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1.
Clin Infect Dis ; 77(7): 976-986, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37235212

RESUMO

BACKGROUND: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. METHODS: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. RESULTS: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). CONCLUSIONS: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.


Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Infecções por HIV , Meningite , Humanos , HIV , Estudos Retrospectivos , Nova Zelândia/epidemiologia , Austrália/epidemiologia , Criptococose/diagnóstico , Criptococose/epidemiologia , Hospitais , Antígenos de Fungos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia
2.
Clin Orthop Relat Res ; 480(4): 748-758, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648466

RESUMO

BACKGROUND: Dedifferentiated chondrosarcoma is a chondrosarcoma subtype associated with high rates of recurrence and a poor prognosis. Others have proposed treatment of dedifferentiated chondrosarcoma using osteosarcoma protocols, including perioperative chemotherapy. However, the rarity of this condition poses difficulties in undertaking single- institution studies of sufficient sample size. QUESTION/PURPOSE: Is perioperative chemotherapy associated with improved overall survival in patients with dedifferentiated chondrosarcoma? METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) 1973 to 2016 database for patients with a diagnosis of dedifferentiated chondrosarcoma (n = 308). As dedifferentiated chondrosarcoma was only classified as a distinct entity in SEER starting in 2000, only patients treated in 2000 and later were included. We excluded from our analyses those patients with distant disease at diagnosis, a primary site of disease other than bone or joints, and those who did not receive cancer-directed surgery. These criteria yielded 185 dedifferentiated chondrosarcoma patients for inclusion. We used Kaplan-Meier analyses and Cox proportional hazards models to assess the association of clinical, demographic, and treatment characteristics on overall survival (OS). RESULTS: After controlling for confounding variables, including age, sex, tumor size, stage, grade, location, and radiation treatment status, and after adjusting for missing data, no overall survival benefit was associated with receipt of chemotherapy in patients with dedifferentiated chondrosarcoma (hazard ratio 0.75 [95% confidence interval 0.49 to 1.12]; p = 0.16). CONCLUSION: Chemotherapy treatment of dedifferentiated chondrosarcoma was not associated with improved OS. These results must be viewed cautiously, given the limited granularity of information on chemotherapy treatment, the concerns regarding chemotherapy misclassification in SEER data, and the small sample of patients with dedifferentiated chondrosarcoma, all of which limit the power to detect a difference. Our findings are nevertheless consistent with those of prior reports in which no benefit of chemotherapy could be detected. Lack of clear benefit from perioperative chemotherapy in dedifferentiated chondrosarcoma argues that it should be used only after careful consideration, and ideally in the context of a clinical trial. LEVEL OF EVIDENCE: Level III, therapeutic study.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Osteossarcoma , Neoplasias Ósseas/tratamento farmacológico , Condrossarcoma/diagnóstico , Condrossarcoma/tratamento farmacológico , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Estudos Retrospectivos , Programa de SEER
3.
Australas J Dermatol ; 60(1): 57-59, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30175424

RESUMO

Mycobacterium abscessus is a rapidly growing mycobacterium which is reportedly increasing in prevalence. Infection of the skin and soft tissue with M. abscessus is rare but typically associated with trauma. We present two cases of M. abscessus infection linked by penetration through wetsuits.


Assuntos
Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus , Dermatopatias Bacterianas/microbiologia , Ferimentos Penetrantes/complicações , Adulto , Feminino , Humanos , Injeções Intramusculares/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Roupa de Proteção , Dermatopatias Bacterianas/tratamento farmacológico , Úlcera Cutânea/microbiologia , Natação
4.
BMC Complement Altern Med ; 19(1): 374, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864327

