scholarly journals Investigational Agents for the Treatment of Resistant Yeasts and Molds

2021 ◽  
Author(s):  
Garret T. Seiler ◽  
Luis Ostrosky-Zeichner
Keyword(s):  
Yeasts And Molds ◽  
Investigational Agents

scholarly journals Protocol Deviations: A Holistic Approach from Defining to Reporting

2021 ◽  
Author(s):  
Laura Galuchie ◽  
Catherine Stewart ◽  
Frank Meloni
Keyword(s):  
Holistic Approach ◽  
Rapid Identification ◽  
Study Program ◽  
Protocol Deviation ◽  
Definition Of ◽  
Investigational Agents ◽  
Or Organization ◽  
Study Designs ◽  
Consistent Application

AbstractImproving interpretation of existing guidelines and management of protocol deviation processes could increase process efficiencies and help reduce noise to support rapid identification of important protocol deviations. Towards this end, TransCelerate identified key principles to build upon and clarify the definition of a protocol deviation and developed a holistic approach to protocol deviation management. The approaches are flexible to suit a variety of indications, study designs, and investigational agents while also supporting consistent application within a study, program or organization.

scholarly journals 556. Evaluation of Hydroxychloroquine-based Combination Therapies for the Treatment of COVID-19

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S343-S343
Author(s):  
Andrew David Berti ◽  
Pramodini Kale-Pradhan ◽  
Christopher Giuliano ◽  
Bianca Aprilliano ◽  
Christopher R Miller ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sofa Score ◽  
Laboratory Data ◽  
Organ Damage ◽  
Secondary Outcome ◽  
Mortality Data ◽  
Observational Cohort ◽  
Comorbidity Index ◽  
Significant Change ◽  
Investigational Agents

Abstract Background During the early COVID-19 pandemic a large number of investigational agents were utilized due to lack of therapeutic options. We evaluate the utility of commonly-used investigational agents combined with hydroxychloroquine (HCQ). Methods This multicenter observational cohort study included patients admitted with COVID-19 between March - May 2020 in Detroit, Michigan who received at least 2 doses of HCQ. Our primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score from presentation to day 5 of HCQ therapy with a secondary outcome of in-hospital mortality. Data collected included demographics, Charlson Comorbidity index (CCI), daily SOFA score, laboratory data and COVID-directed therapies. Multiple linear regressions were performed to control for potential confounders between different therapies and change in SOFA score. Results Three hundred thirty-five patients receiving HCQ were included. Patients were 62 ± 14.8 years of age, male (54%) and African-American (82%) with a mean CCI of 1.7 ± 1.9. In our cohort, 32% were admitted to the intensive care unit and 35% expired. Therapies received by more than 20% of patients in addition to HCQ included azithromycin (80%), zinc (76%) and vitamin D (29%). In our unadjusted analysis, a significant improvement in SOFA score was observed with zinc (0.76) while no significant change was observed with azithromycin (-0.46) or vitamin D (0.05). However, there was no significant change in SOFA score after adjusting for confounders for azithromycin, zinc and vitamin D. No difference in mortality was observed between the groups. Conclusion Overall, no benefit in end-organ damage or mortality was observed with the addition of azithromycin, zinc or vitamin D to HCQ. Further studies are needed to confirm this observation. Disclosures All Authors: No reported disclosures

426 MK-3475-U02: Phase 1/2 study of investigational agents with or without pembrolizumab versus pembrolizumab monotherapy in melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A451-A451
Author(s):  
Reinhard Dummer ◽  
Georgina V Long ◽  
Anna Pavlick ◽  
Michael Postow ◽  
Antoni Ribas ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Adaptive Design ◽  
Phase 1 ◽  
Objective Response ◽  
End Points ◽  
Investigational Agent ◽  
Link Type ◽  
Programmed Death ◽  
Investigational Agents ◽  
Study Intervention

