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1.
Aust Occup Ther J ; 69(5): 599-624, 2022 10.
Article in English | MEDLINE | ID: mdl-35674225

ABSTRACT

INTRODUCTION: Low implementation rates of occupational therapy home assessment recommendations have previously been reported. The objective was to identify and describe the barriers and facilitating factors that influence implementation of home assessment recommendations. METHODS: A mixed methods systematic review consisting of studies involving adults living in the community who received an occupational therapy home assessment was conducted. Seven databases were last searched in August 2021. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools (SUMARI) dependent on study design. Data synthesis followed the convergent integrated approach. Findings were mapped to the theoretical Capability Opportunity Motivation Behaviour (COM-B) model of health behaviour change. RESULTS: From 5,540 citations, 22 articles met the criteria for the systematic review. Implementation of occupational therapy home assessment recommendations ranged between 55% and 90%. Six synthesised findings were identified. Capability barriers included a patient's cognitive and physical ability. Motivation barriers included a perceived lack of need and stigma; patient reported decreased involvement and lack of choice. Opportunity barriers included limited family or carer involvement, carer stress, level of service provision available, including funding, therapy dosage and timing and environmental restrictions. Overall facilitators included patient-centred care, including choice and understanding need, individualised tailored recommendations, involvement of families and carers, provision of written record and strategies to support implementation. Results were limited by methodological weaknesses in identified studies and heterogeneity in the definition and measurement of implementation impacting on comparison. Specific intervention components were often poorly described. CONCLUSION: The theoretical model elucidates priority factors to address for promoting implementation of home assessment recommendations. Future high-quality research clearly defining intervention components is required to support short- and long-term implementation of recommendations in the home environment. Behaviour change techniques could be utilised to support home assessment practices in future research.


Subject(s)
Occupational Therapy , Adult , Caregivers , Humans , Motivation
2.
Cells ; 11(8)2022 04 08.
Article in English | MEDLINE | ID: mdl-35455947

ABSTRACT

Ewing sarcoma (ES) is a rare aggressive cancer of bone and soft tissue that is mainly characterized by a reciprocal chromosomal translocation. As a result, about 90% of cases express the EWS-FLI1 fusion protein that has been shown to function as an aberrant transcription factor driving sarcomagenesis. ES is the second most common malignant bone tumor in children and young adults. Current treatment modalities include dose-intensified chemo- and radiotherapy, as well as surgery. Despite these strategies, patients who present with metastasis or relapse still have dismal prognosis, warranting a better understanding of treatment resistant-disease biology in order to generate better prognostic and therapeutic tools. Since the genomes of ES tumors are relatively quiet and stable, exploring the contributions of epigenetic mechanisms in the initiation and progression of the disease becomes inevitable. The search for novel biomarkers and potential therapeutic targets of cancer metastasis and chemotherapeutic drug resistance is increasingly focusing on long non-coding RNAs (lncRNAs). Recent advances in genome analysis by high throughput sequencing have immensely expanded and advanced our knowledge of lncRNAs. They are non-protein coding RNA species with multiple biological functions that have been shown to be dysregulated in many diseases and are emerging as crucial players in cancer development. Understanding the various roles of lncRNAs in tumorigenesis and metastasis would determine eclectic avenues to establish therapeutic and diagnostic targets. In ES, some lncRNAs have been implicated in cell proliferation, migration and invasion, features that make them suitable as relevant biomarkers and therapeutic targets. In this review, we comprehensively discuss known lncRNAs implicated in ES that could serve as potential biomarkers and therapeutic targets of the disease. Though some current reviews have discussed non-coding RNAs in ES, to our knowledge, this is the first review focusing exclusively on ES-associated lncRNAs.


