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1.
Paediatr Anaesth ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655874

RESUMO

Australia and New Zealand are two countries in the Southern Pacific region. They share many pediatric anesthesia similarities in terms of medical organizational systems, education, training, and research, however there are important differences between the two nations in relation to geography, the First Nations populations and the history of colonization. While the standards for pediatric anesthesia and the specialty training requirements are set by the Australian and New Zealand College of Anesthetists and the Society for Pediatric Anesthesia in New Zealand and Australia, colonization has created distinct challenges that each nation now faces in order to improve the anesthetic care of its pediatric population. Australia generally has a high standard of living and good access to health care; disparities exist for First Nations People and for those living in rural or remote areas. Two influences have shaped training within New Zealand over the past 40 years; establishment of a national children's hospital in 1990 and, more importantly, acknowledgement that the First Nations people of New Zealand (Maori) have suffered because of failure to recognize their rights consequent to establishing a partnership treaty between Maori and the British Crown in 1840. Health inequities among Maori in New Zealand and First Nations People in Australia have implications for the health system, culturally appropriate approaches to treatment, and the importance of having an appreciation of First Nations people's history and culture, language, family structure, and cultural safety. Trainees in both countries need to be adequately supported in these areas in order for the sub-specialty of pediatric anesthesia to develop further and improve the anesthetic and surgical outcomes of our children.

2.
Br J Anaesth ; 132(5): 886-898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38336513

RESUMO

BACKGROUND: Digital health interventions offer a promising approach for monitoring during postoperative recovery. However, the effectiveness of these interventions remains poorly understood, particularly in children. The objective of this study was to assess the efficacy of digital health interventions for postoperative recovery in children. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with the use of automation tools for searching and screening. We searched five electronic databases for randomised controlled trials or non-randomised studies of interventions that utilised digital health interventions to monitor postoperative recovery in children. The study quality was assessed using Cochrane Collaboration's Risk of Bias tools. The systematic review protocol was prospectively registered with PROSPERO (CRD42022351492). RESULTS: The review included 16 studies involving 2728 participants from six countries. Tonsillectomy was the most common surgery and smartphone apps (WeChat) were the most commonly used digital health interventions. Digital health interventions resulted in significant improvements in parental knowledge about the child's condition and satisfaction regarding perioperative instructions (standard mean difference=2.16, 95% confidence interval 1.45-2.87; z=5.98, P<0.001; I2=88%). However, there was no significant effect on children's pain intensity (standard mean difference=0.09, 95% confidence interval -0.95 to 1.12; z=0.16, P=0.87; I2=98%). CONCLUSIONS: Digital health interventions hold promise for improving parental postoperative knowledge and satisfaction. However, more research is needed for child-centric interventions with validated outcome measures. Future work should focus development and testing of user-friendly digital apps and wearables to ease the healthcare burden and improve outcomes for children. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022351492).


Assuntos
Saúde Digital , Aplicativos Móveis , Humanos , Revisões Sistemáticas como Assunto
4.
Anesth Analg ; 137(4): 819-829, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471292

RESUMO

Nitrous oxide is a useful inhaled analgesic. Due to its high global warming potential and ozone-depleting properties, the nitrous oxide emissions related to health care are being increasingly scrutinized. In this narrative review, we will discuss the clinical uses of nitrous oxide relevant to anesthetists, in addition to its contribution as a greenhouse gas. Using available data from Australia, we will explore potential strategies for reducing the impact of those emissions, which are likely to be applicable in other countries. These include destruction of captured nitrous oxide, minimizing nitrous oxide waste and reducing clinical use. Anesthesia clinicians are well placed to raise awareness with colleagues and consumers regarding the environmental impact of nitrous oxide and to promote cleaner alternatives. Reducing use is likely to be the most promising reduction strategy without large-scale changes to infrastructure and subsequent delay in action.


