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1.
Pediatr Blood Cancer ; 71(7): e31041, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38715224

RESUMO

International and national oncofertility networks, including the US-led Oncofertility Consortium, FertiProtekt, and the Danish Network, have played pivotal roles in advancing the discipline of oncofertility over the last decade. Many other countries lack a shared approach to pediatric oncofertility health service delivery. This study aims to describe baseline oncofertility practices at Australian New Zealand Children's Haematology/Oncology Group centers in 2019-2021, describe binational priorities for care, and propose a 5-year action plan for best practice to be implemented by the newly formed Australian New Zealand Consortium in Children, Adolescents, and Young Adults (CAYA) Oncofertility (ANZCO).


Assuntos
Preservação da Fertilidade , Neoplasias , Humanos , Adolescente , Nova Zelândia , Preservação da Fertilidade/métodos , Criança , Neoplasias/terapia , Neoplasias/complicações , Adulto Jovem , Feminino , Austrália , Masculino , Adulto
2.
Nurse Educ Pract ; 75: 103909, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38308946

RESUMO

AIM: This project explored whether a nurse practitioner led mobile paediatric screening service in early learning centres could incorporate allied health and nursing students and develop their confidence in interprofessional collaboration. BACKGROUND: Interprofessional collaboration is essential for health professionals across all contexts of care, including early childhood screening and intervention that enables children to thrive. METHODS: This multi-methods study (pre-test/post-test design) was conducted with nursing, physiotherapy, occupational therapy and nutrition and dietetics students attending clinical placement within the nurse practitioner led mobile paediatric service. Data were collected via pre and post placement surveys (ISVS-21) and post placement semi-structured interviews. RESULTS: Twelve students participated from July to December 2022. Survey findings demonstrated students improved inter-professional socialisation and readiness, supported by qualitative findings that uncovered unique mechanisms for how positive experiences were achieved. Unique pedagogical elements included 1) the nurse practitioner's professional attributes and 2) the mobile nature of the service leveraging learning opportunities within the shared commute. CONCLUSIONS: This study provides proof-of-concept of a placement model that facilitates interprofessional collaboration in nursing and allied health students. Further research should explore longer-term outcomes and scalability.


Assuntos
Profissionais de Enfermagem , Estudantes de Enfermagem , Pré-Escolar , Criança , Humanos , Educação Interprofissional , Aprendizagem , Pessoal Técnico de Saúde , Relações Interprofissionais
3.
Eur Radiol ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388716

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism. AIM: The aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC. METHODS: We conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB-IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [18F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV)). RESULTS: Patients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUVmax, SUVmean, SUVpeak and SULpeak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58-0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS. CONCLUSION: This study demonstrated the association of SUV-based [18F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%. CLINICAL RELEVANCE STATEMENT: Whilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies. TRIAL REGISTRATION: Non-applicable KEY POINTS: • Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic. • SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression. • These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram.

4.
Sci Transl Med ; 15(708): eabc8226, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37556557

RESUMO

Gene therapy for kidney diseases has proven challenging. Adeno-associated virus (AAV) is used as a vector for gene therapy targeting other organs, with particular success demonstrated in monogenic diseases. We aimed to establish gene therapy for the kidney by targeting a monogenic disease of the kidney podocyte. The most common cause of childhood genetic nephrotic syndrome is mutations in the podocyte gene NPHS2, encoding podocin. We used AAV-based gene therapy to rescue this genetic defect in human and mouse models of disease. In vitro transduction studies identified the AAV-LK03 serotype as a highly efficient transducer of human podocytes. AAV-LK03-mediated transduction of podocin in mutant human podocytes resulted in functional rescue in vitro, and AAV 2/9-mediated gene transfer in both the inducible podocin knockout and knock-in mouse models resulted in successful amelioration of kidney disease. A prophylactic approach of AAV 2/9 gene transfer before induction of disease in conditional knockout mice demonstrated improvements in albuminuria, plasma creatinine, plasma urea, plasma cholesterol, histological changes, and long-term survival. A therapeutic approach of AAV 2/9 gene transfer 2 weeks after disease induction in proteinuric conditional knock-in mice demonstrated improvement in urinary albuminuria at days 42 and 56 after disease induction, with corresponding improvements in plasma albumin. Therefore, we have demonstrated successful AAV-mediated gene rescue in a monogenic renal disease and established the podocyte as a tractable target for gene therapy approaches.