Subject(s)
Bone Neoplasms , RNA, Long Noncoding , Sarcoma, Ewing , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Child , Epigenesis, Genetic , Humans , Neoplasm Recurrence, Local/genetics , RNA, Long Noncoding/genetics , Sarcoma, Ewing/genetics , Sarcoma, Ewing/pathology , Young Adult
3.
Cells ; 10(11)2021 10 29.
Article in English | MEDLINE | ID: mdl-34831167

ABSTRACT

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, well-tolerated and more successful treatments for a significant improvement of patients' quality of life and disease outcome. In this review, we provide comparative mechanistic insights into the bone metastatic process of various solid tumors, including pediatric cancers. We also highlight current and innovative approaches to biologically targeted therapy and immunotherapy. In particular, we discuss the role of the bone marrow microenvironment in the attraction, homing, dormancy and outgrowth of metastatic tumor cells and the ensuing therapeutic implications. Multiple signaling pathways have been described to contribute to metastatic spread to the bone of specific cancer entities, with most knowledge derived from the study of breast and prostate cancer. However, it is likely that similar mechanisms are involved in different types of cancer, including multiple myeloma, primary bone sarcomas and neuroblastoma. The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.


Subject(s)
Bone Neoplasms/diagnosis , Bone Neoplasms/secondary , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Bone Neoplasms/therapy , Epithelial-Mesenchymal Transition , Humans , Immunotherapy , Models, Biological , Tumor Microenvironment
4.
Oncogenesis ; 10(1): 2, 2021 Jan 08.
Article in English | MEDLINE | ID: mdl-33419969

ABSTRACT

Ewing sarcoma (EwS) is a highly metastatic bone cancer characterized by the ETS fusion oncoprotein EWS-FLI1. EwS cells are phenotypically highly plastic and switch between functionally distinct cell states dependent on EWS-FLI1 fluctuations. Whereas EWS-FLI1high cells proliferate, EWS-FLI1low cells are migratory and invasive. Recently, we reported activation of MRTFB and TEAD, effectors of RhoA and Hippo signalling, upon low EWS-FLI1, orchestrating key steps of the EwS migratory gene expression program. TEAD and its co-activators YAP and TAZ are commonly overexpressed in cancer, providing attractive therapeutic targets. We find TAZ levels to increase in the migratory EWS-FLI1low state and to associate with adverse prognosis in EwS patients. We tested the effects of the potent YAP/TAZ/TEAD complex inhibitor verteporfin on EwS cell migration in vitro and on metastasis in vivo. Verteporfin suppressed expression of EWS-FLI1 regulated cytoskeletal genes involved in actin signalling to the extracellular matrix, effectively blocked F-actin and focal-adhesion assembly and inhibited EwS cell migration at submicromolar concentrations. In a mouse EwS xenograft model, verteporfin treatment reduced relapses at the surgical site and delayed lung metastasis. These data suggest that YAP/TAZ pathway inhibition may prevent EwS cell dissemination and metastasis, justifying further preclinical development of YAP/TAZ inhibitors for EwS treatment.

5.
JBI Evid Synth ; 19(2): 440-446, 2021 02.
Article in English | MEDLINE | ID: mdl-33165179

ABSTRACT

OBJECTIVE: To identify and describe the barriers and facilitators that influence adherence to recommendations provided as part of an occupational therapy home assessment. INTRODUCTION: Home assessments, including environmental interventions, are commonly used by occupational therapists. Home assessment recommendations aim to support a patient's independence in their occupational roles and improve safety in the home. Research evaluating home assessments and adherence to recommended strategies is limited. However, low adherence has been associated with poorer outcomes including falls, deconditioning, and decreased function. This research aims to synthesize factors that influence adherence to home assessment recommendations. INCLUSION CRITERIA: This review will consider all qualitative and quantitative studies that report on adherence to recommendations provided during occupational therapy home assessments. Studies will include adults (>18) and/or their caregivers, who live in the community and receive an occupational therapy home assessment. METHODS: A mixed methods systematic review will be undertaken. Eight databases will be searched for studies published in English reporting on adherence following home assessments completed by occupational therapists published after January 2000. Study quality will be assessed using standardized JBI critical appraisal tools dependent on study design. Data extraction will be performed using a standardized tool, followed by data transformation. Data synthesis will follow the convergent integrated approach. All findings will be tabulated to explore factors that influence adherence. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020159233.


