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1.
J Adv Nurs ; 80(9): 3565-3576, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38469941

ABSTRACT

AIM: The aim of the study was to develop recommendations for creating a healthy work environment based on current literature for nurses working within the US Military Health System (MHS). However, our findings would likely benefit other nursing populations and environments as well. DESIGN: Systematic literature review. DATA SOURCES: We conducted a systematic literature search for articles published between January 2010 until January 2024 from five databases: PubMed, Joanna Briggs, Embase, CINAHL and Scopus. METHODS: Articles were screened, selected and extracted using Covidence software. Article findings were synthesized to create recommendations for the development, implementation and measurement of healthy work environments. RESULTS: Ultimately, a total of 110 articles met the criteria for inclusion in this review. The articles informed 13 recommendations for creating a healthy work environment. The recommendations included ensuring teamwork, mentorship, job satisfaction, supportive leadership, nurse recognition and adequate staffing and resources. Additionally, we identified strategies for implementing and measuring these recommendations. CONCLUSIONS: This thorough systematic review created actionable recommendations for the creation of a healthy work environment. Based on available evidence, implementation of these recommendations could improve nursing work environments. IMPACT: This study identifies methods for implementing and measuring aspects of a healthy work environment. Nurse leaders or others can implement the recommendations provided here to develop healthy work environments in their hospitals, clinics or other facilities where nurses practice. REPORTING METHOD: PRISMA 2020 guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.


Subject(s)
Working Conditions , Adult , Female , Humans , Job Satisfaction , Military Health Services , Models, Nursing , Professional Practice , United States
2.
J Nurs Adm ; 53(5): 266-270, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37098866

ABSTRACT

Professional practice models are a hallmark of professional organizations. Creating a model that can apply across contexts, however, can be a challenge. This article describes the process that a team of nurse leaders and researchers used to create a professional practice model that would serve active-duty and civilian nurses working in military treatment facilities.


Subject(s)
Military Personnel , United States , Humans , Professional Practice
3.
Nurs Outlook ; 71(3): 101949, 2023.
Article in English | MEDLINE | ID: mdl-36958117

ABSTRACT

BACKGROUND: By 2022 the Defense Health Agency became responsible for administration of all military treatment facilities (MTFs), which were previously managed by their respective military services. However, three different service-specific nursing professional practice models currently govern nursing practice in MTFs. PURPOSE: To describe the literature search, review, and synthesis of evidence which informed the JPPM and provide some of the most actionable findings. METHODS: A team of tri-service nurses developed the JPPM by conducting six rigorous systematic reviews to synthesize evidence pertaining to relevant model components. DISCUSSION: A total of 51,360 titles and abstracts were initially screened. Data were extracted from 540 included articles. The team then developed standards for five JPPM components: evidence-based practice, safety and quality, leadership development, healthy work environment, and operational readiness. CONCLUSION: The JPPM is a meaningful framework that will help create a mutual professional identity and shared vision to promote a unified nursing force in U.S. military settings.


Subject(s)
Military Personnel , Humans , Models, Nursing , Evidence-Based Practice , Professional Practice
4.
Nurs Adm Q ; 47(1): 84-93, 2023.
Article in English | MEDLINE | ID: mdl-36469376

ABSTRACT

Nursing professional practice models (PPMs) are known to have beneficial effects on nurse and patient outcomes. Determining what components should be present in a PPM, how to implement a PPM, and evaluating the outcomes associated with a PPM is less certain. Therefore, as part of a larger project to develop a nursing PPM for use within the United States Military Health System, this study aimed to conduct a systematic literature review on nursing PPMs. Specifically, the review sought to investigate components, implementation, and outcomes of PPMs in current literature. A total of 37 articles were included in the review. The literature supported the development of 12 recommendations for creating, implementing, and evaluating a nursing PPM. As health care facilities develop their own PPMs or reassess their current PPMs, findings from this review may assist hospital leadership by providing the most recent evidence on the strategic value of nursing PPMs in contemporary health care.