BackgroundPembrolizumab is a standard of care for the treatment of unresectable or metastatic melanoma and an adjuvant treatment of melanoma with involvement of lymph node(s) following complete resection. However, new treatment options are needed to reduce the tumor burden before surgery and improve overall outcomes in patients with advanced melanoma.MethodsMK-3475-U02 is a phase 1/2, rolling arm, multicenter, open-label, adaptive design study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab or pembrolizumab alone for the treatment of melanoma. Patients will be enrolled in 1 of the 3 substudies. Substudy 02A will include patients with programmed death-1 (PD-1)–refractory melanoma (progressed after ≥2 doses of anti-PD-1/programmed death ligand-1 [PD-L1] therapy) randomized equally to treatment arms evaluating ≥1 investigational agent(s) with or without pembrolizumab. Enrollment is planned for up to ~100 patients per arm.Substudy 02B will include patients with unresectable stage III or stage IV melanoma not amenable to local therapy. Patients will be randomized 2:1 to combination (≥1 investigational agent(s) with or without pembrolizumab) or monotherapy (pembrolizumab alone) stratified by baseline lactate dehydrogenase status (normal/elevated) and prior adjuvant therapy with a PD-1 inhibitor (yes/no). Enrollment is planned for ~90 patients in the combination arm and ~45 in the control arm.Substudy 02C will include patients with stage IIIB/IIIC/IIID melanoma who are candidates for neoadjuvant therapy. Patients will be randomly assigned to combination (≥1 investigational agent(s) with or without pembrolizumab) or monotherapy (pembrolizumab alone). Surgical resection will be performed 6 weeks after the first dose of neoadjuvant study intervention. Enrollment is planned for ~25 patients in combination and ~15 in the pembrolizumab monotherapy arms.Treatment will continue for up to 2 years (up to 1 year neoadjuvant/adjuvant therapy for substudy 02C), until disease progression, unacceptable toxicity, or study discontinuation. The primary end points include safety (adverse events and study intervention discontinuations) for all 3 substudies; objective response rate by blinded independent central review per Response Evaluation Criteria in Solid Tumors 1.1 for substudies 02A and 02B, and pathological complete response (pCR) as assessed by central review of the pathology results for substudy 02C. Secondary end points include duration of response for substudies 02A and 02B, and recurrence-free survival, near pCR, and pathological partial response rates for substudy 02C.ResultsN/AConclusionsN/AAcknowledgementsThe authors thank the patients and their families for participating in these trials and all investigators and site personnel. Medical writing and/or editorial assistance was provided by Neha Tuli-Wildemore, MBBS, PhD, and Doyel Mitra, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationNCT04305041, NCT04305054, NCT04303169Ethics ApprovalThe study protocol and all amendments were approved by the relevant Institutional Review Board or ethics committee at each study site. All patients provided written informed consent to participate in the clinical trial.ConsentN/AReferencesN/A

scholarly journals Hemp (Cannabis sativa L.) Flour-Based Wheat Bread as Fortified Bakery Product

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1558
Author(s):  
Iulian Eugen Rusu ◽  
Romina Alina Marc (Vlaic) ◽  
Crina Carmen Mureşan ◽  
Andruţa Elena Mureşan ◽  
Vlad Mureşan ◽  
...  
Keyword(s):  
Mineral Content ◽  
Unsaturated Fatty Acids ◽  
Cannabis Sativa ◽  
New Products ◽  
Wheat Bread ◽  
Human Consumption ◽  
Nutritional Properties ◽  
Bakery Product ◽  
Nutritional Characteristics ◽  
Yeasts And Molds