Assuntos
Nefropatias , Síndrome Nefrótica , Camundongos , Humanos , Animais , Síndrome Nefrótica/genética , Síndrome Nefrótica/terapia , Dependovirus/genética , Albuminúria , Modelos Genéticos , Terapia Genética/métodos , Modelos Animais de Doenças , Camundongos Knockout , Vetores Genéticos
5.
PLoS One ; 18(4): e0285122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37104298

RESUMO

BACKGROUND: Decision impact studies have become increasingly prevalent in genomic medicine, particularly in cancer research. Such studies are designed to provide evidence of clinical utility for genomic tests by evaluating their impact on clinical decision-making. This paper offers insights into understanding of the origins and intentions of these studies through an analysis of the actors and institutions responsible for the production of this new type of evidence. METHODS: We conducted bibliometric and funding analyses of decision impact studies in genomic medicine research. We searched databases from inception to June 2022. The datasets used were primarily from Web of Science. Biblioshiny, additional R-based applications, and Microsoft Excel were used for publication, co-authorship and co-word analyses. RESULTS: 163 publications were included for the bibliometric analysis; a subset of 125 studies were included for the funding analysis. Included publications started in 2010 and increased steadily over time. Decision impact studies were primarily produced for proprietary genomic assays for use in cancer care. The author and affiliate analyses reveal that these studies were produced by 'invisible colleges' of researchers and industry actors with collaborations focused on producing evidence for proprietary assays. Most authors had an industry affiliation, and the majority of studies were funded by industry. While studies were conducted in 22 countries, the majority had at least one author from the USA. DISCUSSION: This study is a critical step in understanding the role of industry in the production of new types of research. Based on the data collected, we conclude that decision impact studies are industry-conceived and -produced evidence. The findings of this study demonstrate the depth of industry involvement and highlight a need for further research into the use of these studies in decision-making for coverage and reimbursement.


Assuntos
Pesquisa Biomédica , Medicina Genômica , Bibliometria , Indústrias
6.
PLoS One ; 18(3): e0280582, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36897859

RESUMO

BACKGROUND: Decision impact studies have become increasingly prevalent in cancer prognostic research in recent years. These studies aim to evaluate the impact of a genomic test on decision-making and appear to be a new form of evidence of clinical utility. The objectives of this review were to identify and characterize decision impact studies in genomic medicine in cancer care and categorize the types of clinical utility outcomes reported. METHODS: We conducted a search of four databases, Medline, Embase, Scopus and Web of Science, from inception to June 2022. Empirical studies that reported a "decision impact" assessment of a genomic assay on treatment decisions or recommendations for cancer patients were included. We followed scoping review methodology and adapted the Fryback and Thornbury Model to collect and analyze data on clinical utility. The database searches identified 1803 unique articles for title/abstract screening; 269 articles moved to full-text review. RESULTS: 87 studies met inclusion criteria. All studies were published in the last 12 years with the majority for breast cancer (72%); followed by other cancers (28%) (lung, prostate, colon). Studies reported on the impact of 19 different proprietary (18) and generic (1) assays. Across all four levels of clinical utility, outcomes were reported for 22 discrete measures, including the impact on provider/team decision-making (100%), provider confidence (31%); change in treatment received (46%); patient psychological impacts (17%); and costing or savings impacts (21%). Based on the data synthesis, we created a comprehensive table of outcomes reported for clinical utility. CONCLUSIONS: This scoping review is a first step in understanding the evolution and uses of decision impact studies and their influence on the integration of emerging genomic technologies in cancer care. The results imply that DIS are positioned to provide evidence of clinical utility and impact clinical practice and reimbursement decision-making in cancer care. Systematic review registration: Open Science Framework osf.io/hm3jr.