Subject(s)
Leadership , Models, Nursing , Humans , United States , Professional Practice , Delivery of Health Care
5.
Am J Physiol Gastrointest Liver Physiol ; 323(6): G571-G585, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36194131

ABSTRACT

Colorectal cancer (CRC) is a leading cause of cancer-related death. There is an urgent need for new methods of early CRC detection and monitoring to improve patient outcomes. Extracellular vesicles (EVs) are secreted, lipid-bilayer bound, nanoparticles that carry biological cargo throughout the body and in turn exhibit cancer-related biomarker potential. RNA binding proteins (RBPs) are posttranscriptional regulators of gene expression that may provide a link between host cell gene expression and EV phenotypes. Insulin-like growth factor 2 RNA binding protein 1 (IGF2BP1/IMP1) is an RBP that is highly expressed in CRC with higher levels of expression correlating with poor prognosis. IMP1 binds and potently regulates tumor-associated transcripts that may impact CRC EV phenotypes. Our objective was to test whether IMP1 expression levels impact EV secretion and/or cargo. We used RNA sequencing, in vitro CRC cell lines, ex vivo colonoid models, and xenograft mice to test the hypothesis that IMP1 influences EV secretion and/or cargo in human CRC. Our data demonstrate that IMP1 modulates the RNA expression of transcripts associated with extracellular vesicle pathway regulation, but it has no effect on EV secretion levels in vitro or in vivo. Rather, IMP1 appears to affect EV regulation by directly entering EVs in a transformation-dependent manner. These findings suggest that IMP1 has the ability to shape EV cargo in human CRC, which could serve as a diagnostic/prognostic circulating tumor biomarker.NEW & NOTEWORTHY This work demonstrates that the RNA binding protein IGF2BP1/IMP1 alters the transcript profile of colorectal cancer cell (CRC) mRNAs from extracellular vesicle (EV) pathways. IMP1 does not alter EV production or secretion in vitro or in vivo, but rather enters CRC cells where it may further impact EV cargo. Our work shows that IMP1 has the ability to shape EV cargo in human CRC, which could serve as a diagnostic/prognostic circulating tumor biomarker.


Subject(s)
Colorectal Neoplasms , Extracellular Vesicles , Humans , Mice , Animals , Extracellular Vesicles/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , RNA, Messenger/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/pathology
6.
Worldviews Evid Based Nurs ; 19(5): 423-425, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35044055

ABSTRACT

BACKGROUND: Anecdotal observation at a 55-bed training hospital indicated decreased patient satisfaction from patients not feeling rested during hospitalization related to staggered nighttime nursing care. AIMS: The main aim of this study is to implement a new culture of patient centeredness to enhance patient care and improve outcomes at a 34-bed Medical-Surgical Inpatient Unit (MSIU) within the training hospital. METHODS: An evidence-based practice approach was chosen to address the aim. This included the development of a PICOT (population, intervention, comparison, outcome, and time frame) question, a systematic search of the literature, a critical appraisal of the evidence, implementation of the intervention, evaluation of outcomes, and dissemination of the results. RESULTS: Twenty-three articles were critically appraised, resulting in 11 keeper articles. The body of evidence reviewed demonstrated that minimizing nighttime patient interruptions through bundled care could improve patient sleep, pain perception, and patient outcomes and reduce fatigue. Bundled care was implemented in the MSIU for 1 year. During this year, there was a significant reduction in hydrocodone administration, a notable reduction in prescription sleep aid administration, a 75% reduction in fall rates, a cost savings of $64,000, and a decrease in patient length of stay. LINKING EVIDENCE TO ACTION: Allowing patients to rest could have benefits. Rest improves outcomes, length of stay, satisfaction scores, and fall rates and reduces the need for medications. Clustering care allows patients to receive uninterrupted rest.


Subject(s)
Hydrocodone , Patient Satisfaction , Evidence-Based Practice , Hospitalization , Humans , Sleep
7.
Carcinogenesis ; 40(4): 569-579, 2019 06 10.
Article in English | MEDLINE | ID: mdl-30407516

