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1.
BMJ Open ; 14(1): e078399, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296271

RESUMO

INTRODUCTION: As cancer incidence continues to rise, challenges remain in how to communicate accurate, timely information to people with cancer, their families and healthcare professionals. One option is to provide support and comprehensive, tailored information via a telephone cancer information and support service (CISS). This systematic review aims to summarise the service characteristics of telephone CISS and identify what aspects of services are important from callers' perspectives. METHODS AND ANALYSIS: A comprehensive literature search will be conducted for articles published from database inception to 30 March 2023 (OVID MEDLINE, EMBASE, CINAHL, PsycINFO and SocINDEX). Published, peer-reviewed, articles reporting qualitative research on the service characteristics of telephone CISS important to callers in any language will be included. One researcher will complete the searches, two researchers will independently screen results for eligible studies and a third researcher will resolve any disagreement. A narrative and thematic synthesis of studies will be provided. Study characteristics will be independently extracted by one researcher and checked by a second. Included studies' methodological quality will be evaluated independently by two researchers using the 2022 Critical Appraisal Skills Programme Qualitative Studies Checklist. Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research tool will assess the confidence of the review findings. ETHICS AND DISSEMINATION: Ethics approval is not required for this research as it is a planned systematic review of published literature. Findings will be presented at leading cancer, health economic and supportive care conferences, published in a peer-reviewed journal, and disseminated via websites and social media. PROSPERO REGISTRATION NUMBER: CRD42023413897.


Assuntos
Pessoal de Saúde , Neoplasias , Humanos , Revisões Sistemáticas como Assunto , Pesquisa Qualitativa , Neoplasias/terapia , Telefone , Projetos de Pesquisa
2.
PLoS One ; 18(11): e0293724, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37934771

RESUMO

BACKGROUND: Caring for someone with cancer during end of life care can be a challenging and complex experience. Those living in rural and regional areas are less likely to have local healthcare services and may be physically isolated. Even where support services such as respite do exist, they may be less likely to be accessed due to the time burden in travelling to services. This was compounded by the COVID-19 pandemic. AIM: To understand the potential benefits of peer support for bereaved carers of people with cancer from rural and regional locations during the COVID-19 period. METHODS: Phone interviews were conducted with bereaved cancer carers living in rural and regional areas in Victoria. Semi-structured interviews were used, and participants were asked about their experience as a carer, bereavement and the potential for peer support. Interviews were audio recorded and transcribed verbatim; transcripts were coded and a thematic analysis was conducted. FINDINGS: 12 interviews were conducted. Carers were mostly female (85%) and were on average 58 years of age (range 42-71). Interviews lasted an average of 58 minutes (range 53-91 minutes). Three themes were derived from the data; 1) Supportive care needs while caring and the impact of COVID-19; 2) Isolation during bereavement compounded by the COVID-19 pandemic; and 3) Peer support requires flexibility to meet diverse needs. CONCLUSION: Peer support has potential to assist bereaved carers of people with cancer. A co-design approach may be beneficial for developing a flexible model for supporting and linking carers together.


Assuntos
COVID-19 , Neoplasias , Assistência Terminal , Humanos , Feminino , Masculino , Cuidadores , Pandemias , COVID-19/epidemiologia
3.
BMJ Open ; 11(10): e055026, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598994

RESUMO

OBJECTIVE: To gather preliminary qualitative data that will assist in the codesign and development of a new informational and supportive website to assist informal cancer carers in Australia. DESIGN AND SETTING: Utilising a previously tested codesign process, informal carers' experiences and perspectives, including those of healthcare professionals', were examined via focus groups and/or interviews. Data were analysed via thematic analysis. PARTICIPANTS: Rural (n=9) and urban (n=11) carers', and healthcare professionals' (n=8) perspectives were collected. Carers participated in a focus group (n=9) or telephone interview (n=11). Healthcare professionals completed an interview (n=6) or online survey (n=2). RESULTS: Rural and urban carers typically felt ill prepared for their multitudinal caregiving responsibilities. Supporting patient-to-healthcare professional liaisons could especially challenge. Carers' biopsychosocial and fiscal strains were affected by patients' hardships and available informal supports. Rural carers described greater social support than urban carers. Both rural and urban carers also described discontentment related to a carer neglecting healthcare system. Both carers and healthcare professionals endorsed the need for a user-friendly, carer-specific website encompassing practical information and resources, peer-driven advice and evidence-based illness information, tailored to the Australian context. CONCLUSIONS: Carers and healthcare professionals recognise the pressing need for an Australian, cancer carer-specific online resource. Findings will inform the next phase, where a resource will be designed, developed and tested.