Subject(s)
Occupational Therapy , Accidental Falls , Adult , Caregivers , Humans , Occupational Therapists , Review Literature as Topic , Systematic Reviews as Topic
7.
Case Rep Nephrol ; 2019: 8720837, 2019.
Article in English | MEDLINE | ID: mdl-31093390

ABSTRACT

A 53-year-old woman is admitted with a serum creatinine of 16 mg/dl. Seven months earlier, she was diagnosed with heart failure and started on several medications, including Hydralazine. Laboratory studies revealed the presence of dual Anti-Neutrophil Cytoplasmic Antibodies (anti-MPO and anti-PR3), anti-nuclear and anti-histone antibodies. The clinical diagnosis was Drug-Induced ANCA Vasculitis (DIAV). Kidney histology, however, did not reveal crescents, but showed characteristic features of Alport's syndrome.

8.
Respir Care ; 64(4): 361-371, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30723169

ABSTRACT

BACKGROUND: Different brands of volume-targeted modes may vary the location of tidal volume (VT) monitoring and whether peak inspiratory pressure is adjusted based on inspiratory, expiratory, or leak-compensated VT. These variables may result in different levels of support provided to patients, especially when an endotracheal tube (ETT) leak is present. We hypothesized that there would be no differences in gas exchange, triggering, or work of breathing between volume-targeted modes of 3 different brands of equipment in a surfactant-deficient, spontaneously breathing animal model with and without an ETT leak. METHODS: Twelve rabbits (mean ± SD 1.61 ± 0.20 kg) were sedated, anesthetized, intubated, lavaged with 0.9% saline solution, and randomized in a crossover design so that each animal was supported by 3 different volume-targeted modes at identical settings with and without an ETT leak. After 30 min, arterial blood gas, VT, and esophageal and airway pressure were recorded for each condition, and pressure-rate product and percentage of successfully triggered breaths were calculated. RESULTS: Gas exchange and the pressure-rate product were not different between the ventilators in the absence of an ETT leak. When an ETT leak was introduced, volume-guarantee modes allowed a higher percentage of triggered breaths and peak inspiratory pressure, which resulted in higher minute ventilation, pH, and lower PaCO2 than the pressure-regulated volume control mode (P < .05). CONCLUSIONS: When a moderate ETT leak was present, volume-targeted modes that used proximal VT monitoring and triggering with adaptive leak compensation capabilities appeared more effective in providing ventilation support than did a ventilator that used measurements obtained from the back at the ventilator and does not have leak compensation.


Subject(s)
Intubation, Intratracheal , Pulmonary Gas Exchange/physiology , Respiration, Artificial , Tidal Volume , Ventilators, Mechanical , Animals , Animals, Newborn/physiology , Blood Gas Analysis/methods , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/instrumentation , Intubation, Intratracheal/methods , Materials Testing , Models, Animal , Monitoring, Physiologic/methods , Pulmonary Surfactants/metabolism , Rabbits , Respiration, Artificial/instrumentation , Respiration, Artificial/methods , Respiratory Function Tests/methods , Respiratory Mechanics/physiology , Ventilators, Mechanical/classification , Ventilators, Mechanical/standards
9.
Oncotarget ; 9(57): 31018-31031, 2018 Jul 24.
Article in English | MEDLINE | ID: mdl-30123424