ABSTRACT

The RNA-binding protein insulin-like growth factor 2 mRNA binding protein 1 (IMP1) is overexpressed in colorectal cancer (CRC); however, evidence for a direct role for IMP1 in CRC metastasis is lacking. IMP1 is regulated by let-7 microRNA, which binds in the 3' untranslated region (UTR) of the transcript. The availability of binding sites is in part controlled by alternative polyadenylation, which determines 3' UTR length. Expression of the short 3' UTR transcript (lacking all microRNA sites) results in higher protein levels and is correlated with increased proliferation. We used in vitro and in vivo model systems to test the hypothesis that the short 3' UTR isoform of IMP1 promotes CRC metastasis. Herein we demonstrate that 3' UTR shortening increases IMP1 protein expression and that this in turn enhances the metastatic burden to the liver, whereas expression of the long isoform (full length 3' UTR) does not. Increased tumor burden results from elevated tumor surface area driven by cell proliferation and cell survival mechanisms. These processes are independent of classical apoptosis pathways. Moreover, we demonstrate the shifts toward the short isoform are associated with metastasis in patient populations where IMP1-long expression predominates. Overall, our work demonstrates that different IMP1 expression levels result in different functional outcomes in CRC metastasis and that targeting IMP1 may reduce tumor progression in some patients.


Subject(s)
3' Untranslated Regions/genetics , Cell Proliferation , Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , RNA-Binding Proteins/genetics , Animals , Apoptosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Mice , Mice, Nude , RNA-Binding Proteins/metabolism , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
8.
Antimicrob Agents Chemother ; 60(1): 270-7, 2016 01.
Article in English | MEDLINE | ID: mdl-26503656

ABSTRACT

New regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB). Pretomanid (PMD) is a nitroimidazole in phase 3 trials that has significant bactericidal activity alone and in combination with bedaquiline (BDQ) and/or pyrazinamide (PZA). We previously showed that the novel combination of BDQ+PMD plus the oxazolidinone sutezolid (SZD) had sterilizing activity superior to that of the first-line regimen in a murine model of TB. The present experiments compared the activity of different oxazolidinones in combination with BDQ+PMD with or without PZA in the same model. The 3-drug regimen of BDQ+PMD plus linezolid (LZD) had sterilizing activity approaching that of BDQ+PMD+SZD and superior to that of the first-line regimen. The addition of PZA further enhanced activity. Reducing the duration of LZD to 1 month did not significantly affect the activity of the regimen. Halving the LZD dose or replacing LZD with RWJ-416457 modestly reduced activity over the first month but not after 2 months. AZD5847 and tedizolid also increased the bactericidal activity of BDQ+PMD, but they were less effective than the other oxazolidinones. These results provide optimism for safe, short-course oral regimens for drug-resistant TB that may also be superior to the current first-line regimen for drug-susceptible TB.


Subject(s)
Antitubercular Agents/pharmacology , Diarylquinolines/pharmacology , Nitroimidazoles/pharmacology , Oxazolidinones/pharmacology , Tuberculosis, Pulmonary/drug therapy , Animals , Bacterial Load , Disease Models, Animal , Drug Administration Schedule , Drug Combinations , Drug Resistance, Multiple, Bacterial/drug effects , Drug Synergism , Female , Linezolid/pharmacology , Lung/drug effects , Lung/microbiology , Mice , Mice, Inbred BALB C , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Organophosphates/pharmacology , Oxazoles/pharmacology , Pyrazinamide/pharmacology , Time Factors , Treatment Outcome , Tuberculosis, Pulmonary/microbiology
9.
J Head Trauma Rehabil ; 31(5): 339-45, 2016.
Article in English | MEDLINE | ID: mdl-26291633

ABSTRACT

OBJECTIVE: To compare the capacity of the Community Balance and Mobility Scale (CB&M) to identify balance and mobility deficits in Service Members (SMs) with mild traumatic brain injury and comorbid psychological health conditions (mTBI/PH) to other commonly used balance assessments. SETTING: A clinical research institute that provides a 4-week, outpatient, interdisciplinary program for active-duty SMs with mTBI/PH. DESIGN: A nonrandomized, cross-sectional design that compared multiple measures between 2 groups-active duty SMs with (n = 8) and without (n = 8) the dual diagnosis of mTBI/PH. MAIN MEASURES: Gait speed, Activities-specific Balance Confidence scale (ABC), Functional Gait Assessment (FGA), and CB&M to assess functional balance among the community-dwelling, TBI population. RESULTS: Across all measures, the mTBI/PH group performed significantly worse (P ≤ .01) with the exception of the FGA. The abilities of all objective measures to distinguish participants with mTBI/PH from healthy controls ranged from fair to excellent (area under the curve [AUC] = 0.66-0.94). However, the CB&M showed the largest group differences in effect size (d = 2.6) and had the highest discriminate ability (AUC = 0.98; sensitivity 100%; specificity 88%). CONCLUSION: The CB&M appears to have higher sensitivity and specificity than other measures of balance in SMs with mTBI/PH. A higher cut score for the CB&M is needed for this population.


