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1.
J Med Radiat Sci ; 69(3): 318-326, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35289107

ABSTRACT

INTRODUCTION: Adaptive communication is an essential requirement to deliver quality patient-centred care. Determining patients' informational needs and acting on the needs are skills radiation therapists (RTs) employ daily with patients. Learning health literacy (HL) strategies to assist with the informational delivery provides RTs with options to improve patients' understanding of vital radiotherapy treatment information or tasks. This research investigates the lived experiences of RTs from the Illawarra and Shoalhaven Cancer Care Centres in Australia using HL strategies during patient interactions after undertaking HL training workshops. METHODS: An interpretative phenomenological analysis (IPA) approach was used. Audio-recorded semi-structured interviews were conducted with six RTs. Two reviewers analysed each interview script separately before discussing and constructing substantive and sub-themes. RESULTS: Four substantive themes were constructed: RT personal attitudes and responses to HL, HL strategies used by RTs, patient associated HL needs and barriers when addressing patient HL needs. RTs were either person- or process-focussed during patient interactions. It was identified that information is provided to patients according to how RTs themselves like to learn new information. CONCLUSION: This research has allowed an opportunity to inquire into the lived experiences of RTs implementing HL strategies when providing information to patients. While RTs may be person or process-focussed, the patient's needs are always prioritised when providing information, which ultimately results in patient understanding and increased engagement.


Subject(s)
Health Literacy , Radiation Oncology , Australia , Communication , Health Literacy/methods , Humans , Patient-Centered Care , Qualitative Research
2.
Antimicrob Agents Chemother ; 66(1): e0139721, 2022 01 18.
Article in English | MEDLINE | ID: mdl-34633850

ABSTRACT

KBP-7072 is a novel broad-spectrum tetracycline (aminomethylcycline) antibacterial in clinical development (oral and intravenous formulations) for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and complicated intra-abdominal infections. KBP-7072 is active against many of the World Health Organization priority pathogens. In this study, KBP-7072 and tetracycline class comparators were susceptibility tested against 1,057 geographically diverse surveillance isolates from 2019 according to Clinical and Laboratory Standards Institute (CLSI) guidelines. KBP-7072 demonstrated potent in vitro activity against Gram-positive and Gram-negative bacterial pathogens. KBP-7072 was active against Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/liter), methicillin-resistant S. aureus (MIC50/90, 0.06/0.12 mg/liter), S. lugdunensis (MIC50/90, 0.03/0.03 mg/liter), and other coagulase-negative staphylococci (MIC50/90, 0.06/0.25 mg/liter). KBP-7072 was active against Enterococcus faecalis (MIC50/90, 0.03/0.06 mg/liter) and vancomycin-susceptible and -nonsusceptible E. faecium (MIC50/90, 0.03/0.03 mg/liter); Streptococcus pneumoniae (MIC50/90, ≤0.015/0.03 mg/liter), including penicillin- and tetracycline-resistant strains; S. agalactiae (MIC50/90, 0.03/0.06 mg/liter), including macrolide-resistant strains; S. pyogenes (MIC50/90, 0.03/0.03 mg/liter); and viridans group streptococci, including S. anginosus group (MIC50/90, ≤0.015/0.03 mg/liter) isolates. KBP-7072 inhibited 90.2% (MIC50/90, 0.25/2 mg/liter) of all Enterobacterales isolates, including expanded-spectrum ß-lactamase-phenotype strains at ≤2 mg/liter. KBP-7072 demonstrated potent activity against Acinetobacter baumannii-calcoaceticus species complex and Stenotrophomonas maltophilia isolates (MIC50/90 values, 0.5/1 mg/liter), Haemophilus influenzae (MIC50/90, 0.12/0.25 mg/liter; 100.0% inhibited at ≤0.25 mg/liter), and Moraxella catarrhalis (MIC50/90, 0.06/0.06 mg/liter). Based on MIC90 values, KBP-7072 in vitro activity was generally superior to that the other tetracycline class comparators tested. The potent activity of KBP-7072, including resistant organism groups, merits further clinical investigation in infections where these organisms are likely to occur.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria , Gram-Positive Bacteria , Microbial Sensitivity Tests , Tetracyclines/pharmacology
3.
Am J Infect Control ; 50(7): 792-798, 2022 07.
Article in English | MEDLINE | ID: mdl-34742749

