56% of patients successfully completing ≥3 cycles and not requiring an inpatient admission.
PubMed: 35675969
DOI: 10.1136/ijgc-2022-003466 -
Journal of Veterinary Internal Medicine Mar 2023Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak.
BACKGROUND
Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak.
HYPOTHESIS/OBJECTIVES
Investigate the efficacy of various drugs in na-IMHA.
ANIMALS
Two hundred forty-two dogs.
METHODS
Multi-institutional retrospective study (2015-2020). Immunosuppressive effectiveness was determined by time to packed cell volume (PCV) stabilization and duration of hospitalization through analysis by mixed model linear regression. Occurrence of disease relapse, death, and antithrombotic effectiveness, were analyzed using mixed model logistic regression.
RESULTS
Use of corticosteroids vs a multi-agent protocol had no effect on time to PCV stabilization (P = .55), duration of hospitalization (P = .13), or case fatality (P = .06). A higher rate of relapse (P = .04; odds ratio: 3.97; 95% confidence interval [CI]: 1.06-14.8) was detected in dogs receiving corticosteroids (11.3%) during follow-up (median: 28.5 days, range: 0-1631 days) compared to multiple agents (3.1%) during follow up (median: 47.0 days, range: 0-1992 days). When comparing drug protocols, there was no effect on time to PCV stabilization (P = .31), relapse (P = .44), or case fatality (P = .08). Duration of hospitalization was longer, by 1.8 days (95% CI: 0.39-3.28 days), for the corticosteroid with mycophenolate mofetil group (P = .01) compared to corticosteroids alone. Use of clopidogrel vs multiple agents had no effect on development of thromboses (P ≥ .36).
CONCLUSIONS AND CLINICAL IMPORTANCE
Addition of a second immunosuppressive agent did not alter immediate outcome measures but might be associated with a reduction in relapse. Use of multiple antithrombotic agents did not reduce incidence of thrombosis.
Topics: Animals; Dogs; Adrenal Cortex Hormones; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Dog Diseases; Immunosuppressive Agents; Recurrence; Retrospective Studies
PubMed: 36809664
DOI: 10.1111/jvim.16652 -
Current Oncology Reports Nov 2015Radiation therapy (RT) has been described as the most effective single agent in the treatment of lymphoma; however, contemporary lymphoma treatment rarely relies on... (Review)
Review
Radiation therapy (RT) has been described as the most effective single agent in the treatment of lymphoma; however, contemporary lymphoma treatment rarely relies on single agents. In the modern era, the selection of appropriate patients for combined modality therapy has become increasingly complex over the last decade with the transition to immunochemotherapy, the emergence of functional imaging for response evaluation, and the improvement in conformal avoidance of normal tissues when delivering RT. Recent evidence demonstrates that selected patients with DLBCL have significantly better outcomes when RT is added to immunochemotherapy; however, there are important knowledge gaps regarding the use of functional imaging to facilitate treatment selection. This article will review the current evidence regarding the optimal use of combined modality therapy for DLBCL.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Evidence-Based Practice; Humans; Immunologic Factors; Lymphoma, Large B-Cell, Diffuse; Practice Guidelines as Topic; Prednisone; Rituximab; Vincristine
PubMed: 26373412
DOI: 10.1007/s11912-015-0472-y