Subject(s)
Brain Concussion/physiopathology , Disability Evaluation , Postural Balance , Adult , Cross-Sectional Studies , Female , Gait , Humans , Male , Military Personnel , Mobility Limitation , Pilot Projects , Walking Speed , Young Adult
10.
J Head Trauma Rehabil ; 31(1): 23-9, 2016.
Article in English | MEDLINE | ID: mdl-25699618

ABSTRACT

OBJECTIVE: To examine the use of the Neurobehavioral Symptom Inventory to measure clinical changes over time in a population of US service members undergoing treatment of mild traumatic brain injury and comorbid psychological health conditions. SETTING: A 4-week, 8-hour per day, intensive, outpatient, interdisciplinary, comprehensive treatment program at the National Intrepid Center of Excellence in Bethesda, Maryland. PARTICIPANTS: Three hundred fourteen active-duty service members being treated for combat-related comorbid mild traumatic brain injury and psychological health conditions. DESIGN: Repeated-measures, retrospective analysis of a single-group using a pretest-posttest treatment design. MAIN MEASURES: Three Neurobehavioral Symptom Inventory scoring methods: (1) a total summated score, (2) the 3-factor method, and (3) the 4-factor method (with and without orphan items). RESULTS: All 3 scoring methods yielded statistically significant within-subject changes between admission and discharge. The evaluation of effect sizes indicated that the 3 different Neurobehavioral Symptom Inventory scoring methods were comparable. CONCLUSION: Findings indicate that the different scoring methods all have potential for assessing clinical changes in symptoms for groups of patients undergoing treatment, with no clear advantage with any one method.


Subject(s)
Brain Injuries/psychology , Brain Injuries/rehabilitation , Military Personnel , Neuropsychological Tests , Adult , Ambulatory Care , Female , Humans , Male , Retrospective Studies , United States , Warfare
11.
Proc Natl Acad Sci U S A ; 110(18): 7170-5, 2013 Apr 30.
Article in English | MEDLINE | ID: mdl-23589844

ABSTRACT

College and university science departments are increasingly taking an active role in improving science education. Perhaps as a result, a new type of specialized science faculty position within science departments is emerging--referred to here as science faculty with education specialties (SFES)--where individual scientists focus their professional efforts on strengthening undergraduate science education, improving kindergarten-through-12th grade science education, and conducting discipline-based education research. Numerous assertions, assumptions, and questions about SFES exist, yet no national studies have been published. Here, we present findings from a large-scale study of US SFES, who are widespread and increasing in numbers. Contrary to many assumptions, SFES were indeed found across the nation, across science disciplines, and, most notably, across primarily undergraduate, master of science-granting, and PhD-granting institutions. Data also reveal unexpected variations among SFES by institution type. Among respondents, SFES at master of science-granting institutions were almost twice as likely to have formal training in science education compared with other SFES. In addition, SFES at PhD-granting institutions were much more likely to have obtained science education funding. Surprisingly, formal training in science education provided no advantage in obtaining science education funding. Our findings show that the SFES phenomenon is likely more complex and diverse than anticipated, with differences being more evident across institution types than across science disciplines. These findings raise questions about the origins of differences among SFES and are useful to science departments interested in hiring SFES, scientific trainees preparing for SFES careers, and agencies awarding science education funding.


Subject(s)
Faculty/statistics & numerical data , Science/education , Science/statistics & numerical data , Career Choice , Data Collection , Humans , Peer Group , Research/education , Research/statistics & numerical data , Research Support as Topic/economics , Science/economics , Teaching/statistics & numerical data , Time Factors , United States , Universities/statistics & numerical data
12.
Antimicrob Agents Chemother ; 59(1): 129-35, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25331697