Hemp flour from Dacia Secuieni and Zenit varieties was added to bread in different proportions (5%, 10%, 15% and 20%) to improve its nutritional properties. The purpose of this paper was to present the advanced nutritional characteristics of these bread samples. The selected varieties of hemp, accepted for human consumption, met the requirements for the maximum accepted level of THC in seeds. The protein content of new products increased from 8.76 to 11.48%, lipids increased from 0.59 to 5.41%, mineral content from 1.33 to 1.62%, and fiber content from 1.17 to 5.84%. Elasticity and porosity decreased from 95.51 to 80% and 78.65 to 72.24%, respectively. K, Mg, Ca, P, Mn and Fe are the main mineral substances in bread with addition of hemp flour from the Dacia Secuieni and Zenit varieties. The total amount of unsaturated fatty acids in the bread samples with hemp flour ranged from 67.93 g/100 g and 69.82 g/100 g. Eight amino acids were identified, of which three were essential (lysine, phenylalanine, histidine). Lysine, the deficient amino acid in wheat bread, increased from 0.003 to 0.101 g/100 g. Sucrose and fructose decreased with the addition of hemp flour, and glucose has not been identified. The amount of yeasts and molds decreased in the first 3 days of storage. Regarding the textural profile, the best results were obtained for the samples with 5% addition. In conclusion, bread with the addition of hemp flour has been shown to have superior nutritional properties to wheat bread.

scholarly journals Expiration Date of Ready-to-Eat Salads: Effects on Microbial Load and Biochemical Attributes

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 941
Author(s):  
Panayiota Xylia ◽  
George Botsaris ◽  
Panagiotis Skandamis ◽  
Nikolaos Tzortzakis
Keyword(s):  
Shelf Life ◽  
Foodborne Pathogens ◽  
Carbon Dioxide Production ◽  
Microbial Load ◽  
Expiration Date ◽  
Postharvest Management ◽  
Minimally Processed Vegetables ◽  
Yeasts And Molds ◽  
Staphylococcus Spp ◽  
Spoilage Microorganisms

When minimally processed vegetables reach their expiration date, expose an increased microbial load. This includes mainly spoilage microorganisms but also foodborne pathogens, thus affecting the quality and safety of highly consumed ready-to-eat salads. A total of 144 ready-to-eat salads from the Cypriot market were analyzed in an attempt to determine the effects of the expiration date on the microbial load and plant metabolic variables of the salads. Possible correlations between them were also investigated for the first time. Furthermore, the impacts of the season (winter, summer), salad producing companies and type of salad and/or their interactions with the tested parameters were investigated. Results revealed that the microbial load (mainly spoilage microorganisms, such as Pseudomonas spp., yeasts and molds) increased towards the end of the shelf life. The microbial load was differentiated among the five salad producers and/or the salad types, highlighting the importance of a common and safe sanitation-processing chain in the preparation of ready-to-eat salads. Summer was the season in which Escherichia coli counts were found to be higher for plain lettuce, while Staphylococcus spp. was increased numbers for the lettuce+endive/radicchio, lettuce+rocket and lettuce+chives type of salads. Additionally, an increased Staphylococcus spp. was observed for plain rocket salads in winter. All samples examined were found negative for Salmonella enterica and Listeria monocytogenes. Moreover, carbon dioxide production and damage indexes (hydrogen peroxide and lipid peroxidation) increased on expiration date on both winter and summer seasons, indicating plant tissue stress at the end of shelf life. These findings indicate that the expiration date and relevant shelf life of processed vegetables are important parameters to be considered when postharvest management is applied to these products, ensuring safety and quality.

scholarly journals Focused Ultrasound Strategies for Brain Tumor Therapy

2019 ◽  
Vol 19 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Adomas Bunevicius ◽  
Nathan Judson McDannold ◽  
Alexandra J Golby
Keyword(s):  
Brain Tumors ◽  
Viral Vectors ◽  
Focused Ultrasound ◽  
Tumor Therapy ◽  
Drug Distribution ◽  
Low Frequency ◽  
Tissue Level ◽  
Chemotherapeutic Agents ◽  
Promising Tool ◽  
Investigational Agents