RESUMO

BACKGROUND: The use of Complementary Medicines (CMs) has significantly increased in Australia over the last decade. This study attempts to determine the extent to which complementary and alternative medicines are recorded, ceased or initiated in the acute hospital setting and investigate which health professionals have a role in this process. METHODS: A cross-sectional study of inpatients was conducted at a major tertiary teaching hospital. Patient's medical records were examined to determine the rates of complementary medicine (CM) use and recording on medication charts and discharge prescriptions. Patient progress notes were audited to determine which health professionals were involved with the initiation or cessation of CMs during the inpatient stay. RESULTS: Three hundred and forty-one patients were included for analysis of which 44.3% (n = 151) participants were recorded as utilizing a CM. Patients were admitted on a mean of 2 (±1.4[Sd]; 0-9[range]) CMs and discharged on a mean of 1.7 CMs (±1.3[Sd]; 0-5[range]). 274 individual CMs were recorded on inpatient medication reconciliation forms with multivitamins, magnesium, fish oil and cholecalciferol recorded the most frequently. One hundred and fifty-eight changes to patient CM usage were recorded during the patient hospitalisation. One hundred and seven of these changes (68%) were not accounted for in the patient progress notes. CONCLUSION: Patients use of CM in this hospital setting do not reflect the national estimated usage. On the occasions that CM products are included in patient records, they are subsequently deprescribed following patient examination in hospital. It is currently unclear which health professionals have a role in this deprescribing process.


Assuntos
Terapias Complementares/estatística & dados numéricos , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Public Health Nutr ; 21(8): 1503-1514, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29352833

RESUMO

OBJECTIVE: Encouraging people to eat more seafood can offer a direct, cost-effective way of improving overall health outcomes. However, dietary recommendations to increase seafood consumption have been criticised following concern over the capacity of the seafood industry to meet increased demand, while maintaining sustainable fish stocks. The current research sought to investigate Australian accredited practising dietitians' (APD) and public health nutritionists' (PHN) views on seafood sustainability and their dietary recommendations, to identify ways to better align nutrition and sustainability goals. DESIGN: A self-administered online questionnaire exploring seafood consumption advice, perceptions of seafood sustainability and information sources of APD and PHN. Qualitative and quantitative data were collected via open and closed questions. Quantitative data were analysed with χ 2 tests and reported using descriptive statistics. Content analysis was used for qualitative data. SETTING: Australia. SUBJECTS: APD and PHN were targeted to participate; the sample includes respondents from urban and regional areas throughout Australia. RESULTS: Results indicate confusion around the concept of seafood sustainability and where to obtain information, which may limit health professionals' ability to recommend the best types of seafood to maximise health and sustainability outcomes. Respondents demonstrated limited understanding of seafood sustainability, with 7·5 % (n 6/80) satisfied with their level of understanding. CONCLUSIONS: Nutrition and sustainability goals can be better aligned by increasing awareness on seafood that is healthy and sustainable. For health professionals to confidently make recommendations, or identify trade-offs, more evidence-based information needs to be made accessible through forums such as dietetic organisations, industry groups and nutrition programmes.


Assuntos
Dieta , Política Nutricional , Alimentos Marinhos , Austrália , Estudos Transversais , Ecossistema , Ácidos Graxos Ômega-3 , Promoção da Saúde , Humanos , Alimentos Marinhos/normas , Alimentos Marinhos/estatística & dados numéricos , Inquéritos e Questionários
6.
Aust J Prim Health ; 24(3): 273-279, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735003

RESUMO

Global usage and expenditure on complementary medicines is increasing. Over 50% of consumers purchase these products from pharmacies and expect pharmacists to provide them with appropriate information regarding efficacy and safety of these products. Internationally, pharmacists have identified their lack of detailed knowledge of the efficacy and safety of these products as a barrier to recommending these products. Currently, little is known about the actual knowledge Australian pharmacists have of these products. This research seeks to determine Australian pharmacists' knowledge of the efficacy and safety of complementary medicines. An online survey was validated and distributed by three professional pharmacy bodies in Australia and online social media to survey Australian pharmacists' knowledge of a selection of complementary medicines that are defined as having therapeutic benefits as per the Australian Therapeutic Guidelines. In total, 535 complete surveys were returned and included in the final analysis. Surveys were predominantly completed by community pharmacists. The mean knowledge score obtained was 62%. There were no statistically significantly different results from pharmacists with a nutritional qualification. Australian pharmacists appear to have a basic knowledge of complementary medicines with a defined clinical effect. Specialised and targeted education focussing on relevant and efficacious complementary medicines with strong clinical evidence base is required.