ABSTRACT

New regimens based on two or more novel agents are sought in order to shorten or simplify the treatment of both drug-susceptible and drug-resistant forms of tuberculosis. PA-824 is a nitroimidazo-oxazine now in phase II trials and has shown significant early bactericidal activity alone and in combination with the newly approved agent bedaquiline or with pyrazinamide with or without moxifloxacin. While the development of PA-824 continues, a potential next-generation derivative, TBA-354, has been discovered to have in vitro potency superior to that of PA-824 and greater metabolic stability than that of the other nitroimidazole derivative in clinical development, delamanid. In the present study, we compared the activities of PA-824 and TBA-354 as monotherapies in murine models of the initial intensive and continuation phases of treatment, as well as in combination with bedaquiline plus pyrazinamide, sutezolid, and/or clofazimine. The monotherapy studies demonstrated that TBA-354 is 5 to 10 times more potent than PA-824, but selected mutants are cross-resistant to PA-824 and delamanid. The combination studies revealed that TBA-354 is 2 to 4 times more potent than PA-824 when combined with bedaquiline, and when administered at a dose equivalent to that of PA-824, TBA-354 demonstrated superior sterilizing efficacy. Perhaps most importantly, the addition of either nitroimidazole significantly improved the sterilizing activities of bedaquiline and sutezolid, with or without pyrazinamide, confirming the value of each agent in this potentially universally active short-course regimen.


Subject(s)
Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/drug effects , Nitroimidazoles/therapeutic use , Oxazines/therapeutic use , Tuberculosis/drug therapy , Animals , Clofazimine/therapeutic use , Diarylquinolines/therapeutic use , Disease Models, Animal , Drug Therapy, Combination , Female , Fluoroquinolones/therapeutic use , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Moxifloxacin , Oxazoles/therapeutic use , Pyrazinamide/therapeutic use , Random Allocation
13.
Curr Psychiatry Rep ; 17(10): 83, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26324821

ABSTRACT

Patients with post-traumatic stress disorder (PTSD) may fail to achieve adequate relief despite treatment with psychotherapy, pharmacotherapy, or complementary medicine treatments. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation procedure that can alter neuronal activity through administration of various pulse sequences and frequencies. TMS may theoretically have promise in correcting alterations observed in patients with PTSD. While the precise treatment location and pulse sequences remain undefined, current evidence suggests two promising targets, the right dorsolateral prefrontal cortex and the medial prefrontal cortex. The beneficial effects may be due to the secondary or indirect regulation of other brain structures that may be involved in the mood regulatory network. TMS may be an effective part of a comprehensive treatment program for PTSD, although significant work remains to define optimal treatment parameters and clarify how it fits within a broader traditional treatment program.


Subject(s)
Stress Disorders, Post-Traumatic/therapy , Transcranial Magnetic Stimulation/methods , Humans , Military Personnel/psychology , Prefrontal Cortex/physiology , Treatment Outcome , United States
14.
PLoS One ; 19(6): e0304426, 2024.
Article in English | MEDLINE | ID: mdl-38875222

ABSTRACT

Science education reform has been underway for almost a century with the general aim to engage students and train scientists needed to find solutions to global challenges, and also ensure a general public well disposed towards science. In an effort to aid science reform, more recently, colleges and universities have been augmenting their academic workforce by embedding education-focused science faculty into science departments. However, little research has investigated how this approach, and the identity of these faculty, may be changing over time. Here we investigate how conceptualizations of professional identities of these faculty across the United States have changed over the last two decades. We found three professional identities amongst these faculty: Science Faculty with Education Specialties (SFES), Discipline-Based Education Researchers (DBER), and faculty who identify as both SFES and DBER. Evidence indicates this is a maturing field within higher-education science departments, with more direct hiring and training pathways, but with potentially diminishing agency. Finally, data reveal resilience and perseverance despite negative biases from peers and college administrators, especially at PhD-granting institutions.


Subject(s)
Faculty , Science , United States , Faculty/psychology , Humans , Science/education , Universities , Female , Male
15.
ACG Case Rep J ; 11(9): e01494, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39286767

ABSTRACT

Ewing sarcoma (ES) is a rare malignancy that typically occurs within the skeletal system but can also develop extraskeletally. Extraskeletal ES typically presents paraspinally, in the limbs, and retroperitoneum. Rarely, it presents as a primary gastric ES. To our knowledge, there are only 13 reports of primary gastric ES, none of which originated in the cardia of the stomach. Increased identification of how extraskeletal ES, specifically primary gastric ES, presents and characterized is crucial for future treatment development and accurate prognosis. We present the case of a 36-year-old man with hematemesis, ultimately found to have primary gastric ES in the cardia.