Assuntos
Gases de Efeito Estufa , Óxido Nitroso , Óxido Nitroso/efeitos adversos , Óxido Nitroso/análise , Austrália , Gases de Efeito Estufa/efeitos adversos , Aquecimento Global/prevenção & controle , Atenção à Saúde
5.
Trials ; 24(1): 446, 2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37422667

RESUMO

BACKGROUND: Children undergoing anaesthetic induction experience peri-operative anxiety associated with negative outcomes including emergence delirium, short- and long-term maladaptive behaviour and increased postoperative analgesic requirements. This stems from children's limited ability to communicate, cope, and regulate intense emotions, leading to high dependency on parental emotional regulation. Previous interventions including video modelling, education and distraction techniques before and during anaesthetic induction have demonstrated significant reduction of anxiety levels. No existing interventions combines evidenced-based psychoeducation video with distraction techniques to support parents to moderate peri-operative anxiety. This study aims to test the efficacy of the Take5 video (now referred to as 'Take5'), a short and cost-efficient intervention for child peri-operative anxiety. METHODS: A randomised, controlled, superiority trial of Take5 compared to standard care. Take5 was developed by paediatric anaesthetists, child psychologists and a consumer panel of parents of children who had experienced surgery and anaesthesia. Children aged 3-10 years presenting for elective surgery at a quaternary paediatric facility will be randomly allocated to the intervention group or standard care. Intervention group parents will be shown Take5 prior to accompanying their child for anaesthesia induction. Primary outcomes include child and parent anxiety at induction, measured by the Modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF), the Peri-operative Adult-Child Behavior Interaction Scale (PACBIS) and the Induction Compliance Checklist (ICC). Secondary outcomes include post-operative pain, emergence delirium, parental satisfaction, cost-effectiveness, parent and child psychological well-being at 3 months post procedure and video intervention acceptability. DISCUSSION: Perioperative anxiety is associated with negative outcome in children including higher pharmacological intervention, delayed procedures, and poor post-recovery outcomes resulting in financial burden on health systems. Current strategies minimising paediatric procedural distress are resource-intensive and have been inconsistent in reducing anxiety and negative postoperative outcomes. The Take5 video is an evidence-driven resource that is designed to prepare and empower parents. The success of Take5 will be evaluated by measuring differences in patient (acute and 3-month), family (satisfaction, acceptability), clinician (feasibility) and health service (cost) outcomes, with each anticipated to benefit children. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry (ACTRN12621001337864) and Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC/21/QCHQ/73894).


Assuntos
Anestésicos , Delírio do Despertar , Adulto , Criança , Humanos , Austrália , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/prevenção & controle , Pais/psicologia , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Eur Urol Oncol ; 6(3): 303-310, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37012102

RESUMO

BACKGROUND: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. OBJECTIVE: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. RESULTS AND LIMITATIONS: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). CONCLUSIONS: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. PATIENT SUMMARY: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer.


Assuntos
Neoplasias da Próstata , Reirradiação , Masculino , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Prostatectomia/efeitos adversos
7.
J Control Release ; 357: 655-668, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37080489

RESUMO

The wide prevalence of BRAF mutations in diagnosed melanomas drove the clinical advancement of BRAF inhibitors in combination with immune checkpoint blockade for treatment of advanced disease. However, deficits in therapeutic potencies and safety profiles motivate the development of more effective strategies that improve the combination therapy's therapeutic index. Herein, we demonstrate the benefits of a locoregional chemoimmunotherapy delivery system, a novel thermosensitive hydrogel comprised of gelatin and Pluronic® F127 components already widely used in humans in both commercial and clinical products, for the co-delivery of a small molecule BRAF inhibitor with immune checkpoint blockade antibody for the treatment of BRAF-mutated melanoma. In vivo evaluation of administration route and immune checkpoint target effects revealed intratumoral administration of antagonistic programmed cell death protein 1 antibody (aPD-1) lead to potent antitumor therapy in combination with BRAF inhibitor vemurafenib. The thermosensitive F127-g-Gelatin hydrogel that was evaluated in multiple murine models of BRAF-mutated melanoma that facilitated prolonged local drug release within the tumor (>1 week) substantially improved local immunomodulation, tumor control, rates of tumor response, and animal survival. Thermosensitive F127-g-Gelatin hydrogels thus improve upon the clinical benefits of vemurafenib and aPD-1 in a locoregional chemoimmunotherapy approach for the treatment of BRAF-mutated melanoma.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas B-raf , Humanos , Animais , Camundongos , Vemurafenib/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Hidrogéis/uso terapêutico , Gelatina , Preparações de Ação Retardada/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Inibidores de Proteínas Quinases , Mutação
8.
Sci Adv ; 9(8): eabq0435, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36827374