ABSTRACT

Ewing sarcoma (EwS) is an aggressive pediatric bone cancer in need of more effective therapies than currently available. Most research into novel targeted therapeutic approaches is focused on the fusion oncogene EWSR1-FLI1, which is the genetic hallmark of this disease. In this study, a broad range of 3,325 experimental compounds, among them FDA approved drugs and natural products, were screened for their effect on EwS cell viability depending on EWS-FLI1 expression. In a network-based approach we integrated the results from drug perturbation screens and RNA sequencing, comparing EWS-FLI1-high (normal expression) with EWS-FLI1-low (knockdown) conditions, revealing novel interactions between compounds and EWS-FLI1 associated biological processes. The top candidate list of druggable EWS-FLI1 targets included genes involved in translation, histone modification, microtubule structure, topoisomerase activity as well as apoptosis regulation. We confirmed our in silico results using viability and apoptosis assays, underlining the applicability of our integrative and systemic approach. We identified differential sensitivities of Ewing sarcoma cells to BCL-2 family inhibitors dependent on the EWS-FLI1 regulome including altered MCL-1 expression and subcellular localization. This study facilitates the selection of effective targeted approaches for future combinatorial therapies of patients suffering from Ewing sarcoma.

11.
Can J Respir Ther ; 54(1)2018.
Article in English | MEDLINE | ID: mdl-29636639

ABSTRACT

INTRODUCTION: This study was designed to evaluate short-term physiologic outcomes of transitioning neonates with bronchopulmonary dysplasia (BPD) from intensive care unit (ICU) ventilators to both the Trilogy 202 (Philips Healthcare, Andover, MA) and LTV 1200 (CareFusion, Yorba Linda, CA) subacute ventilators. METHODS: Six infants with BPD requiring tracheostomies for support with a neonatal-specific ICU ventilator underwent placement of esophageal balloon catheters, airway pressure transducers, flow sensors, oxygen saturation (SpO2), and end tidal carbon dioxide (PETCO2) monitors. Noninvasive gas exchange, airflow, and airway and esophageal pressures (PES) were recorded following 20 min on the ICU ventilator. The infants were placed on the Trilogy 202 and LTV 1200 ventilators in random order at identical settings as the ICU ventilator. We measured noninvasive gas exchange, pressure-rate product (respiratory rate × ΔPES), ventilator response times, and the percentage of spontaneous breaths that triggered the ventilator at 20 min in each subject while being supported with each of the different subacute ventilators. RESULTS: The mean (SD) weight of the six infants was 4.983 (0.56) kg. There were no differences in heart rate (p = 0.51) or SpO2 (p = 0.97) but lower PETCO2, ΔPES, respiratory rate, pressure rate-product, response times, and greater percentage of subject initiated breaths that triggered the ventilator (p < 0.05) was observed with the Trilogy 202 than the LTV 1200. All six infants transitioned successfully from the ICU ventilator to the Trilogy 202 ventilator. CONCLUSION: In this small group of infants with BPD, the Trilogy 202 ventilator performed better than the LTV 1200. The improved subject efforts, per cent subject triggering, and response times observed with the Trilogy are likely related to differences in triggering algorithms, location of triggering mechanisms, and gas delivery system performance within the ventilators. These pilot data may be useful for informing future clinical study design and understanding differences in the level of support provided by different subacute ventilators in infants with BPD.