Assuntos
Cuidadores , Neoplasias , Austrália , Atenção à Saúde , Humanos , Neoplasias/terapia , Pesquisa Qualitativa , Apoio Social
4.
Contraception ; 104(4): 420-425, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33894250

RESUMO

OBJECTIVE: To better understand medication abortion attitudes and interest in future provision among Internal Medicine primary care providers (IM PCPs), and to characterize barriers to provision. STUDY DESIGN: We conducted a survey with IM attendings and trainees at a large academic medical center in Western Pennsylvania. We used descriptive statistics to characterize attitudes towards medication abortion provision, including the belief that it is within their scope of practice and interest in future provision, and to explore perceived barriers to provision. We used logistic regression models to assess factors associated with each of these attitudes. RESULTS: Of 397 eligible attendings and trainees, 121 (30%) completed the survey. Among those surveyed, 44% believed medication abortion is within the scope of practice of IM PCPs with trainees and female-identifying providers being significantly more likely to believe medication abortion is within their scope of practice compared to attending physicians and male physicians (60% vs 30%, p < 0.01 and 53% vs 31%, p = 0.01, respectively). Similarly, 43% endorsed interest in future provision, with trainees (67% vs 23%, p < 0.001) and female providers (54% vs 27%, p = 0.002) being more likely to express interest. The most cited barriers to provision included limited training in residency (70%) and low familiarity with abortion medications (57%). CONCLUSIONS: Many IM providers- particularly trainees- believe medication abortion is within their scope of practice and would like to provide this care. Interventions are needed to provide education and assistance complying with state and federal regulations to enable safe and efficient medication abortion provision by IM providers. IMPLICATIONS: IM departments and residency programs should seek to ensure training is offered to clinicians interested in providing medication abortion as a part of their primary care practice.


Assuntos
Aborto Induzido , Atitude do Pessoal de Saúde , Médicos/psicologia , Direitos Sexuais e Reprodutivos , Feminino , Humanos , Medicina Interna , Masculino , Gravidez , Atenção Primária à Saúde , Inquéritos e Questionários , Saúde da Mulher
5.
BMC Cancer ; 20(1): 963, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023538

RESUMO

BACKGROUND: Healthy Living after Cancer (HLaC) was a national dissemination and implementation study of an evidence-based lifestyle intervention for cancer survivors. The program was imbedded into existing telephone cancer information and support services delivered by Australian state-based Cancer Councils (CC). We report here the reach, effectiveness, adoption, implementation, and maintenance of the program. METHODS: In this phase IV study (single-group, pre-post design) participants - survivors of any type of cancer, following treatment with curative intent - received up to 12 nurse/allied health professional-led telephone health coaching calls over 6 months. Intervention delivery was grounded in motivational interviewing, with emphasis on evidence-based behaviour change strategies. Using the RE-AIM evaluation framework, primary outcomes were reach, indicators of program adoption, implementation, costs and maintenance. Secondary (effectiveness) outcomes were participant-reported anthropometric, behavioural and psychosocial variables including: weight; physical activity; dietary intake; quality-of-life; treatment side-effects; distress; and fear of cancer recurrence and participant satisfaction. Changes were evaluated using linear mixed models, including terms for timepoint (0/6 months), strata (Cancer Council), and timepoint x strata. RESULTS: Four of 5 CCs approached participated in the study. In total, 1183 cancer survivors were referred (mostly via calls to the Cancer Council telephone information service). Of these, 90.4% were eligible and 88.7% (n = 791) of those eligible consented to participate. Retention rate was 63.4%. Participants were mostly female (88%), aged 57 years and were overweight (BMI = 28.8 ± 6.5 kg/m2). Improvements in all participant-reported outcomes (standardised effect sizes of 0.1 to 0.6) were observed (p < 0.001). The program delivery costs were on average AU$427 (US$296) per referred cancer survivor. CONCLUSIONS: This telephone-delivered lifestyle intervention, which was feasibly implemented by Cancer Councils, led to meaningful and statistically significant improvements in cancer survivors' health and quality-of-life at a relatively low cost. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12615000882527 (registered on 24/08/2015).