Assuntos
Neoplasias da Mama , Masculino , Humanos , Prognóstico , Próstata , Genômica
7.
Semin Oncol Nurs ; 39(1): 151363, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36414522

RESUMO

OBJECTIVES: Nurses, as the largest healthcare workforce, are well-positioned to apply knowledge translation. The role of nursing leadership in facilitating evidence-based practice has been extensively discussed in the literature, but this is not the case for knowledge translation. The objective of this study was to examine the potential role of nurse leaders in applying knowledge translation across health settings. DATA SOURCES: We reviewed the existing literature for evidence-based practice as best practice in clinical care; examined how a complex systems approach to knowledge translation may extend beyond evidence-based practice, and considered nursing leadership approaches including transformational leadership. CONCLUSION: In this discursive article, we discuss the differences between evidence-based practice and knowledge translation, highlight the promise of transformational leadership in facilitating knowledge translation through a complex systems lens, and argue for the importance of nurse leaders in facilitating and supporting complex knowledge translation across healthcare settings. IMPLICATIONS FOR NURSING PRACTICE: Although future research is needed to test our ideas, we argue that the advanced conceptual understanding generated in this article should inform a roadmap toward a future in which nurse leaders initiate, participate and advocate for complex knowledge translation across healthcare settings.


Assuntos
Prática Clínica Baseada em Evidências , Liderança , Humanos
8.
J Bone Joint Surg Am ; 104(7): 649-658, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35167503

RESUMO

➤ Although the criteria of Kocher et al. were an important advancement in our ability to diagnose septic arthritis of the hip early, the changing microbial landscape and availability of advanced imaging have rendered it insufficient for contemporary clinical use.➤ Routine use of magnetic resonance imaging and recognition of disseminated disease have prompted the development of algorithms to predict concurrent osteoarticular infection in cases of septic arthritis and osteomyelitis that were previously assumed to be "isolated."➤ Recent research has attempted to stratify childhood bone and joint infection (BJI) by severity to guide treatment planning. This is valuable, as patients with multifocal disease, more virulent pathogens, and immunocompromise can have longer hospital stays and require multiple surgeries.➤ The increasing prevalence of clinical prediction algorithms in childhood BJI is not completely matched by quality in methodology. Clinicians need to be wary of adopting predictive algorithms prior to robust external validation.

9.
Med J Aust ; 216(6): 312-319, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35201615

RESUMO

INTRODUCTION: The Australian Technical Advisory Group on Immunisation and New Zealand Ministry of Health recommend all children aged ≥ 5 years receive either of the two mRNA COVID-19 vaccines: Comirnaty (Pfizer), available in both Australia and New Zealand, or Spikevax (Moderna), available in Australia only. Both vaccines are efficacious and safe in the general population, including children. Children and adolescents undergoing treatment for cancer and immunosuppressive therapy for non-malignant haematological conditions are particularly vulnerable, with an increased risk of severe or fatal COVID-19. There remains a paucity of data regarding the immune response to COVID-19 vaccines in immunosuppressed paediatric populations, with data suggestive of reduced immunogenicity of the vaccine in immunocompromised adults. RECOMMENDATIONS: Considering the safety profile of mRNA COVID-19 vaccines and the increased risk of severe COVID-19 in immunocompromised children and adolescents, COVID-19 vaccination is strongly recommended for this at-risk population. We provide a number of recommendations regarding COVID-19 vaccination in this population where immunosuppressive, chemotherapeutic and/or targeted biological agents are used. These include the timing of vaccination in patients undergoing active treatment, management of specific situations where vaccination is contraindicated or recommended under special precautions, and additional vaccination recommendations for severely immunocompromised patients. Finally, we stress the importance of upcoming clinical trials to identify the safest and most efficacious vaccination regimen for this population. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This consensus statement provides recommendations for COVID-19 vaccination in children and adolescents aged ≥ 5 years with cancer and immunocompromising non-malignant haematological conditions, based on evidence, national and international guidelines and expert opinion. ENDORSED BY: The Australian and New Zealand Children's Haematology/Oncology Group.