12.
Pediatr Crit Care Med ; 18(6): e253-e260, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28441181

ABSTRACT

OBJECTIVES: To determine the feasibility of delivering inhaled treprostinil during mechanical ventilation and spontaneous unassisted ventilation using the Tyvaso Inhalation System and the vibrating mesh nebulizer. We sought to compare differences in fine particle fraction, and absolute inhaled treprostinil mass delivered to neonatal, pediatric, and adult models affixed with a face mask, conventional, and high-frequency ventilation between Tyvaso Inhalation System and with different nebulizer locations between Tyvaso Inhalation System and vibrating mesh nebulizer. DESIGN: Fine particle fraction was first determined via impaction with both the Tyvaso Inhalation System and vibrating mesh nebulizer. Next, a test lung configured with neonatal, pediatric, and adult mechanics and a filter to capture medication was attached to a realistic face model during spontaneous breathing or an endotracheal tube during conventional ventilation and high-frequency oscillator ventilator. Inhaled treprostinil was then nebulized with both the Tyvaso Inhalation System and vibrating mesh nebulizer, and the filter was analyzed via high-performance liquid chromatography. Testing was done in triplicate. Independent two-sample t tests were used to compare mean fine particle fraction and inhaled mass between devices. Analysis of variance with Tukey post hoc tests were used to compare within device differences. SETTING: Academic children's hospital aerosol research laboratory. MEASUREMENTS AND MAIN RESULTS: Fine particle fraction was not different between the Tyvaso Inhalation System and vibrating mesh nebulizer (0.78 ± 0.04 vs 0.77 ± 0.08, respectively; p = 0.79). The vibrating mesh nebulizer delivered the same or greater inhaled treprostinil than the Tyvaso Inhalation System in every simulated model and condition. When using the vibrating mesh nebulizer, delivery was highest when using high-frequency oscillator ventilator in the neonatal and pediatric models, and with the nebulizer in the distal position in the adult model. CONCLUSIONS: The vibrating mesh nebulizer is a suitable alternative to the Tyvaso Inhalation System for inhaled treprostinil delivery. Fine particle fraction is similar between devices, and vibrating mesh nebulizer delivery meets or exceeds delivery of the Tyvaso Inhalation System. Delivery for infants and children during high-frequency oscillator ventilator with the vibrating mesh nebulizer may result in higher than expected dosages.


Subject(s)
Antihypertensive Agents/administration & dosage , Drug Delivery Systems/instrumentation , Epoprostenol/analogs & derivatives , Hypertension, Pulmonary/therapy , Nebulizers and Vaporizers , Respiration, Artificial , Administration, Inhalation , Adult , Aerosols , Antihypertensive Agents/therapeutic use , Child , Child, Preschool , Combined Modality Therapy , Epoprostenol/administration & dosage , Epoprostenol/therapeutic use , Feasibility Studies , Humans , Infant, Newborn , Models, Anatomic , Particle Size , Vibration
13.
Oncotarget ; 8(15): 24679-24693, 2017 Apr 11.
Article in English | MEDLINE | ID: mdl-28160567

ABSTRACT

Ewing sarcoma (EwS) is the second most common bone cancer in children and adolescents with a high metastatic potential. EwS development is driven by a specific chromosomal translocation resulting in the generation of a chimeric EWS-ETS transcription factor, most frequently EWS-FLI1.Nicotinamide adenine dinucleotide (NAD) is a key metabolite of energy metabolism involved in cellular redox reactions, DNA repair, and in the maintenance of genomic stability. This study describes targeting nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD synthesis, by FK866 in EwS cells. Here we report that blocking NAMPT leads to exhaustive NAD depletion in EwS cells, followed by a metabolic collapse and cell death. Using conditional EWS-FLI1 knockdown by doxycycline-inducible shRNA revealed that EWS-FLI1 depletion significantly reduces the sensitivity of EwS cells to NAMPT inhibition. Consistent with this finding, a comparison of 7 EwS cell lines of different genotypes with 5 Non-EwS cell lines and mesenchymal stem cells revealed significantly higher FK866 sensitivity of EWS-ETS positive EwS cells, with IC50 values mostly below 1nM.Taken together, our data reveal evidence of an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of EwS cells and suggest NAMPT inhibition as a potential new treatment approach for Ewing sarcoma.