Assuntos
Terapias Complementares , Conhecimentos, Atitudes e Prática em Saúde , Farmacêuticos , Austrália , Terapias Complementares/efeitos adversos , Humanos
7.
J Appl Clin Med Phys ; 18(6): 268-274, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28895282

RESUMO

Education in patient safety and quality of care is a requirement for radiation oncology residency programs according to accrediting agencies. However, recent surveys indicate that most programs lack a formal program to support this learning. The aim of this report was to address this gap and share experiences with a structured educational program on quality and safety designed specifically for medical physics therapy residencies. Five key topic areas were identified, drawn from published recommendations on safety and quality. A didactic component was developed, which includes an extensive reading list supported by a series of lectures. This was coupled with practice-based learning which includes one project, for example, failure modes and effect analysis exercise, and also continued participation in the departmental incident learning system including a root-cause analysis exercise. Performance was evaluated through quizzes, presentations, and reports. Over the period of 2014-2016, five medical physics residents successfully completed the program. Evaluations indicated that the residents had a positive experience. In addition to educating physics residents this program may be adapted for medical physics graduate programs or certificate programs, radiation oncology residencies, or as a self-directed educational project for practicing physicists. Future directions might include a system that coordinates between medical training centers such as a resident exchange program.


Assuntos
Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Física Médica/educação , Internato e Residência/normas , Segurança do Paciente/normas , Radioterapia (Especialidade)/educação , Avaliação Educacional , Humanos
8.
Public Health Nutr ; 19(4): 585-92, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26122985

RESUMO

OBJECTIVE: Despite the usefulness of quantitative research, qualitative research methodologies are equally needed to allow researchers to better understand the important social and environmental factors affecting food choice and eating habits. The present paper contributes insights from narrative inquiry, a well-established qualitative methodology, to a food-related doctoral research study. The connections between food shoppers and the producer, family, friends and others in the food system, between eaters and the earth, and how these connections affect people's meaning-making of food and pathways to food citizenship, were explored in the research. DESIGN: The research used narrative inquiry methodology and focus groups for data collection. SETTING: Five different food-ways in the Canberra region of Australia were selected for the present research; that is, community gardens, community-supported agriculture, farmers' markets, fresh food markets and supermarkets. SUBJECTS: Fifty-two people voluntarily attended eight focus groups with four to nine participants in each. RESULTS: From a practical perspective, the present paper offers a guide to the way in which narrative inquiry has been applied to one research project. The paper describes the application of narrative inquiry methodology, revealing the important place of narratives in generating new knowledge. The paper further outlines how phased narrative analysis can lead to a defensible and rigorous interpretive framework grounded in the data generated from people's stories and meaning-making. CONCLUSIONS: We argue that individual, social and system change will not be possible without further rigorous qualitative studies to inform and complement the empirical basis of public health nutrition practice.


Assuntos
Coleta de Dados/métodos , Dieta , Meio Ambiente , Narração , Ciências da Nutrição , Meio Social , Adulto , Idoso , Austrália , Comportamento de Escolha , Comércio , Comunicação , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Pública , Pesquisa Qualitativa , Projetos de Pesquisa , Pesquisadores , Características de Residência
9.
Appetite ; 105: 674-87, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27395411

RESUMO

Despite the ability of the globalised food system to deliver varied and plentiful food supplies to most in the developed world it also disconnects consumers from where, how and by whom food is grown, which discourages food citizenship. This paper uses an ecological framework to examine the individual, social, physical and macro-level environments that can positively or negatively influence peoples' engagement with food citizenship. This research used narrative inquiry methodology and purposive sampling to gather stories through focus group conversations. Fifty-two people voluntarily attended focus groups comprised of food procurers from one of five sources: community gardens, Community Supported Agriculture (CSA), farmers' markets, fresh food markets or supermarkets. A narrative was constructed for each of these groups of food procurers; their commonalities and particularities were illuminated through a final interpretive narrative. The findings showed that the community gardeners exhibited a range of personal characteristics that prioritised engagement with local food systems. The physical setting of the community garden enabled the gardeners to make connections to the earth and the people within their social networks. The CSA and farmers' market groups were cognisant of the implications of their food choices and usually proved to be food citizens, as they selected seasonal, local and ethically produced food from their farmer(s). The fresh food market shoppers were ambivalent towards organic and seasonal food and the market setting did not connect them directly to the provenance of their food. The supermarket shoppers' disconnection from those who grew their food and where it was grown disempowered them from making sustainable food choices. Adjustments to the macro-level food environment are needed to enable people to have a greater commitment to food citizenship.