Assuntos
Estilo de Vida Saudável/fisiologia , Neoplasias/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
J Adolesc Health ; 66(5): 626-628, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32331625

RESUMO

PURPOSE: Sexually active adolescents are at risk for sexually transmitted infections (STIs), yet screening is infrequently performed during pediatric visits. Lack of parent support and confidentiality are barriers. We explored whether parents of 15- to 17-year-olds would accept chlamydia and gonorrhea screening for their adolescent during a pediatric visit and assessed parental views on the importance of sexual health services. METHODS: A survey of 168 parents of adolescents was conducted during an outpatient pediatric office visit in Western Pennsylvania. RESULTS: Most parents (63%) accept STI screening for their adolescent during a pediatric visit, and 73% think it is important that adolescents spend time alone with their provider. Parents ranked the importance of discussing sexual health as high as other preventive health topics. CONCLUSIONS: Given the burden of STIs among adolescents, pediatricians should use this information to facilitate STI screening during office visits, secure time alone with their patients, and offer sexual health counseling.


Assuntos
Infecções Sexualmente Transmissíveis , Adolescente , Humanos , Programas de Rastreamento , Visita a Consultório Médico , Pais , Pennsylvania , Comportamento Sexual , Infecções Sexualmente Transmissíveis/diagnóstico
7.
ISME J ; 14(6): 1547-1560, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32203118

RESUMO

Sediment-hosted CO2-rich aquifers deep below the Colorado Plateau (USA) contain a remarkable diversity of uncultivated microorganisms, including Candidate Phyla Radiation (CPR) bacteria that are putative symbionts unable to synthesize membrane lipids. The origin of organic carbon in these ecosystems is unknown and the source of CPR membrane lipids remains elusive. We collected cells from deep groundwater brought to the surface by eruptions of Crystal Geyser, sequenced the community, and analyzed the whole community lipidome over time. Characteristic stable carbon isotopic compositions of microbial lipids suggest that bacterial and archaeal CO2 fixation ongoing in the deep subsurface provides organic carbon for the complex communities that reside there. Coupled lipidomic-metagenomic analysis indicates that CPR bacteria lack complete lipid biosynthesis pathways but still possess regular lipid membranes. These lipids may therefore originate from other community members, which also adapt to high in situ pressure by increasing fatty acid unsaturation. An unusually high abundance of lysolipids attributed to CPR bacteria may represent an adaptation to membrane curvature stress induced by their small cell sizes. Our findings provide new insights into the carbon cycle in the deep subsurface and suggest the redistribution of lipids into putative symbionts within this community.


Assuntos
Dióxido de Carbono/metabolismo , Água Subterrânea/microbiologia , Archaea/genética , Processos Autotróficos , Bactérias/genética , Carbono/metabolismo , Ciclo do Carbono , Colorado , Ecossistema , Lipídeos/análise , Metagenoma , Filogenia
8.
Nature ; 578(7795): 425-431, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32051592

RESUMO

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems.