ABSTRACT

BACKGROUND: Healthcare-associated infections (HAIs) are a persistent clinical challenge caused primarily by bacteria on the skin. Proper utilization of optimized antiseptic skin preparation solutions helps reduce the prevalence and impact of HAIs by decreasing patient skin microorganisms preoperatively. The purpose of this study was to evaluate the efficacy of 2 antimicrobial solutions containing iodine and isopropyl alcohol (IPA): Povidone iodine (PVP-I) with IPA (ie, PVP-I+IPA, PurPrep) and Iodine Povacrylex+IPA (DuraPrep). METHODS: The antimicrobial activity of the test solutions was evaluated in vitro by determinations of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against 1105 diverse microbial isolates and a time-kill assay to evaluate efficacy against 120 strains of Gram-positive and Gram-negative bacteria and yeasts. Peel tests were performed between skin samples treated with test solutions and representative drape/dressing materials to determine effects of test solutions on the biomechanical adhesion properties. Finally, an Institutional Review Board (IRB)-approved, randomized, controlled, single-center, partially blinded in vivo study was performed to assess the immediate and persistent antimicrobial activity of the test solutions on the abdomen and groin. RESULTS: Both PVP-I+IPA and Iodine Povacrylex+IPA solutions demonstrated broad-spectrum antimicrobial activity with MIC and MBC at less than 1% of the full-strength concentration of each product against a wide variety of microorganisms. In the time-kill tests, both solutions were able to successfully reduce all microbial populations by 99.99% (ie, 4 log10) at the contact times of 30 seconds, 2 minutes and 10 minutes. The 2 solutions showed relatively similar adhesion results when tested with 3 representative operating room materials. Both PVP-I+IPA and Iodine Povacrylex+IPA met the expected Food and Drug Administration (FDA) efficacy requirements at 10 minutes and 6 hours post-treatment for both anatomic sites (ie, groin, and abdomen) in the clinical study, with no safety issues or adverse events. CONCLUSIONS: Analysis of the in vitro antimicrobial activity, biomechanical adhesive strength, and in vivo efficacy of PVP-I+IPA demonstrated similar results compared to Iodine Povacrylex+IPA. Both products were efficacious at reducing or eliminating a wide range of clinically-relevant microorganisms in lab-based and clinical settings, supporting their use as antiseptic skin preparation solutions to reduce bacteria on the skin that can cause infection.


Subject(s)
Anti-Infective Agents, Local , Iodine , 2-Propanol/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents, Local/pharmacology , Anti-Infective Agents, Local/therapeutic use , Bacteria , Chlorhexidine/pharmacology , Gram-Negative Bacteria , Gram-Positive Bacteria , Humans , Iodine/pharmacology , Povidone-Iodine/pharmacology , Skin/microbiology , Surgical Wound Infection/epidemiology
4.
Nat Biotechnol ; 28(6): 585-93, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20495549

ABSTRACT

The low rate of approval of novel anti-cancer agents underscores the need for better preclinical models of therapeutic response as neither xenografts nor early-generation genetically engineered mouse models (GEMMs) reliably predict human clinical outcomes. Whereas recent, sporadic GEMMs emulate many aspects of their human disease counterpart more closely, their ability to predict clinical therapeutic responses has never been tested systematically. We evaluated the utility of two state-of-the-art, mutant Kras-driven GEMMs--one of non-small-cell lung carcinoma and another of pancreatic adenocarcinoma--by assessing responses to existing standard-of-care chemotherapeutics, and subsequently in combination with EGFR and VEGF inhibitors. Standard clinical endpoints were modeled to evaluate efficacy, including overall survival and progression-free survival using noninvasive imaging modalities. Comparisons with corresponding clinical trials indicate that these GEMMs model human responses well, and lay the foundation for the use of validated GEMMs in predicting outcome and interrogating mechanisms of therapeutic response and resistance.