Assuntos
Comportamento do Consumidor , Preferências Alimentares/psicologia , Abastecimento de Alimentos , Meio Social , Adulto , Idoso , Comportamento de Escolha , Produtos Agrícolas , Dieta/psicologia , Fazendeiros , Feminino , Grupos Focais , Alimentos Orgânicos , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Narração , Pesquisa Qualitativa , Fatores Socioeconômicos
10.
Appetite ; 105: 218-31, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27181200

RESUMO

Although the globalised food system delivers unparalleled food variety and quantity to most in the developed world it also disconnects consumers from where, how and by whom food is grown. This change in the food system has resulted in an acceptance of an anonymous and homogeneous food supply, which has contributed to over-consumption and the rise in diet-related diseases. 'Nutritionism' responds to this issue by maintaining that a 'healthy diet' can be achieved by consuming the correct balance of energy and nutrients, but with limited success. Yet, some food cultures can moderate the effects of the environmental drivers of increasing global obesity rates. This paper draws on this premise and presents an alternative eco-dietetic response, exploring people's meaning-making of food and food culture through local food networks. This research used narrative inquiry methodology and purposive sampling to gather stories through focus group conversations. Twenty people attended focus groups comprised of food procurers from one of three local food networks in the Canberra region: community gardens, a modified Community Supported Agriculture (CSA) and farmers' markets. The findings showed that those using local food networks enjoyed a 'contemporary relational food culture' that highlighted the importance of people, place and time, in their visceral experiences of food. The community gardeners made meaning of food through their connections to the earth and to others. The farmers' market and CSA food procurers valued the seasonal, local and ethical food produced by their beloved farmer(s). This paper provides qualitative evidence that local food networks enable people to enjoy multi-dimensional relationships to food. Further research is required to examine whether experiencing a contemporary relational food culture can lead to improved health outcomes for people and the planet.


Assuntos
Comportamento do Consumidor , Dieta Saudável , Preferências Alimentares , Abastecimento de Alimentos , Alimentos Orgânicos , Modelos Psicológicos , Cooperação do Paciente , Agricultura/economia , Agricultura/ética , Território da Capital Australiana , Comportamento do Consumidor/economia , Dieta Saudável/economia , Dieta Saudável/ética , Dieta Saudável/etnologia , Dieta Saudável/psicologia , Fazendeiros , Feminino , Grupos Focais , Preferências Alimentares/ética , Preferências Alimentares/etnologia , Preferências Alimentares/psicologia , Abastecimento de Alimentos/economia , Abastecimento de Alimentos/ética , Alimentos Orgânicos/economia , Jardinagem/economia , Jardinagem/ética , Humanos , Internacionalidade , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Agricultura Orgânica/economia , Agricultura Orgânica/ética , Cooperação do Paciente/etnologia , Cooperação do Paciente/psicologia , Prazer , Pesquisa Qualitativa , Estações do Ano , Recursos Humanos
15.
Ann Surg Oncol ; 21(7): 2150-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24615180

RESUMO

PURPOSE: Retroperitoneal sarcomas (RPS) are rare malignancies, comprising just 10-15 % of all soft-tissue sarcomas. These are challenging tumors to treat, with surgical resection being the only modality capable of providing a cure. This study analyzed the management and survival of patients resected at a large academic institution. METHODS: A retrospective study of all patients with primary localized RPS referred to the University of Washington between January 2000 and January 2013 was performed. Univariate and multivariate Cox regression models were used to analyze progression-free survival (PFS) and overall survival (OS) by patient, tumor, and treatment variables. RESULTS: The study identified 132 patients. Median follow-up was 31.8 months. Median PFS was 33 months, and median OS was 111 months. Sixty patients (45.5 %) underwent a margin-negative resection (R0), 59 (44.7 %) had a microscopic margin-positive resection (R1), and 7 (5.3 %) had a macroscopic margin-positive resection (R2). Forty (30.3 %) patients received preoperative radiation, 28 (21.2 %) received neoadjuvant chemotherapy, and 7 (5.3 %) received both. Tumor grade and microscopic margin status emerged as statistically significant predictors for both PFS and OS. Tumor size was also found to correlate with PFS. No significant difference in OS or PFS was observed for histologic subtype, neoadjuvant chemotherapy, or neoadjuvant radiation. CONCLUSIONS: Complete surgical resection should remain the mainstay of management for RPS, with emphasis on achieving negative microscopic margins. Neither neoadjuvant chemotherapy nor radiation was shown to significantly improve survival, and their unclear role in the management of RPS requires evaluation in a prospective setting.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Retroperitoneais/cirurgia , Sarcoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias Retroperitoneais/mortalidade , Neoplasias Retroperitoneais/patologia , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/secundário , Taxa de Sobrevida
16.
J Contin Educ Health Prof ; 44(1): 53-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37079386