Assuntos
COVID-19 , Hematologia , Neoplasias , Adolescente , Austrália/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Criança , Pré-Escolar , Humanos , Neoplasias/terapia , Nova Zelândia/epidemiologia , Vacinação
10.
Chemphyschem ; 23(6): e202200011, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35099849

RESUMO

The effects on the C-I⋅⋅N halogen bond between iodobenzene and NH3 of placing various substituents on the phenyl ring are monitored by quantum calculations. Substituents R=N(CH3 )2 , NH2 , CH3 , OCH3 , COCH3 , Cl, F, COH, CN, and NO2 were each placed ortho, meta, and para to the I. The depth of the σ-hole on I is deepened as R becomes more electron-withdrawing which is reflected in a strengthening of the halogen bond, which varied between 3.3 and 5.5 kcal mol-1 . In most cases, the ortho placement yields the largest perturbation, followed by meta and then para, but this trend is not universal. Parallel to these substituent effects is a progressive lengthening of the covalent C-I bond. Formation of the halogen bond reduces the NMR chemical shielding of all three nuclei directly involved in the C-I⋅⋅N interaction. The deshielding of the electron donor N is most closely correlated with the strength of the bond, as is the coupling constant between I and N, so both have potential use as spectroscopic measures of halogen bond strength.


Assuntos
Halogênios , Iodobenzenos , Amônia , Benzeno , Elétrons , Halogênios/química
11.
Global Spine J ; 12(8): 1814-1820, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33601908

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Despite pyogenic spondylodiscitis potentially conferring significant morbidity, there is no consensus on optimal treatment. The Brighton Spondylodiscitis Score (BSDS) was developed to identify patients who would likely fail conservative management and therefore benefit from earlier surgical intervention. In this study, we attempt external validation of the BSDS. METHODS: We carried out a retrospective review of all patients treated at our institution, 2010-2016, for pyogenic spondylodiscitis. 91 met inclusion criteria and 40 progressed to require surgical intervention. The BSDS was calculated for each patient allowing stratification into low-, moderate- and high-risk groups. Calibration and discrimination was assessed with ROC curve analysis and calibration plot. RESULTS: Area under the curve (AUC) was 0.469 (0.22-0.71) in our external validation, compared with AUC 0.83 and 0.71 (CI 0.50-0.88) in the original study and test populations respectively. Only 60% of patients in the high-risk group required surgery, 50% in the moderate, and 38% of the low indicating poor calibration and predictive accuracy. Operative intervention was not higher overall in our cohort (44% vs. 32%, p = 0.14). We found greater rates of bacteraemia, more distal infection, and more advanced MRI findings in our cohort. The incidence of spondylodiscitis in our region is higher (4/100 000/year). CONCLUSION: We failed to externally validate the BSDS in our population which is likely a result of unique population characteristics and the inherently variable pathology associated with spondylodiscitis. Clinicians must be cautious in adopting treatment algorithms developed in other health care systems that may comprise significantly different patient and pathogen characteristics.