Abstract BACKGROUND A key challenge in the medical treatment of brain tumors is the limited penetration of most chemotherapeutic agents across the blood–brain barrier (BBB) into the tumor and the infiltrative margin around the tumor. Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool to enhance the delivery of chemotherapeutic agents into brain tumors. OBJECTIVE To review the mechanism of FUS, preclinical evidence, and clinical studies that used low-frequency FUS for a BBB opening in gliomas. METHODS Literature review. RESULTS The potential of externally delivered low-intensity ultrasound for a temporally and spatially precise and predictable disruption of the BBB has been investigated for over a decade, yielding extensive preclinical literature demonstrating that FUS can disrupt the BBB in a spatially targeted and temporally reversible manner. Studies in animal models documented that FUS enhanced the delivery of numerous chemotherapeutic and investigational agents across the BBB and into brain tumors, including temozolomide, bevacizumab, 1,3-bis (2-chloroethyl)-1-nitrosourea, doxorubicin, viral vectors, and cells. Chemotherapeutic interventions combined with FUS slowed tumor progression and improved animal survival. Recent advances of MRgFUS systems allow precise, temporally and spatially controllable, and safe transcranial delivery of ultrasound energy. Initial clinical evidence in glioma patients has shown the efficacy of MRgFUS in disrupting the BBB, as demonstrated by an enhanced gadolinium penetration. CONCLUSION Thus far, a temporary disruption of the BBB followed by the administration of chemotherapy has been both feasible and safe. Further studies are needed to determine the actual drug delivery, including the drug distribution at a tissue-level scale, as well as effects on tumor growth and patient prognosis.

Improving consent forms for first-in-human trials through participant feedback.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13563-e13563
Author(s):  
Hannah Claire Sibold ◽  
Gavin Paul Campbell ◽  
John Bourgeois ◽  
Margie D. Dixon ◽  
R Donald Harvey ◽  
...  
Keyword(s):  
Patient Preferences ◽  
Clinical Trial Design ◽  
Study Drug ◽  
Clinic Visit ◽  
Consent Form ◽  
Consent Forms ◽  
Investigational Agents ◽  
Study Participants ◽  
Background Risks ◽  
Published Research

e13563 Background: Risks and benefits of investigational agents that have not been tested in humans are, at best, incompletely characterized in nonclinical investigations. Despite the growing emphasis to include patient voices in clinical trial design, no published research has explored patient preferences on how best to convey the information that the agent has not been tested in humans. This study established that First in Human (FIH) consent forms present this information in different locations and queried participants for their input on the preferable FIH consent form structure. Methods: Consent forms for FIH oncology trials open to accrual at Winship Cancer Institute in 2019-2020 were analyzed for (1) the location of the mention that the study drug has not been used in humans before (FIH information), (2) the location of animal and other nonclinical data, and (3) placement of the risks section. Patients offered enrollment in a FIH trial were eligible for this study. Participants were interviewed during a clinic visit after consent was obtained. An ethics researcher asked questions about the participant’s opinions on the wording and placement of the FIH, nonclinical, and risk information in the specific trial consent form. All interviews were audio-recorded and double coded by two independent coders. The location of FIH and nonclinical data in the consent forms was compared to the patient’s suggested location for this information. Results: Saturation of themes was reached after interviewing 17 (17/19, 89% accrual) participants who were enrolled in 9 different FIH trials. Twenty FIH consents were qualitatively analyzed. Preferred placement compared to actual consent placement is listed in the table. 82% (14/17) of participants thought that nonclinical data on risks and efficacy was important to mention. 95% (19/20) of consents listed nonclinical data and most participants thought the placement in the consent was appropriate but 18% (3/17) of participants wanted the information earlier in the consent. No consent forms that were analyzed had the risks section before the study schedule; however, 47% (8/17) of participants wanted to move the risks sections before the study schedule. Conclusions: There is considerable variation in the layout of FIH consent forms that does not align with patient preferences. Standardization of FIH consent forms to better reflect patient input is essential in order to promote understandability of these important yet sometimes misunderstood clinical trials and to ensure ethical informed consent.[Table: see text]

Evaluation of Gaseous Chlorine Dioxide as a Sanitizer for Killing Salmonella, Escherichia coli O157:H7, Listeria monocytogenes, and Yeasts and Molds on Fresh and Fresh-Cut Produce