Assuntos
Bactérias/virologia , Bacteriófagos/classificação , Bacteriófagos/genética , Planeta Terra , Ecossistema , Genoma Viral/genética , Filogenia , Aminoacil-tRNA Sintetases/genética , Animais , Bactérias/genética , Bacteriófagos/isolamento & purificação , Bacteriófagos/metabolismo , Biodiversidade , Sistemas CRISPR-Cas/genética , Evolução Molecular , Regulação Bacteriana da Expressão Gênica , Regulação Viral da Expressão Gênica , Especificidade de Hospedeiro , Humanos , Lagos/virologia , Anotação de Sequência Molecular , Oceanos e Mares , Prófagos/genética , Biossíntese de Proteínas , RNA de Transferência/genética , Proteínas Ribossômicas/genética , Água do Mar/virologia , Microbiologia do Solo , Transcrição Gênica
9.
Nat Microbiol ; 4(8): 1356-1367, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31110364

RESUMO

Soil microbial activity drives the carbon and nitrogen cycles and is an important determinant of atmospheric trace gas turnover, yet most soils are dominated by microorganisms with unknown metabolic capacities. Even Acidobacteria, among the most abundant bacteria in soil, remain poorly characterized, and functions across groups such as Verrucomicrobia, Gemmatimonadetes, Chloroflexi and Rokubacteria are understudied. Here, we have resolved 60 metagenomic and 20 proteomic data sets from a Mediterranean grassland soil ecosystem and recovered 793 near-complete microbial genomes from 18 phyla, representing around one-third of all microorganisms detected. Importantly, this enabled extensive genomics-based metabolic predictions for these communities. Acidobacteria from multiple previously unstudied classes have genomes that encode large enzyme complements for complex carbohydrate degradation. Alternatively, most microorganisms encode carbohydrate esterases that strip readily accessible methyl and acetyl groups from polymers like pectin and xylan, forming methanol and acetate, the availability of which could explain the high prevalence of C1 metabolism and acetate utilization in genomes. Microorganism abundances among samples collected at three soil depths and under natural and amended rainfall regimes indicate statistically higher associations of inorganic nitrogen metabolism and carbon degradation in deep and shallow soils, respectively. This partitioning decreased in samples under extended spring rainfall, indicating that long-term climate alteration can affect both carbon and nitrogen cycling. Overall, by leveraging natural and experimental gradients with genome-resolved metabolic profiles, we link microorganisms lacking prior genomic characterization to specific roles in complex carbon, C1, nitrate and ammonia transformations, and constrain factors that impact their distributions in soil.


Assuntos
Bactérias/genética , Carbono/metabolismo , Genômica , Pradaria , Nitrogênio/metabolismo , Microbiologia do Solo , Solo/química , Bactérias/classificação , Bactérias/metabolismo , Biodiversidade , California , Ciclo do Carbono , Ecologia , Ecossistema , Metagenômica , Ciclo do Nitrogênio , Proteômica
10.
JMIR Res Protoc ; 8(5): e12473, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31099341