RESUMO

Dysfunction of collecting lymphatic vessel pumping is associated with an array of pathologies. S-(-)-Bay K8644 (BayK), a small-molecule agonist of L-type calcium channels, improves vessel contractility ex vivo but has been left unexplored in vivo because of poor lymphatic access and risk of deleterious off-target effects. When formulated within lymph-draining nanoparticles (NPs), BayK acutely improved lymphatic vessel function, effects not seen from treatment with BayK in its free form. By preventing rapid drug access to the circulation, NP formulation also reduced BayK's dose-limiting side effects. When applied to a mouse model of lymphedema, treatment with BayK formulated in lymph-draining NPs, but not free BayK, improved pumping pressure generated by intact lymphatic vessels and tissue remodeling associated with the pathology. This work reveals the utility of a lymph-targeting NP platform to pharmacologically enhance lymphatic pumping in vivo and highlights a promising approach to treating lymphatic dysfunction.


Assuntos
Vasos Linfáticos , Camundongos , Animais , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Modelos Animais de Doenças , Pressão
10.
Paediatr Anaesth ; 33(3): 229-235, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36371675

RESUMO

BACKGROUND: Early and delayed behavioral changes are well recognized after anesthesia. Intravenous anesthesia may prevent emergence delirium. However, it has not been evaluated as a preventive strategy for delayed postoperative behavior changes. AIMS: We aimed to determine whether intravenous anesthesia is effective at reducing postoperative behavior changes in children undergoing ambulatory endoscopic procedures when compared to inhalation anesthesia. METHODS: This randomized, double-blinded controlled trial was approved by the local IRB. Children aged 1-12 years who underwent ambulatory endoscopic procedures were recruited. Preoperative anxiety was evaluated through the modified Yale Preoperative Anxiety Scale. All children underwent face mask inhalation induction with sevoflurane. After a peripheral line was placed, each child was allocated to sevoflurane or propofol maintenance. Emergence delirium was evaluated through the Pediatric Anesthesia Emergence Delirium scale. The child was discharged home, and behavioral changes were assessed through the Posthospitalization Behavior Questionnaire for Ambulatory Surgery on Days 1, 7, and 14. RESULTS: Overall, 175 children were enrolled. On Day 1 after the procedure, 57 children presented at least one negative behavior. On Days 7 and 14, 49 and 44 children presented at least one negative behavior, respectively. The median number of negative behaviors was similar between the groups. Post hoc analyses showed a moderate correlation between emergence delirium and negative postoperative behavior on Day 7 (r = .34; p = <.001) and an increase of 3.31 (95% CI 1.90; 4.36 p < .001) points in the mean summed score of new negative behaviors for individuals with emergence delirium. CONCLUSION: The incidence of postoperative behavior changes in children undergoing ambulatory endoscopic procedures was similar when comparing intravenous with inhalation anesthesia. Children who experience emergence delirium might show a greater incidence of negative postoperative behavior changes.