12.
J Clin Neurosci ; 95: 94-98, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34929659

RESUMO

OBJECTIVE: Use of BMP in the setting of infection remains controversial. We examined the safety and effectiveness of BMP in the surgical treatment of pyogenic spondylodiscitis and compared patients who have been treated with or without BMP during surgery. METHODS: 57 patients who have undergone surgery for pyogenic spondylodiscitis after presenting to a tertiary Spine referral institution between 2011 and 2020 were included. 18 underwent surgery alone without BMP and 39 underwent surgery with BMP. Outcomes were compared between the two groups, including re-operations, infection recurrences, BMP- related complications and radiological fusion. RESULTS: The cohort comprised 41 males (71.9%) with a mean age 63.7 +/- 13.3 years. Surgical indications include instability (n = 18), pain (n = 4), neurological deficit (n = 15) and sepsis or failure of non-operative management (n = 20). In the group who underwent surgery without BMP, there were two cases of re-operation for infection recurrence (11.1%) and three cases of cage subsidence; 80% achieved definitive and probable fusion. In the group who underwent surgery with BMP, there were three cases of re-operation for infection recurrence (7.7%), three cases of cage subsidence and one case of BMP- related radiculitis; 96.5% achieved definitive and probable fusion. CONCLUSIONS: The use of BMP in the surgical treatment of pyogenic spondylodiscitis did not confer an increased risk of infection recurrence, revision surgery or radiculitis. BMP can be a useful and safe adjunct in surgical intervention for pyogenic spondylodiscitis.


Assuntos
Discite , Fusão Vertebral , Idoso , Discite/diagnóstico por imagem , Discite/cirurgia , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
13.
Lancet Oncol ; 22(2): e68-e80, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33539755

RESUMO

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.


Assuntos
Sobreviventes de Câncer , Preservação da Fertilidade/ética , Guias como Assunto , Neoplasias/epidemiologia , Adolescente , Adulto , Criança , Progressão da Doença , Feminino , Preservação da Fertilidade/tendências , Humanos , Masculino , Neoplasias/complicações , Neoplasias/patologia , Neoplasias/terapia , Adulto Jovem
14.
J Heart Lung Transplant ; 39(9): 934-944, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32487471

RESUMO

BACKGROUND: Gastroesophageal reflux disease (GERD) is a risk factor for chronic lung allograft dysfunction. Bile acids-putative markers of gastric microaspiration-and inflammatory proteins in the bronchoalveolar lavage (BAL) have been associated with chronic lung allograft dysfunction, but their relationship with GERD remains unclear. Although GERD is thought to drive chronic microaspiration, the selection of patients for anti-reflux surgery lacks precision. This multicenter study aimed to test the association of BAL bile acids with GERD, lung inflammation, allograft function, and anti-reflux surgery. METHODS: We analyzed BAL obtained during the first post-transplant year from a retrospective cohort of patients with and without GERD, as well as BAL obtained before and after Nissen fundoplication anti-reflux surgery from a separate cohort. Levels of taurocholic acid (TCA), glycocholic acid, and cholic acid were measured using mass spectrometry. Protein markers of inflammation and injury were measured using multiplex assay and enzyme-linked immunosorbent assay. RESULTS: At 3 months after transplantation, TCA, IL-1ß, IL-12p70, and CCL5 were higher in the BAL of patients with GERD than in that of no-GERD controls. Elevated TCA and glycocholic acid were associated with concurrent acute lung allograft dysfunction and inflammatory proteins. The BAL obtained after anti-reflux surgery contained reduced TCA and inflammatory proteins compared with that obtained before anti-reflux surgery. CONCLUSIONS: Targeted monitoring of TCA and selected inflammatory proteins may be useful in lung transplant recipients with suspected reflux and microaspiration to support diagnosis and guide therapy. Patients with elevated biomarker levels may benefit most from anti-reflux surgery to reduce microaspiration and allograft inflammation.


Assuntos
Ácidos e Sais Biliares/metabolismo , Bronquiolite Obliterante/cirurgia , Líquido da Lavagem Broncoalveolar/química , Refluxo Gastroesofágico/complicações , Rejeição de Enxerto/metabolismo , Transplante de Pulmão , Transplantados , Adulto , Idoso , Biomarcadores/metabolismo , Bronquiolite Obliterante/complicações , Feminino , Seguimentos , Refluxo Gastroesofágico/metabolismo , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
15.
Clin Cancer Res ; 26(15): 3936-3946, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357963

RESUMO

PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.