RESUMO

BACKGROUND: Structured distress management, comprised a 2-stage screening and referral model, can direct supportive care resources toward individuals who are most likely to benefit. This structured approach has yet to be trialed in Australian community-based services such as Cancer Council New South Wales (NSW) and Victoria Cancer Information and Support (CIS) 13 11 20 lines who care for a large community of cancer patients and caregivers. OBJECTIVE: The aim of this study was to evaluate the effectiveness of structured screening and referral in (1) increasing the proportion of distressed CIS callers who accept supportive care referrals and (2) reducing distress levels at 6-month follow-up. METHODS: In this stepped-wedge trial, Cancer Council NSW and Victoria CIS consultants are randomized to deliver structured care during inbound 13 11 20 calls in accordance with 3 intervention periods. Eligible callers are patients or caregivers who score 4 or more on the Distress Thermometer; NSW or Victorian residents; aged 18 years or older; and English proficient. Study data are collected via computer-assisted telephone interviews (CATIs) at 3- and 6-month follow-up and CIS record audit. CATIs include demographic and service use items and the General Health Questionnaire (GHQ-28) to assess distress. An economic analysis of the structured care model will be completed. RESULTS: The structured care model was developed by guideline review and identification of service characteristics to guide mapping decisions; place-card methodology; and clinical vignettes with think-aloud methodology to confirm referral appropriateness. The model includes an additional screening tool (Patient Health Questionnaire-4) and a referral model with 16-20 CIS services. Descriptive statistics will be used to assess referral uptake rates. Differences between GHQ-28 scores for structured and usual care callers will be tested using a generalized linear mixed model with fixed effects for intervention and each time period. The trial will recruit 1512 callers. The sample size will provide the study with approximately 80% power to detect a difference of 0.3 SD in the mean score of the GHQ-28 at an alpha level of .05 and assuming an intra-cluster correlation of .04. A random sample of recorded calls will be reviewed to assess intervention fidelity and contamination. To date, 1835 distressed callers have been invited to participate with 60.71% (1114/1835) enrolled in the study. A total of 692 participants have completed 6-month CATIs. Recruitment is anticipated to end in late 2019. CONCLUSIONS: This trial is among the first to rigorously test the outcomes of a community-based structured approach to distress management. The model is evidence-informed, practice-ready, and trialed in a real-world setting. The study outcomes will advance the understanding of distress management internationally for both patients and caregivers. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12617000352303; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372105&isReview=true (Archived by WebCite on http://www.webcitation.org/78AW0Ba09). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12473.

11.
Ophthalmic Plast Reconstr Surg ; 34(5): e149-e151, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29979269

RESUMO

A 72-year-old Caucasian woman who had recurrent sebaceous carcinoma of the right orbit with bilateral cervical lymph node involvement 24 months after orbital exenteration was treated with carboplatin (area under the curve of 5) and pembrolizumab (2 mg/kg) for 6 cycles, followed by maintenance pembrolizumab. She obtained a complete pathological remission and remains free of local, regional, and systemic disease at 15 months.


Assuntos
Adenocarcinoma Sebáceo/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias das Glândulas Sebáceas/tratamento farmacológico , Adenocarcinoma Sebáceo/cirurgia , Idoso , Feminino , Humanos , Quimioterapia de Indução/métodos , Quimioterapia de Manutenção/métodos , Neoplasias das Glândulas Sebáceas/cirurgia , Resultado do Tratamento
13.
Anesth Prog ; 64(1): 17-21, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28128664

RESUMO

Little is known about implications of temperament for children who receive nitrous oxide inhalation sedation (N2O/O2) for dental care. The aim of this study was to investigate whether child temperament is associated with success in N2O/O2. Child-caregiver dyads were enrolled from patients aged 36-95 months receiving dental care with N2O/O2 at a university-based pediatric dental clinic. To assess child temperament, 48 caregivers completed the Children's Behavior Questionnaire Short Form. Patient behavior was abstracted from Frankl scores recorded in the patient's chart. The overall behavioral failure rate was 15% (n = 7/48). There was no significant difference in sedation outcome associated with sex, health, insurance status, or complexity of treatment provided. Sedation outcome was significantly associated with the broad temperament domain of Effortful Control and its subscales Attentional Focusing and Inhibitory Control. The Negative Affectivity subscales of Frustration, Sadness, and Soothability and the Extraversion/Surgency subscales Activity and Impulsivity were also significantly associated with sedation outcome. The results of this study suggest that Effortful Control is associated with behavior during dental treatment with N2O/O2. The subscales of Attention Focusing, Inhibitory Control, Frustration, Fear, Sadness, Soothability, Activity, and Impulsivity may also be important determinants of child behavior during dental treatment.