2005 ◽  
Vol 68 (6) ◽  
pp. 1176-1187 ◽  
Author(s):  
KAYE V. SY ◽  
MELINDA B. MURRAY ◽  
M. DAVID HARRISON ◽  
LARRY R. BEUCHAT
Keyword(s):  
Escherichia Coli ◽  
Listeria Monocytogenes ◽  
Chlorine Dioxide ◽  
Foodborne Pathogens ◽  
Escherichia Coli O157 ◽  
Gaseous Chlorine Dioxide ◽  
Sensory Qualities ◽  
A Cell ◽  
Fresh Cut ◽  
Yeasts And Molds

Gaseous chlorine dioxide (ClO2) was evaluated for effectiveness in killing Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes on fresh-cut lettuce, cabbage, and carrot and Salmonella, yeasts, and molds on apples, peaches, tomatoes, and onions. Inoculum (100 μl, ca. 6.8 log CFU) containing five serotypes of Salmonella enterica, five strains of E. coli O157:H7, or five strains of L. monocytogenes was deposited on the skin and cut surfaces of fresh-cut vegetables, dried for 30 min at 22°C, held for 20 h at 4°C, and then incubated for 30 min at 22°C before treatment. The skin surfaces of apples, peaches, tomatoes, and onions were inoculated with 100 μl of a cell suspension (ca. 8.0 log CFU) containing five serotypes of Salmonella, and inoculated produce was allowed to dry for 20 to 22 h at 22°C before treatment. Treatment with ClO2 at 4.1 mg/liter significantly (α = 0.05) reduced the population of foodborne pathogens on all produce. Reductions resulting from this treatment were 3.13 to 4.42 log CFU/g for fresh-cut cabbage, 5.15 to 5.88 log CFU/g for fresh-cut carrots, 1.53 to 1.58 log CFU/g for fresh-cut lettuce, 4.21 log CFU per apple, 4.33 log CFU per tomato, 1.94 log CFU per onion, and 3.23 log CFU per peach. The highest reductions in yeast and mold populations resulting from the same treatment were 1.68 log CFU per apple and 2.65 log CFU per peach. Populations of yeasts and molds on tomatoes and onions were not significantly reduced by treatment with 4.1 mg/liter ClO2. Substantial reductions in populations of pathogens on apples, tomatoes, and onions but not peaches or fresh-cut cabbage, carrot, and lettuce were achieved by treatment with gaseous ClO2 without markedly adverse effects on sensory qualities.

Comparison of the Petrifilm™ Yeast and Mold Culture Film Method to Conventional Methods for Enumerating Yeasts and Molds in Foods

1991 ◽  
Vol 54 (6) ◽  
pp. 443-447 ◽  
Author(s):  
L. R. BEUCHAT ◽  
B. V. NAIL ◽  
R.E. BRACKETT ◽  
T. L. FOX
Keyword(s):  
Correlation Coefficients ◽  
Food Group ◽  
Black Pepper ◽  
Plate Count ◽  
Food Groups ◽  
Plate Count Agar ◽  
Plate Counts ◽  
Yeasts And Molds ◽  
Potential Food ◽  
Film Method

Petrifilm™ Yeast and Mold (YM) plates were compared to acidified potato dextrose agar (APDA) and chloramphenicol-supplemented plate count agar (CPCA) for its suitability to enumerate yeasts and molds in 13 groups of food products. These products consisted of beans (dry and frozen, green), corn meal, flour (wheat), fruit (apple), a meat/vegetable entree (chicken pot pie), a precooked meat (beef), milk (dehydrated, nonfat), nuts (pecans), pasta, potatoes (dehydrated), precooked sausage, and a spice (black pepper). Correlation coefficients of Petrifilm™ YM plates versus APDA and CPCA pour plates for recovering total yeasts and molds from a composite of the thirteen test foods were, respectively, 0.961 and 0.974. Individually, Petrifilm™ YM plate counts were equivalent or higher than APDA and CPCA for some food groups and lower for other food groups. Because food particle interference can make enumeration of yeast and mold colonies on Petrifilm™ YM plates difficult for some food groups, potential food interference will need to be evaluated for each food group tested.

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