Subject(s)
Disease Models, Animal , Genetic Engineering , Mutation/genetics , Neoplasms/genetics , Neoplasms/therapy , Proto-Oncogene Proteins p21(ras)/genetics , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/pathology , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Erlotinib Hydrochloride , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice , Quinazolines/therapeutic use , Survival Analysis , Vascular Endothelial Growth Factor A/immunology , Gemcitabine
5.
Proc Natl Acad Sci U S A ; 105(7): 2640-5, 2008 Feb 19.
Article in English | MEDLINE | ID: mdl-18268320

ABSTRACT

The secreted Bv8 protein has been recently characterized as a regulator of myeloid cell mobilization and a neutrophil-derived mediator of tumor angiogenesis in several xenografts, but its role in tumor progression in an endogenous setting was unknown. The rat insulin promoter (RIP)-T-antigen (Tag) is a well characterized transgenic mouse model of multistage pancreatic beta-cell tumorigenesis. Also, the role of neutrophils in RIP-Tag angiogenic switching, as assessed by systemic ablation using anti-Gr1 antibodies at different stages of tumor progression, has been recently described. Here, we show that early treatment of RIP-Tag mice with anti-Bv8 antibodies resulted in a significant reduction in the number of angiogenic islets relative to control antibody-treated mice, implicating Bv8 in the angiogenic switch during neoplasia. Histological analysis showed a significant reduction in vascular surface areas in hyperplastic and angiogenic lesions in pancreatic islets from anti-Bv8-treated mice. Anti-Bv8 treatment also inhibited the mobilization and homing of CD11b+Gr1+ cells to the peripheral blood and the emerging neoplastic lesions. However, anti-Bv8 treatment had no effect on tumor vascularization or burden when initiated at later stages of tumor progression. The stage-dependent efficacy of anti-Bv8 treatment appears remarkably similar to that reported after neutrophil ablation, suggesting that Bv8 is an important mediator of neutrophil-dependent angiogenesis in this transgenic model. In summary, our studies verify a role for Bv8 in the mobilization and recruitment of myeloid cells and in the induction of tumor angiogenesis in the early stages of neoplastic progression.


Subject(s)
Gastrointestinal Hormones/metabolism , Neoplasms/blood supply , Neoplasms/metabolism , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Neuropeptides/metabolism , Neutrophils/metabolism , Animals , Bone Marrow/metabolism , CD11b Antigen/metabolism , Disease Progression , Gastrointestinal Hormones/genetics , Gastrointestinal Hormones/immunology , Gene Expression Regulation, Neoplastic , Insulin/genetics , Mice , Mice, Transgenic , Neoplasm Staging , Neoplasms/genetics , Neoplasms/pathology , Neovascularization, Pathologic/genetics , Neuropeptides/genetics , Neuropeptides/immunology , Neutrophil Infiltration , Pancreas/metabolism , Promoter Regions, Genetic/genetics , Rats
6.
Cancer Res ; 62(13): 3736-42, 2002 Jul 01.
Article in English | MEDLINE | ID: mdl-12097283

ABSTRACT

The leukocyte activation marker CD30 is highly expressed on the Reed Sternberg cells of Hodgkin's disease (HD). On normal tissues, CD30 has a restricted expression profile limited to activated T cells, activated B cells, and activated natural killer cells. This expression profile makes CD30 an ideal target for monoclonal antibody (mAb)-based therapies of Hodgkin's disease. CD30 mAbs have been shown to be effective in in vitro and in vivo models of hematologic malignancies such as anaplastic large cell lymphoma, yet these mAb have not been efficacious in HD models. We have found that a mAb against CD30, AC10, was able to inhibit the growth of HD cell lines in vitro. To generate a more clinically relevant molecule, the variable regions from AC10 were cloned into an expression construct containing the human gamma1 heavy chain and kappa light chain constant regions. The resulting chimeric antibody, designated SGN-30, retained the binding and in vitro growth-inhibitory activities of the parental antibody. Treatment of HD cell lines with SGN-30 in vitro resulted in growth arrest in the G(1) phase of the cell cycle and DNA fragmentation consistent with apoptosis in the HD line L540cy. Severe combined immunodeficient mouse xenograft models of disseminated HD treated with SGN-30 produced significant increases in survival. Similarly, xenograft models of localized HD demonstrated dose-dependent reduction in tumor mass in response to SGN-30 therapy. SGN-30 is being developed for the treatment of patients who have HD that is refractory to initial treatment or who have relapsed and have limited therapeutic options.


Subject(s)
Antibodies, Monoclonal/pharmacology , DNA Fragmentation , Hodgkin Disease/therapy , Ki-1 Antigen/immunology , Animals , Antibodies, Monoclonal/biosynthesis , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/immunology , CHO Cells , Cell Cycle/drug effects , Cell Division/drug effects , Cricetinae , Hodgkin Disease/genetics , Hodgkin Disease/immunology , Hodgkin Disease/pathology , Humans , Hybridomas , Mice , Mice, SCID , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
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