Assuntos
Antineoplásicos/administração & dosagem , Proteínas Estimuladoras de Ligação a CCAAT/agonistas , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Oligorribonucleotídeos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Lipossomos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Nanopartículas/administração & dosagem , Estadiamento de Neoplasias , Oligorribonucleotídeos/efeitos adversos , Oligorribonucleotídeos/farmacocinética , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
16.
Cancer Epidemiol ; 55: 104-109, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29902672

RESUMO

AIM: To evaluate the completeness and accuracy of child cancer registration in New Zealand. METHODS: Registrations for children aged 0-14 diagnosed between 1/1/2010 and 31/12/2014 were obtained from the New Zealand Cancer Registry (NZCR) and the New Zealand Children's Cancer Registry (NZCCR). Six key data fields were matched using National Health Index numbers in order to identify and resolve registration discrepancies. Capture-recapture methods were used to assess the completeness of cancer registration. RESULTS: 794 unique cases were reported; 718 from the NZCR, 721 from the NZCCR and 643 from both registries. 27 invalid cancer registrations were identified, including 19 residents of the Pacific Islands who had travelled to New Zealand for treatment. The NZCCR provided 55 non-malignant central nervous system tumour and 16 Langerhans cell histiocytosis cases which were not registered by the NZCR. The NZCR alerted the NZCCR to 18 cases missed due to human error and 23 cases that had not been referred to the specialist paediatric oncology centres. 762 cases were verified as true incident cases, an incidence rate of 166.8 per million. Registration accuracy for six key data fields was 98.6%. According to their respective inclusion criteria case completeness was 99.3% for the NZCR and 94.4% for the NZCCR. For childhood malignancies covered by both registries, capture-recapture methods estimated case ascertainment at greater than 99.9%. CONCLUSION: With two national registries covering childhood cancers, New Zealand is uniquely positioned to undertake regular cooperative activities to ensure high quality data is available for research and patient care.


Assuntos
Confiabilidade dos Dados , Neoplasias/epidemiologia , Controle de Qualidade , Sistema de Registros/estatística & dados numéricos , Sistema de Registros/normas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Nova Zelândia/epidemiologia
17.
J Subst Abuse Treat ; 60: 1-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26549295

RESUMO

National efforts are underway to integrate medical care and behavioral health treatment. This special issue of the Journal of Substance Abuse Treatment presents 13 papers that examine the integration of substance use interventions and medical care. In this introduction, the guest editors first describe the need to examine the integration of substance use treatment into medical care settings. Next, an overview of the emerging field of implementation science and its applicability to substance use intervention integration is presented. Preview summaries of each of the articles included in this special issue are given. Articles include empirical studies of various integration models, study protocol papers that describe currently funded implementation research, and one review/commentary piece that discusses federal research priorities, integration support activities and remaining research gaps. These articles provide important information about how to guide future health system integration efforts to treat the millions of medical patients with substance use problems.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Atenção Primária à Saúde/organização & administração , Transtornos Relacionados ao Uso de Substâncias/terapia , Humanos
18.
J Consult Clin Psychol ; 83(1): 68-80, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25365779

RESUMO

OBJECTIVE: Little is known about what may distinguish effective and ineffective group interventions. Group motivational interviewing (MI) is a promising intervention for adolescent alcohol and other drug use; however, the mechanisms of change for group MI are unknown. One potential mechanism is change talk, which is client speech arguing for change. The present study describes the group process in adolescent group MI and effects of group-level change talk on individual alcohol and marijuana outcomes. METHOD: We analyzed 129 group session audio recordings from a randomized clinical trial of adolescent group MI. Sequential coding was performed with the Motivational Interviewing Skill Code (MISC) and the CASAA Application for Coding Treatment Interactions software application. Outcomes included past-month intentions, frequency, and consequences of alcohol and marijuana use; motivation to change; and positive expectancies. RESULTS: Sequential analysis indicated that facilitator open-ended questions and reflections of change talk increased group change talk. Group change talk was then followed by more change talk. Multilevel models accounting for rolling group enrollment revealed group change talk was associated with decreased alcohol intentions, alcohol use, and heavy drinking 3 months later; group sustain talk was associated with decreased motivation to change, increased intentions to use marijuana, and increased positive alcohol and marijuana expectancies. CONCLUSIONS: Facilitator speech and peer responses each had effects on change and sustain talk in the group setting, which were then associated with individual changes. Selective reflection of change talk in adolescent group MI is suggested as a strategy to manage group dynamics and increase behavioral change.