Subject(s)
Acrylamides/pharmacology , Cytokines/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Nicotinamide Phosphoribosyltransferase/antagonists & inhibitors , Oncogene Proteins, Fusion/metabolism , Piperidines/pharmacology , Proto-Oncogene Protein c-fli-1/metabolism , RNA-Binding Protein EWS/metabolism , Bone Neoplasms/drug therapy , Bone Neoplasms/enzymology , Bone Neoplasms/metabolism , Cell Line, Tumor , Cytokines/metabolism , Drug Resistance, Neoplasm , HeLa Cells , Humans , NAD/metabolism , Nicotinamide Phosphoribosyltransferase/metabolism , Sarcoma, Ewing/drug therapy , Sarcoma, Ewing/enzymology , Sarcoma, Ewing/metabolism , Sarcoma, Ewing/pathology
14.
Oncotarget ; 8(7): 10980-10993, 2017 Feb 14.
Article in English | MEDLINE | ID: mdl-28030800

ABSTRACT

MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3'UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing sarcoma. MiR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be among the top EWS-FLI1 activated miRNAs. Using a combination of AGO2 pull-down experiments by PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) and of RNAseq upon miRNA depletion by ectopic sponge expression, we aimed to identify the targetome of miR-17-92 in Ewing sarcoma. Intersecting both datasets we found an enrichment of PAR-CLIP hits for members of the miR-17-92 cluster in the 3'UTRs of genes up-regulated in response to mir-17-92 specific sponge expression. Strikingly, approximately a quarter of these genes annotate to the TGFB/BMP pathway, the majority mapping downstream of SMAD signaling. Testing for SMAD phosphorylation, we identify quiet but activatable TGFB signaling and cell autonomous activity of the BMP pathway resulting in the activation of the stemness regulatory transcriptional repressors ID1 and ID3. Taken together, our findings shed light on the complex miRegulatory landscape of Ewing Sarcoma pointing miR-17-92 as a key node connected to TGFB/BMP pathway.


Subject(s)
3' Untranslated Regions/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Bone Morphogenetic Proteins/genetics , Bone Morphogenetic Proteins/metabolism , Cell Line, Tumor , Genetic Predisposition to Disease/genetics , Humans , Mutation , Oligonucleotide Array Sequence Analysis , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Protein c-fli-1/genetics , RNA, Long Noncoding , RNA-Binding Protein EWS/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sarcoma, Ewing/genetics , Sarcoma, Ewing/metabolism , Sarcoma, Ewing/pathology , Sequence Analysis, RNA , Signal Transduction/genetics , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism
15.
FEBS Lett ; 590(14): 2063-75, 2016 07.
Article in English | MEDLINE | ID: mdl-27282934

ABSTRACT

Ewing sarcoma (ES) is an aggressive pediatric tumor driven by the fusion protein EWS-FLI1. We report that EWS-FLI1 suppresses TDO2-mediated tryptophan (TRP) breakdown in ES cells. Gene expression and metabolite analyses reveal an EWS-FLI1-dependent regulation of TRP metabolism. TRP consumption increased in the absence of EWS-FLI1, resulting in kynurenine and kynurenic acid accumulation, both aryl hydrocarbon receptor (AHR) ligands. Activated AHR binds to the promoter region of target genes. We demonstrate that EWS-FLI1 knockdown results in AHR nuclear translocation and activation. Our data suggest that EWS-FLI1 suppresses autocrine AHR signaling by inhibiting TDO2-catalyzed TRP breakdown.


Subject(s)
Autocrine Communication , Kynurenine/metabolism , Oncogene Proteins, Fusion/metabolism , Proto-Oncogene Protein c-fli-1/metabolism , RNA-Binding Protein EWS/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Signal Transduction , Tryptophan Oxygenase/metabolism , Tryptophan/metabolism , Cell Line , Humans , Kynurenine/genetics , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Protein c-fli-1/genetics , RNA-Binding Protein EWS/genetics , Receptors, Aryl Hydrocarbon/genetics , Tryptophan/genetics , Tryptophan Oxygenase/genetics
16.
Pulm Circ ; 6(1): 63-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27162615