Assuntos
Anestésicos Inalatórios , Delírio do Despertar , Éteres Metílicos , Criança , Humanos , Sevoflurano , Delírio do Despertar/epidemiologia , Delírio do Despertar/prevenção & controle , Delírio do Despertar/etiologia , Anestesia por Inalação/efeitos adversos , Período de Recuperação da Anestesia
11.
Proc Natl Acad Sci U S A ; 119(27): e2201139119, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35759667

RESUMO

The Sample Analysis at Mars instrument stepped combustion experiment on a Yellowknife Bay mudstone at Gale crater, Mars revealed the presence of organic carbon of Martian and meteoritic origins. The combustion experiment was designed to access refractory organic carbon in Mars surface sediments by heating samples in the presence of oxygen to combust carbon to CO2. Four steps were performed, two at low temperatures (less than ∼550 °C) and two at high temperatures (up to ∼870 °C). More than 950 µg C/g was released at low temperatures (with an isotopic composition of δ13C = +1.5 ± 3.8‰) representing a minimum of 431 µg C/g indigenous organic and inorganic Martian carbon components. Above 550 °C, 273 ± 30 µg C/g was evolved as CO2 and CO (with estimated δ13C = -32.9‰ to -10.1‰ for organic carbon). The source of high temperature organic carbon cannot be definitively confirmed by isotopic composition, which is consistent with macromolecular organic carbon of igneous origin, meteoritic infall, or diagenetically altered biomass, or a combination of these. If from allochthonous deposition, organic carbon could have supported both prebiotic organic chemistry and heterotrophic metabolism at Gale crater, Mars, at ∼3.5 Ga.

12.
Nat Commun ; 13(1): 1479, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35304456

RESUMO

Due to their autosynchronous roles in shaping the anti-tumor immune response, complex immune regulatory networks acting both locally within the tumor microenvironment as well as in its draining lymph nodes play critical roles in the cancer immunotherapy response. We describe herein a thermosensitive co-polymer hydrogel system formed from biocompatible polymers gelatin and Pluronic® F127 that are widely used in humans to enable the sustained release of a nitric oxide donor and antibody blocking immune checkpoint cytotoxic T-lymphocyte-associated protein-4 for efficient and durable anti-tumor immunotherapy. By virtue of its unique gel formation and degradation properties that sustain drug retention at the tumor tissue site for triggered release by the tumor microenvironment and formation of in situ micelles optimum in size for lymphatic uptake, this rationally designed thermosensitive hydrogel facilitates modulation of two orthogonal immune signaling networks relevant to the regulation of the anti-tumor immune response to improve local and abscopal effects of cancer immunotherapy.


Assuntos
Hidrogéis , Micelas , Humanos , Hidrogéis/química , Imunoterapia , Doadores de Óxido Nítrico , Poloxâmero
13.
Paediatr Anaesth ; 32(1): 62-66, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34729869

RESUMO

BACKGROUND: A contemporary, well-validated instrument for the measurement of behavior change in children after general anesthesia is lacking. The Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) has been developed as an updated version of the original Post Hospitalization Behavior Questionnaire (PHBQ) to better reflect the current patient population and modern anesthetic practices. AIMS: To assess the reliability of the PHBQ-AS and determine concurrent validity with another measure of child behavior, the Strength and Difficulties Questionnaire (SDQ). METHODS: We compared the PHBQ-AS with the SDQ in 248 children presenting for day-case surgery. A baseline SDQ measurement was taken prior to surgery, and then, both scales were administered on days 3, 14, and 28 postsurgery. RESULTS: The PHBQ-AS demonstrated good reliability in terms of internal consistency with a Cronbach's alpha of 0.79 and split-half correlation with Spearman Brown adjustment of 0.85. There was weak correlation with the SDQ on day 3 postoperatively (Pearson's r = 0.201), moderate correlation on day 14 (Pearson's r = 0.421), and weak-to-moderate correlation on day 28 (Pearson's r = 0.340). A cut-off score of 3.2 on the PHBQ-AS for the diagnosis of negative behavior demonstrated equivalence with the SDQ results; however, the SDQ results remained relatively constant throughout the study period and reflected the expected rate of increased risk of problem behavior in children. CONCLUSIONS: The PHBQ-AS showed good reliability but only had weak-to-moderate correlation with another measure of child behavior, the SDQ. Further validation is required before the PHBQ-AS is used for the routine measurement of behavior change in children after anesthesia, or alternatively, a new instrument needs to be developed in order for research to advance in this area.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Transtornos do Comportamento Infantil , Criança , Comportamento Infantil , Transtornos do Comportamento Infantil/diagnóstico , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
14.
Pediatr Blood Cancer ; 69(3): e29513, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34971078