Assuntos
Comportamento do Adolescente/psicologia , Fumar Maconha/prevenção & controle , Entrevista Motivacional/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Psicoterapia de Grupo/métodos , Consumo de Álcool por Menores/prevenção & controle , Adolescente , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Addict Behav ; 39(6): 1081-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24656642

RESUMO

OBJECTIVE: Substance use and delinquency among adolescents have been shown to be positively associated; however, the temporal relationship is not well understood. Examining the association between delinquency and substance use is especially relevant among adolescents with a first-time substance use related offense as they are at-risk for future problems. METHOD: Data from 193 adolescents at time of diversion program entry and six months later was examined using cross-lagged path analysis to determine whether substance use and related consequences were associated with other types of delinquency across time. RESULTS: Results demonstrated that delinquency at program entry was related to subsequent reports of heavy drinking and alcohol consequences, but not marijuana use or its consequences. In contrast, alcohol and marijuana use at program entry were not related to future reports of delinquency. CONCLUSIONS: Findings emphasize the need to build in comprehensive assessments and interventions for youth with a first time offense in order to prevent further escalation of substance use and criminal behaviors.


Assuntos
Comportamento do Adolescente/psicologia , Delinquência Juvenil/psicologia , Delinquência Juvenil/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , California/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Fumar Maconha/epidemiologia , Fumar Maconha/psicologia , Tempo
20.
J Clin Oncol ; 31(2): 224-30, 2013 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-23213088

RESUMO

PURPOSE: Little is known about the influence of socioeconomic factors on patient access to cancer trials. Differences should be considered to ensure generalizability of trial results and equality of access. METHODS: Phase I trials unit referrals at our center over 5 years, from 2007 to 2012, were reviewed. Socioeconomic status was defined by the Index of Multiple Deprivation (IMD; 1, least deprived; 5, most deprived). Multivariate analysis was performed comparing incident cancer cases with referred patients and those ultimately enrolled onto a trial. RESULTS: Four hundred thirty patients were referred (median age, 62 years). Compared with 10,784 incident cases, referral was less likely for patients in the more-deprived quintiles compared with the least deprived (IMD 5: odds ratio [OR], 0.53; 95% CI, 0.38 to 0.74). Once reviewed in the unit, enrollment onto a trial was not affected (IMD 5: OR, 0.81; 95% CI, 0.40 to 1.63). Ethnicity analysis showed the nonwhite population was less likely to be recruited (OR, 0.48; 95% CI, 0.26 to 0.88). This relationship was lost with adjustment for age, sex, cancer type, and deprivation index. CONCLUSION: We show for the first time to our knowledge that socioeconomic status affects early-phase cancer trial referrals. The least-deprived patients are almost twice as likely to be referred compared with the most deprived. This may be because more-deprived patients are less suitable for a trial-as a result of comorbidities, for example-or because of inequalities that could be addressed by patient or referrer education. Once reviewed at the unit, enrollment onto a trial is not affected by deprivation.


Assuntos
Ensaios Clínicos como Assunto/economia , Ensaios Clínicos Fase I como Assunto/economia , Acessibilidade aos Serviços de Saúde/economia , Neoplasias/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/psicologia , Classe Social , Reino Unido/epidemiologia , Adulto Jovem
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