ABSTRACT

Iloprost is a selective pulmonary vasodilator approved for inhalation by the Food and Drug Administration. Iloprost has been increasingly used in the management of critically ill neonates with hypoxic lung disease. This in vitro study was designed to test the hypothesis that aerosol drug delivery could be effectively administered to infants with both conventional ventilation and high-frequency oscillatory ventilation (HFOV). A neonatal test lung model configured with newborn lung mechanics was ventilated with a conventional ventilator and an HFOV with standard settings. A vibrating-mesh nebulizer was placed (1) proximal to the patient airway in the inspiratory limb between the humidifier probe and patient wye (conventional) as well as between the vent circuit and the endotracheal tube (ETT) for HFOV and (2) between the ventilator and humidifier (distal). Iloprost was nebulized in three separate runs using three new nebulizers in each of the circuit locations. A collecting filter was placed at the distal end of the ETT for each trial. Iloprost was quantified using high-performance liquid chromatography. The percentage of nominal dose delivered was greater with the nebulizer placed proximal to the airway for conventional ventilation (10.74% ± 2%) and HFOV (29% ± 2%) than with it placed in the distal position (2.96% ± 0.2% vs. 0.96% ± 0.8%, respectively; P < 0.05). Drug delivery in proximal position was nearly threefold greater during HFOV than during conventional ventilation. In conclusion, iloprost drug delivery was best achieved when the nebulizer was placed proximal to the patient airway during neonatal mechanical ventilation. Drug delivery appears to be more efficient during HFOV than during conventional ventilation.

17.
Clin Pharmacol Ther ; 100(1): 63-6, 2016 07.
Article in English | MEDLINE | ID: mdl-26850569

ABSTRACT

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding.


Subject(s)
Pharmacogenetics/organization & administration , Safety-net Providers/organization & administration , Vulnerable Populations , Academic Medical Centers/organization & administration , Humans , Medically Uninsured , Poverty
18.
PLoS One ; 10(7): e0132632, 2015.
Article in English | MEDLINE | ID: mdl-26161540

ABSTRACT

An ongoing question in paleoenvironmental reconstructions of the central African rainforest concerns the role that prehistoric metallurgy played in shaping forest vegetation. Here we report evidence of intensive iron-ore mining and smelting in forested regions of the northern Congo Basin dating to the late Holocene. Volumetric estimates on extracted iron-ore and associated slag mounds from prehistoric sites in the southern Central African Republic suggest large-scale iron production on par with other archaeological and historically-known iron fabrication areas. These data document the first evidence of intensive iron mining and production spanning approximately 90 years prior to colonial occupation (circa AD 1889) and during an interval of time that is poorly represented in the archaeological record. Additional site areas pre-dating these remains by 3-4 centuries reflect an earlier period of iron production on a smaller scale. Microbotanical evidence from a sediment core collected from an adjacent riparian trap shows a reduction in shade-demanding trees in concert with an increase in light-demanding species spanning the time interval associated with iron intensification. This shift occurs during the same time interval when many portions of the Central African witnessed forest transgressions associated with a return to moister and more humid conditions beginning 500-100 years ago. Although data presented here do not demonstrate that iron smelting activities caused widespread vegetation change in Central Africa, we argue that intense mining and smelting can have localized and potentially regional impacts on vegetation communities. These data further demonstrate the high value of pairing archeological and paleoenvironmental analyses to reconstruct regional-scale forest histories.


Subject(s)
Forests , Mining , Central African Republic , Congo , Humans , Metallurgy
19.
PLoS Curr ; 72015 Apr 30.
Article in English | MEDLINE | ID: mdl-25969795