RESUMO

BACKGROUND: Minimal residual disease (MRD) measured on end-of-induction bone marrow (BM) is the most important biomarker for guiding therapy in pediatric acute lymphoblastic leukemia (ALL). Due to limited sensitivity of current approaches, peripheral blood (PB) is not a reliable source for identifying patients needing treatment changes. We sought to determine if high-throughput sequencing (HTS) (next-generation sequencing) of rearranged immunoglobulin and T-cell receptor genes can overcome this and be used to measure MRD in PB. PROCEDURE: We employed a quantitative HTS approach to accurately measure MRD from one million cell equivalents of DNA from 17 PB samples collected at day 29 after induction therapy in patients with precursor B-cell ALL. We compared these results to the gold-standard real-time PCR result obtained from their paired BM samples, median follow-up 49 months. RESULTS: With the increased sensitivity, detecting up to one abnormal cell in a million normal cells, we were able to detect MRD in the PB by HTS in all those patients requiring treatment intensification (MRD ≥ 0.005% in BM). CONCLUSION: This is proof of principle that using the increased sensitivity of HTS, PB can be used to measure MRD and stratify children with ALL. The method is cost effective, rapid, accurate, and reproducible, with inherent advantages in children. Importantly, increasing the frequency testing by PB as opposed to intermittent BM sampling may allow extension of the dynamic range of MRD, giving a more complete picture of the kinetics of disease remission while improving relapse prediction and speed of detection.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Estudos de Viabilidade , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Células Precursoras de Linfócitos B , Estudos Prospectivos
15.
Semin Immunol ; 56: 101534, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34836772

RESUMO

Lymph nodes are secondary lymphoid tissues in the body that facilitate the co-mingling of immune cells to enable and regulate the adaptive immune response. They are also tissues implicated in a variety of diseases, including but not limited to malignancy. The ability to access lymph nodes is thus attractive for a variety of therapeutic and diagnostic applications. As nanotechnologies are now well established for their potential in translational biomedical applications, their high relevance to applications that involve lymph nodes is highlighted. Herein, established paradigms of nanocarrier design to enable delivery to lymph nodes are discussed, considering the unique lymph node tissue structure as well as lymphatic system physiology. The influence of delivery mechanism on how nanocarrier systems distribute to different compartments and cells that reside within lymph nodes is also elaborated. Finally, current advanced nanoparticle technologies that have been developed to enable lymph node delivery are discussed.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Imunidade Adaptativa , Humanos , Linfonodos , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanotecnologia
16.
Biomaterials ; 279: 121184, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34678650

RESUMO

Multiple small molecule immune modulators have been identified as synergistic with immune checkpoint blockade (ICB) in their effects on T lymphocytes, but are limited in their successful application to combination cancer immunotherapy due to their short in vivo retention and lack of affinity for T cells. We engineered an antibody-nanoparticle conjugate (ANC) platform consisting of 30 nm polymer nanoparticles that, due to their size and formulation, efficiently distribute after administration to lymph nodes, tissues highly enriched in lymphocytes that contribute to tumor control mediated by ICB. Displaying monoclonal antibodies against surface-expressed T cell markers, NP delivery in vivo to circulating and lymph node-resident lymphocytes was substantially enhanced, as was delivery of small molecules formulated into the NP by passive encapsulation. Using ICB monoclonal antibodies as both targeting moiety and signal-blocking therapeutic, ANCs improved the local and systemic anti-tumor effects of small molecule TGFß receptor 1 inhibitor and an adenosine 2A antagonist when administered either locoregionally or systemically into the circulation in two syngeneic, aggressive tumor models, slowing tumor growth and prolonging animal survival. As these benefits were lost in the absence of ANC targeting, co-formulation strategies enabling the targeted co-delivery of multiple immunotherapeutics to T lymphocytes have high potential to improve ICB cancer immunotherapy by concurrent inhibition of non-redundant suppressive pathways.