RESUMO

ABSTRACT: Continuing professional development (CPD) fosters lifelong learning and enables health care providers to keep their knowledge and skills current with rapidly evolving health care practices. Instructional methods promoting critical thinking and decision making contribute to effective CPD interventions. The delivery methods influence the uptake of content and the resulting changes in knowledge, skills, attitudes, and behavior. Educational approaches are needed to ensure that CPD meets the changing needs of health care providers. This article examines the development approach and key recommendations embedded in a CE Educator's toolkit created to evolve CPD practice and foster a learning experience that promotes self-awareness, self-reflection, competency, and behavioral change. The Knowledge-to-Action framework was used in designing the toolkit. The toolkit highlighted three intervention formats: facilitation of small group learning, case-based learning, and reflective learning. Strategies and guidelines to promote active learning principles in CPD activities within different modalities and learning contexts were included. The goal of the toolkit is to assist CPD providers to design educational activities that optimally support health care providers' self-reflection and knowledge translation into their clinical environment and contribute to practice improvement, thus achieving the outcomes of the quintuple aim.


Assuntos
Educação Continuada , Pessoal de Saúde , Humanos , Conhecimento , Aprendizagem Baseada em Problemas , Prática Profissional
17.
Trials ; 24(1): 133, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36814314

RESUMO

BACKGROUND: Healthcare-associated infections (HAIs) are a common, costly, yet largely preventable complication impacting patients in healthcare settings globally. Improving routine cleaning and disinfection of the hospital environment has been shown to reduce the risk of HAI. Contaminated shared medical equipment presents a primary transmission route for infectious pathogens, yet is rarely studied. The CLEEN study will assess how enhanced cleaning and disinfection of shared medical equipment affects the rate of HAIs in a tertiary hospital setting. The initiative is an evidence-based approach combining staff training, auditing and feedback to environmental services staff to enhance cleaning and disinfection practices. METHODS: The CLEEN study will use a stepped wedge randomised controlled design in 10 wards of one large Australian hospital over 36 weeks. The intervention will consist of 3 additional hours per weekday for the dedicated cleaning and disinfection of shared medical equipment on each ward. The primary outcome is to demonstrate the effectiveness of improving the quality and frequency of cleaning shared medical equipment in reducing HAIs, as measured by a HAI point prevalence study (PPS). The secondary outcomes include the thoroughness of equipment cleaning assessed using fluorescent marker technology and the cost-effectiveness of the intervention. DISCUSSION: Evidence from the CLEEN study will contribute to future policy and practice guidelines about the cleaning and disinfection of shared medical equipment. It will be used by healthcare leaders and clinicians to inform decision-making and implementation of best-practice infection prevention strategies to reduce HAIs in healthcare facilities. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12622001143718.


Assuntos
Infecção Hospitalar , Desinfecção , Humanos , Austrália/epidemiologia , Infecção Hospitalar/prevenção & controle , Centros de Atenção Terciária , Atenção à Saúde
18.
JAMA Oncol ; 9(12): 1660-1668, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37824131