16.
J Healthc Qual ; 46(4): 203-219, 2024.
Article in English | MEDLINE | ID: mdl-38717788

ABSTRACT

ABSTRACT: As a consistent 24-hour presence in hospitals, nurses play a pivotal role in ensuring the quality and safety (Q&S) of patient care. However, a comprehensive review of evidence-based recommendations to guide nursing interventions that enhance the Q&S of patient care is lacking. Therefore, the purpose of our systematic review was to create evidence-based recommendations for the Q&S component of a nursing professional practice model for military hospitals. To accomplish this, a triservice military nursing team used Covidence software to conduct a systematic review of the literature across five databases. Two hundred forty-nine articles met inclusion criteria. From these articles, we created 94 recommendations for practice and identified eight focus areas from the literature: (1) communication; (2) adverse events; (3) leadership; (4) patient experience; (5) quality improvement; (6) safety culture/committees; (7) staffing/workload/work environment; and (8) technology/electronic health record. These findings provide suggestions for implementing Q&S practices that could be adapted to many healthcare delivery systems.


Subject(s)
Patient Safety , Quality of Health Care , Humans , Patient Safety/standards , Quality of Health Care/standards , Quality Improvement/organization & administration , Leadership
17.
BMJ Open ; 14(1): e075501, 2024 01 12.
Article in English | MEDLINE | ID: mdl-38216190

ABSTRACT

INTRODUCTION: Rapid population ageing is a demographic trend being experienced and documented worldwide. While increased health screening and assessment may help mitigate the burden of illness in older people, issues such as misdiagnosis may affect access to interventions. This study aims to elicit the values and preferences of evidence-informed older people living in the community on early screening for common health conditions (cardiovascular disease, diabetes, dementia and frailty). The study will proceed in three Phases: (1) generating recommendations of older people through a series of Citizens' Juries; (2) obtaining feedback from a diverse range of stakeholder groups on the jury findings; and (3) co-designing a set of Knowledge Translation resources to facilitate implementation into research, policy and practice. Conditions were chosen to reflect common health conditions characterised by increasing prevalence with age, but which have been underexamined through a Citizens' Jury methodology. METHODS AND ANALYSIS: This study will be conducted in three Phases-(1) Citizens' Juries, (2) Policy Roundtables and (3) Production of Knowledge Translation resources. First, older people aged 50+ (n=80), including those from traditionally hard-to-reach and diverse groups, will be purposively recruited to four Citizen Juries. Second, representatives from a range of key stakeholder groups, including consumers and carers, health and aged care policymakers, general practitioners, practice nurses, geriatricians, allied health practitioners, pharmaceutical companies, private health insurers and community and aged care providers (n=40) will be purposively recruited for two Policy Roundtables. Finally, two researchers and six purposively recruited consumers will co-design Knowledge Translation resources. Thematic analysis will be performed on documentation and transcripts. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Torrens University Human Research Ethics Committee. Participants will give written informed consent. Findings will be disseminated through development of a policy brief and lay summary, peer-reviewed publications, conference presentations and seminars.


Subject(s)
Community Participation , Decision Making , Humans , Aged , Community Participation/methods , Policy Making , Policy
18.
Antimicrob Agents Chemother ; 56(6): 3114-20, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22470112

ABSTRACT

Novel oral regimens composed of new drugs with potent activity against Mycobacterium tuberculosis and no cross-resistance with existing agents are needed to shorten and simplify treatment for both drug-susceptible and drug-resistant tuberculosis. As part of a continuing effort to evaluate novel drug combinations for treatment-shortening potential in a murine model, we performed two long-term, relapse-based experiments. In the first experiment, several 3- and 4-drug combinations containing new agents currently in phase 2/3 trials (TMC207 [bedaquiline], PA-824 and PNU-100480 [sutezolid], and/or clofazimine) proved superior to the first-line regimen of rifampin, pyrazinamide, and isoniazid. TMC207 plus PNU-100480 was the most effective drug pair. In the second experiment, in which 3- and 4-drug combinations composed of TMC207 and pyrazinamide plus rifapentine, clofazimine, PNU-100480, or both rifapentine and clofazimine were evaluated, the rank order of drugs improving the sterilizing activity of TMC207 and pyrazinamide was as follows: rifapentine plus clofazimine ≥ clofazimine ≥ rifapentine > PNU-100480. The results revealed potential new building blocks for universally active short-course regimens for drug-resistant tuberculosis. The inclusion of pyrazinamide against susceptible isolates may shorten the duration of treatment further.