Assuntos
Nanopartículas , Neoplasias , Preparações Farmacêuticas , Animais , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias/tratamento farmacológico , Linfócitos T
17.
Drug Deliv Transl Res ; 11(6): 2328-2343, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34165731

RESUMO

Lymph nodes (LNs) are tissues of the immune system that house leukocytes, making them targets of interest for a variety of therapeutic immunomodulation applications. However, achieving accumulation of a therapeutic in the LN does not guarantee equal access to all leukocyte subsets. LNs are structured to enable sampling of lymph draining from peripheral tissues in a highly spatiotemporally regulated fashion in order to facilitate optimal adaptive immune responses. This structure results in restricted nanoscale drug delivery carrier access to specific leukocyte targets within the LN parenchyma. Herein, a framework is presented to assess the manner in which lymph-derived macromolecules and particles are sampled in the LN to reveal new insights into how therapeutic strategies or drug delivery systems may be designed to improve access to dLN-resident leukocytes. This summary analysis of previous reports from our group assesses model nanoscale fluorescent tracer association with various leukocyte populations across relevant time periods post administration, studies the effects of bioactive molecule NO on access of lymph-borne solutes to dLN leukocytes, and illustrates the benefits to leukocyte access afforded by lymphatic-targeted multistage drug delivery systems. Results reveal trends consistent with the consensus view of how lymph is sampled by LN leukocytes resulting from tissue structural barriers that regulate inter-LN transport and demonstrate how novel, engineered delivery systems may be designed to overcome these barriers to unlock the therapeutic potential of LN-resident cells as drug delivery targets.


Assuntos
Vasos Linfáticos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Leucócitos , Linfonodos
18.
BMJ Open ; 11(4): e042475, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853797

RESUMO

INTRODUCTION: Peripherally inserted central catheters (PICCs) are vital for the delivery of medical therapies, but up to 30% of PICCs are associated with complications such as deep vein thrombosis or infection. The integration of antimicrobial and hydrophobic catheter materials, and pressure-activated valves, into polyurethane PICCs are innovations designed to prevent infective and/or thrombotic complications. METHODS AND ANALYSIS: A multicentre, parallel group, superiority randomised controlled trial with two experimental arms ((1) hydrophobic PICC (with pressure-activated valve); (2) chlorhexidine gluconate-impregnated PICC (with external clamp)) and one control group ((3) conventional polyurethane PICC (with external clamp)). Recruitment of 1098 adult and paediatric patients will take place over 2 years at three tertiary-referral hospitals in Queensland, Australia. Patients are eligible for inclusion if their PICC is to be inserted for medical treatment, with a vascular size sufficient to support a 4-Fr PICC or larger, and with informed consent. The primary outcome is PICC failure, a composite of thrombotic (venous thrombosis, breakage and occlusion) and infective complications (PICC-associated bloodstream infection and local infection). Secondary outcomes include: all-cause PICC complication; thrombotic complications; infective complications; adverse events (local or systemic reaction); PICC dwell time; patient/parent satisfaction; and healthcare costs. Differences between both intervention groups and the control group will be compared using Cox proportional hazards regression. Effect estimates will be presented as HRs with corresponding 95% CI. ETHICS AND DISSEMINATION: Ethical approval from Queensland Health (HREC/QCHQ/48682) and Griffith University (Ref. No. 2019/094). Results will be published. TRIAL REGISTRATION NUMBER: ACTRN12619000022167.


Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Adulto , Austrália , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Criança , Humanos , Estudos Multicêntricos como Assunto , Queensland , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
19.
Paediatr Anaesth ; 31(4): 429-435, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33405250

RESUMO

BACKGROUND: Hypoactive delirium is present when an awake child is unaware of his or her surroundings, is unable to focus attention, and appears quiet and withdrawn. This condition has been well-described in the intensive care setting but has not been extensively studied in the immediate post-anesthetic period. AIM: To determine if hypoactive emergence delirium occurs in the recovery unit of a pediatric hospital, and if so, what proportion of emergence delirium is hypoactive in nature. METHODS: We conducted an observational study using the Cornell Assessment of Pediatric Delirium in a cohort of 4424 children recovered at a tertiary pediatric hospital. The incidence of emergence delirium detected using the Pediatric Anesthetic Emergence Delirium (PAED) scale was also recorded for comparison. RESULTS: There were 74 cases of emergence delirium detected during the study period using the Cornell Assessment of Pediatric Delirium (1.7%). Only 57 cases were detected using the Pediatric Anesthetic Emergence Delirium scale. The additional 17 cases detected using the Cornell Assessment of Pediatric Dlirium represent cases of hypoactive delirium. In this cohort of pediatric patients, 23% of all cases of emergence delirium were hypoactive in nature. CONCLUSION: The significance of hypoactive delirium in this population is unknown; however, previous studies have shown that emergence delirium can result in post-operative behavior changes and may affect compliance with future episodes of care. However, hypoactive delirium is often missed without active screening. The prevalence detected in this study therefore suggests hypoactive delirium warrants further investigation.


Assuntos
Anestesia , Delírio , Delírio do Despertar , Anestesia/efeitos adversos , Período de Recuperação da Anestesia , Criança , Delírio/induzido quimicamente , Delírio/diagnóstico , Delírio/epidemiologia , Delírio do Despertar/diagnóstico , Delírio do Despertar/epidemiologia , Feminino , Hospitais Pediátricos , Humanos , Masculino
20.
Paediatr Anaesth ; 31(3): 323-329, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33280199

RESUMO

BACKGROUND: Barrier techniques, such as plastic sheets or intubation boxes, are purported to offer additional protection for healthcare workers. AIMS: To assess the functionality, perceived safety, droplet protection, and aerosol protection of several barrier techniques. METHODS: Firstly, a simulation study with 12 different laryngoscopists was conducted to assess the time taken to perform an intubation (via direct laryngoscopy, via video laryngoscopy, and via a bougie) with four different barrier techniques (personal protective equipment only, a plastic sheet, a tented plastic sheet, and an intubation box). Secondly, a cough at the time of intubation was simulated using ultraviolet dye to assess the spread of droplets; and thirdly, smoke was used to assess the spread of aerosols. RESULTS: Intubation time using the box was noninferior to using no barrier. Based on subjective ratings by the laryngoscopists, the most functional technique was no barrier followed by the intubation box, then the tented sheet, and then the plastic sheet. The technique that conferred the highest feeling of safety to the laryngoscopists was the intubation box, followed by the tented sheet, then no barrier, and then the plastic sheet. All the barriers prevented the ultraviolet dye contaminating the head and torso of the laryngoscopist. Smoke remained within the intubation box if plastics sheets were used to cover the openings and suction was ineffective at clearing it. With no barrier in place, smoke was effectively cleared away from the patient in a theater with laminar flow but tended to spread up toward the laryngoscopist in a room without laminar flow. CONCLUSIONS: A well-designed intubation box is an effective barrier against droplets and is noninferior to no barrier in relation to intubation time. However, a box interferes with laminar flow in theaters with formal ventilation systems and may result in accumulation of aerosols if it is completely enclosed.


Assuntos
Anestésicos , COVID-19 , Criança , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Intubação Intratraqueal , SARS-CoV-2
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