ABSTRACT

Background. Mass ground movements (commonly referred to as 'landslides') are common natural hazards that can have significant economic, social and health impacts. They occur as single events, or as clusters, and are often part of 'disaster' chains, occurring secondary to, or acting as the precursor of other disaster events. Whilst there is a large body of literature on the engineering and geological aspects of landslides, the mortality and morbidity caused by landslides is less well documented. As far as we are aware, this is the first systematic review to examine the health impacts of landslides. Methods. The MEDLINE, EMBASE, CINAHL, SCOPUS databases and the Cochrane library were systematically searched to identify articles which considered the health impacts of landslides. Case studies, case series, primary research and systematic reviews were included. News reports, editorials and non-systematic reviews were excluded. Only articles in English were considered. The references of retrieved papers were searched to identify additional articles. Findings. 913 abstracts were reviewed and 143 full text articles selected for review. A total of 27 papers reporting research studies were included in the review (25 from initial search, 1 from review of references and 1 from personal correspondence). We found a limited number of studies on the physical health consequences of landslides. Only one study provided detail of the causes of mortality and morbidity in relation a landslide event. Landslides cause significant mental health impacts, in particular the prevalence of PTSD may be higher after landslides than other types of disaster, though these studies tend to be older with only 3 papers published in the last 5 years, with 2 being published 20 years ago, and diagnostic criteria have changed since they were produced. Discussion. We were disappointed at the small number of relevant studies, and the generally poor documentation of the health impacts of landslides. Mental health impacts were better documented, though some of the studies are now quite old. Further research on the health impacts of landslides needs to be undertaken to support those responding to landslide disasters and to aid disaster risk mitigation advocacy.

20.
J Postgrad Med ; 61(2): 92-4, 2015.
Article in English | MEDLINE | ID: mdl-25766340

ABSTRACT

BACKGROUND: Surgical care is an essential component of health care of children worldwide. Incidences of congenital anomalies, trauma, cancers and acquired diseases continue to rise and along with that the impact of surgical intervention on public health system also increases. It then becomes essential that the surgical teams make the procedures safe and error proof. The World Health Organization (WHO) has instituted the surgical checklist as a global initiative to improve surgical safety. AIMS: To assess the acceptance, application and adherence to the WHO Safe Surgery Checklist in Pediatric Surgery Practice at a university teaching hospital. MATERIALS AND METHODS: In a prospective study, spanning 2 years, the checklist was implemented for all patients who underwent operative procedures under general anesthesia. The checklist identified three phases of an operation, each corresponding to a specific period in the normal flow of work: Before the induction of anesthesia ("sign in"), before the skin incision ("time out") and before the patient leaves the operating room ("sign out"). In each phase, an anesthesiologist,-"checklist coordinator," confirmed that the anesthesia, surgery and nursing teams have completed the listed tasks before proceeding with the operation and exit. The checklist was used for 3000 consecutive patients. RESULTS: No major perioperative errors were noted. In 54 (1.8%) patients, children had the same names and identical surgical procedure posted on the same operation list. The patient identification tag was missing in four (0.1%) patients. Mention of the side of procedures was missing in 108 (3.6%) cases. In 0.1% (3) of patients there was mix up of the mention of side of operation in the case papers and consent forms. In 78 (2.6%) patients, the consent form was not signed by parents/guardians or the side of the procedure was not quoted. Antibiotic orders were missing in five (0.2%) patients. In 12 (0.4%) cases, immobilization of the patients was suboptimal, which led to displacement of diathermy grounding pad. In 54 (1.8%) patients, the checklist was not used at all. In 76 (2.5%) patients the checklist was found to be incompletely filled. CONCLUSIONS: Our study supports the use of the checklist as an essential safety tool and reinforcement of the same. The checklist may act as a valuable prompt to focus the team, to ensure that even the simple things have been cared for.


Subject(s)
Checklist/statistics & numerical data , Operating Rooms/standards , Patient Safety , Practice Guidelines as Topic , Surgical Procedures, Operative/standards , Adult , Child , Child, Preschool , Female , Hospitals, Teaching , Humans , Male , Medical Errors/prevention & control , Operating Rooms/organization & administration , Pediatrics , Perioperative Care/standards , Physician-Patient Relations , Practice Patterns, Physicians' , Prospective Studies , Safety Management/methods , World Health Organization
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