RESUMO

Importance: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts. Objective: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions. Design, Setting, and Participants: This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis was performed from August 2016 to September 2022. Interventions: Two doses of IT GLA-SE (5 µg and 10 µg for 8 weekly doses) were tested for safety in combination with concurrent radiotherapy of the injected lesion. Main Outcomes and Measures: Primary end points were safety and tolerability. Secondary and exploratory end points included local response rates as well as measurement of antitumor immunity with immunohistochemistry and T-cell receptor (TCR) sequencing of tumor-infiltrating and circulating lymphocytes. Results: Twelve patients (median [range] age, 65 [34-78] years; 8 [67%] female) were treated across the 2 dose cohorts. Intratumoral GLA-SE was well tolerated, with only 1 patient (8%) experiencing a grade 2 adverse event. All patients achieved local control of the injected lesion after 8 doses, with 1 patient having complete regression (mean regression, -25%; range, -100% to 4%). In patients with durable local response, there were detectable increases in tumor-infiltrating lymphocytes. In 1 patient (target lesion -39% at 259 days of follow-up), TCR sequencing revealed expansion of preexisting and de novo clonotypes, with convergence of numerous rearrangements coding for the same binding sequence (suggestive of clonal convergence to antitumor targets). Single-cell sequencing identified these same expanded TCR clones in peripheral blood after treatment; these T cells had markedly enhanced Tbet expression, suggesting TH1 phenotype. Conclusions and Relevance: In this nonrandomized controlled trial, IT GLA-SE with concurrent radiotherapy was well tolerated and provided more durable local control than radiotherapy alone. Patients with durable local response demonstrated enhanced IT T-cell clonal expansion, with matched expansion of these clonotypes in the circulation. Additional studies evaluating synergism of IT GLA-SE and radiotherapy with systemic immune modulation are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02180698.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Feminino , Idoso , Masculino , Receptor 4 Toll-Like/agonistas , Linfócitos T , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/radioterapia , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia , Receptores de Antígenos de Linfócitos T
19.
Public Health Nutr ; 15(2): 268-76, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21733281

RESUMO

The current, globalised food system supplies 'cheap' food to a large proportion of the world's population, but with significant social, environmental and health costs that are poorly understood. The present paper examines the nature and extent of these costs for both rural and urban communities, by illustrating the financial pressures on food producers and manufacturers to produce cheap food, the disconnection people experience with how and where their food is produced, and the rise in obesity levels that plague the globe. The paper then proposes that community food systems may play an important role in mitigating the adverse environmental, economic and social effects of the dominant food system, by the use of more sustainable food production methods, the development of local economies and enabling closer connections between farmers and consumers. There are many opportunities for public health nutritionists to contribute to the local food system literature to ascertain whether these systems improve inequities, provide better access to healthy food and help stem the tide of rising global obesity levels. Public health nutritionists can play a key role in supporting people to become food citizens and to advocate for democratic and sustainable food systems.


Assuntos
Agricultura , Meio Ambiente , Abastecimento de Alimentos/estatística & dados numéricos , Alimentos/economia , Saúde Pública/economia , Agricultura/economia , Agricultura/métodos , Conservação dos Recursos Naturais , Custos e Análise de Custo , Saúde Ambiental , Monitoramento Ambiental , Monitoramento Epidemiológico , Abastecimento de Alimentos/economia , Humanos , Fome , Internacionalidade , Obesidade/epidemiologia , Obesidade/prevenção & controle , Vigilância da População
20.
Clin Cancer Res ; 28(8): 1701-1711, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-35115306

RESUMO

PURPOSE: To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design. EXPERIMENTAL DESIGN: Paired pre- and postneoadjuvant therapy specimens were retrospectively identified for 32 patients with STSs and analyzed by three modalities: multiplexed IHC, NanoString, and RNA sequencing with ImmunoPrism analysis. RESULTS: All 32 patients, representing a variety of STS histologic subtypes, received neoadjuvant radiotherapy and 21 (66%) received chemotherapy prior to radiotherapy. The most prevalent immune cells in the tumor before neoadjuvant therapy were myeloid cells (45% of all immune cells) and B cells (37%), with T (13%) and natural killer (NK) cells (5%) also present. Neoadjuvant therapy significantly increased the total immune cells infiltrating the tumors across all histologic subtypes for patients receiving neoadjuvant radiotherapy with or without chemotherapy. An increase in the percentage of monocytes and macrophages, particularly M2 macrophages, B cells, and CD4+ T cells was observed postneoadjuvant therapy. Upregulation of genes and cytokines associated with antigen presentation was also observed, and a favorable pathologic response (≥90% necrosis postneoadjuvant therapy) was associated with an increase in monocytic infiltrate. Upregulation of the T-cell checkpoint TIM3 and downregulation of OX40 were observed posttreatment. CONCLUSIONS: Standard neoadjuvant therapy induces both immunostimulatory and immunosuppressive effects within a complex sarcoma microenvironment dominated by myeloid and B cells. This work informs ongoing efforts to incorporate immune checkpoint inhibitors and novel immunotherapies into the neoadjuvant setting for STSs.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Imunidade , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma/terapia , Microambiente Tumoral
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