Subject(s)
Antitubercular Agents/administration & dosage , Antitubercular Agents/therapeutic use , Tuberculosis/drug therapy , Animals , Drug Therapy, Combination , Female , Isoniazid/administration & dosage , Isoniazid/therapeutic use , Mice , Mice, Inbred BALB C , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/pathogenicity , Nitroimidazoles/administration & dosage , Nitroimidazoles/therapeutic use , Oxazolidinones/administration & dosage , Oxazolidinones/therapeutic use , Pyrazinamide/administration & dosage , Pyrazinamide/therapeutic use , Rifampin/administration & dosage , Rifampin/analogs & derivatives , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy
19.
Am J Respir Crit Care Med ; 184(6): 732-7, 2011 Sep 15.
Article in English | MEDLINE | ID: mdl-21659613

ABSTRACT

RATIONALE: Multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) is an emerging global health threat. Proper management of close contacts of infectious patients is increasingly important. However, no evidence-based recommendations for treating latent TB infection (LTBI) after MDR/XDR-TB exposure (DR-LTBI) exist. An ultrashort regimen for LTBI caused by drug-susceptible strains (DS-LTBI) is also desirable. TMC207 has bactericidal and sterilizing activity in animal models of TB and improves the activity of current MDR-TB therapy in patients. OBJECTIVES: The objective of this study was to determine whether TMC207 might enable short-course treatment of DR-LTBI and ultrashort treatment of DS-LTBI. METHODS: Using an established experimental model of LTBI chemotherapy in which mice are aerosol-immunized with a recombinant bacillus Calmette-Guérin vaccine before low-dose aerosol infection with Mycobacterium tuberculosis, the efficacy of TMC207 alone and in combination with rifapentine was compared with currently recommended control regimens as well as once-weekly rifapentine + isoniazid and daily rifapentine ± isoniazid. MEASUREMENTS: Outcomes included monthly lung colony-forming unit counts and relapse rates. MAIN RESULTS: Lung colony-forming unit counts were stable at about 3.75 log(10) for up to 7.5 months postinfection in untreated mice. Rifamycin-containing regimens were superior to isoniazid monotherapy. TMC207 exhibited sterilizing activity at least as strong as that of rifampin alone and similar to that of rifampin + isoniazid, but daily rifapentine +/- isoniazid was superior to TMC207. Addition of TMC207 to rifapentine did not improve the sterilizing activity of rifapentine in this model. CONCLUSIONS: TMC207 has substantial sterilizing activity and may enable treatment of DR-LTBI in 3-4 months.


Subject(s)
Antibiotics, Antitubercular/administration & dosage , Antitubercular Agents/administration & dosage , Latent Tuberculosis/drug therapy , Quinolines/administration & dosage , Rifampin/analogs & derivatives , Animals , Diarylquinolines , Disease Models, Animal , Drug Administration Schedule , Drug Therapy, Combination/methods , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/microbiology , Female , Latent Tuberculosis/microbiology , Lung/drug effects , Lung/microbiology , Mice , Mice, Inbred BALB C , Mycobacterium tuberculosis/drug effects , Rifampin/administration & dosage , Stem Cells/drug effects , Treatment Outcome
20.
Antimicrob Agents Chemother ; 55(4): 1781-3, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21282421

ABSTRACT

DC-159a is a new fluoroquinolone with more potent in vitro activity than available fluoroquinolones against both drug-susceptible and fluoroquinolone-resistant Mycobacterium tuberculosis. Here, we report that DC-159a displays pharmacokinetics similar to those of moxifloxacin yet is more active than moxifloxacin during both the initial and continuation phases of treatment in a murine model. These results warrant further preclinical evaluation of DC-159a in selected drug combinations against drug-susceptible and fluoroquinolone-resistant tuberculosis.


Subject(s)
Aminopyridines/therapeutic use , Antitubercular Agents/therapeutic use , Fluoroquinolones/therapeutic use , Tuberculosis/drug therapy , Aminopyridines/blood , Aminopyridines/pharmacokinetics , Animals , Antitubercular Agents/blood , Antitubercular Agents/pharmacokinetics , Female , Fluoroquinolones/blood , Fluoroquinolones/pharmacokinetics , Mice , Mice, Inbred BALB C
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