Assuntos
Anestesia Dentária/métodos , Anestesia por Inalação/métodos , Anestésicos Inalatórios/administração & dosagem , Comportamento Infantil , Estado de Consciência/efeitos dos fármacos , Óxido Nitroso/administração & dosagem , Temperamento , Administração por Inalação , Fatores Etários , Criança , Pré-Escolar , Comportamento Cooperativo , Clínicas Odontológicas , Emoções , Feminino , Gases , Humanos , Masculino , Projetos Piloto , Inquéritos e Questionários , Washington
14.
Int J Radiat Oncol Biol Phys ; 95(5): 1513-1519, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27262359

RESUMO

PURPOSE: To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. METHODS AND MATERIALS: Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. The deviation of the results was used to inform future action levels. RESULTS: Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of ΔD of 0 ± 5 cGy or %ΔD of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (-2 ± 5 cGy) or summed field percentage dose difference (-6% ± 7%). CONCLUSIONS: The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups.


Assuntos
Neoplasias/diagnóstico , Neoplasias/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/instrumentação , Ecrans Intensificadores para Raios X , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
J Clin Invest ; 126(6): 2334-40, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27159395

RESUMO

Antibodies that target the immune checkpoint receptor programmed cell death protein 1 (PD-1) have resulted in prolonged and beneficial responses toward a variety of human cancers. However, anti-PD-1 therapy in some patients provides no benefit and/or results in adverse side effects. The factors that determine whether patients will be drug sensitive or resistant are not fully understood; therefore, genomic assessment of exceptional responders can provide important insight into patient response. Here, we identified a patient with endometrial cancer who had an exceptional response to the anti-PD-1 antibody pembrolizumab. Clinical grade targeted genomic profiling of a pretreatment tumor sample from this individual identified a mutation in DNA polymerase epsilon (POLE) that associated with an ultramutator phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that the presence of POLE mutation associates with high mutational burden and elevated expression of several immune checkpoint genes. Together, these data suggest that cancers harboring POLE mutations are good candidates for immune checkpoint inhibitor therapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , DNA Polimerase II/genética , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/terapia , Mutação , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/imunologia , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
16.
BMC Cancer ; 15: 992, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26690258

RESUMO

BACKGROUND: Given evidence shows physical activity, a healthful diet and weight management can improve cancer outcomes and reduce chronic disease risk, the major cancer organisations and health authorities have endorsed related guidelines for cancer survivors. Despite these, and a growing evidence base on effective lifestyle interventions, there is limited uptake into survivorship care. METHODS/DESIGN: Healthy Living after Cancer (HLaC) is a national dissemination and implementation study that will evaluate the integration of an evidence-based lifestyle intervention for cancer survivors into an existing telephone cancer information and support service delivered by Australian state-based Cancer Councils. Eligible participants (adults having completed cancer treatment with curative intent) will receive 12 health coaching calls over 6 months from Cancer Council nurses/allied health professionals targeting national guidelines for physical activity, healthy eating and weight control. Using the RE-AIM evaluation framework, primary outcomes are service-level indicators of program reach, adoption, implementation/costs and maintenance, with secondary (effectiveness) outcomes of patient-reported anthropometric, behavioural and psychosocial variables collected at pre- and post-program completion. The total participant accrual target across four participating Cancer Councils is 900 over 3 years. DISCUSSION: The national scope of the project and broad inclusion of cancer survivors, alongside evaluation of service-level indicators, associated costs and patient-reported outcomes, will provide the necessary practice-based evidence needed to inform future allocation of resources to support healthy living among cancer survivors. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR)--ACTRN12615000882527 (registered on 24/08/2015).


Assuntos
Promoção da Saúde/métodos , Estilo de Vida , Neoplasias/reabilitação , Adulto , Idoso , Austrália , Análise Custo-Benefício , Dieta , Exercício Físico , Feminino , Promoção da Saúde/economia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Projetos de Pesquisa , Apoio Social , Inquéritos e Questionários , Sobreviventes , Telefone , Adulto Jovem
17.
Pediatr Dent ; 37(5): 429-35, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26531085

RESUMO

PURPOSE: The purpose of this study was to investigate whether temperament, as measured by the Children's Behavior Questionnaire Short Form (CBQ-SF), was associated with success in oral sedation. METHODS: Child-caregiver dyads were enrolled from patients presenting for midazolam, meperidine, and hydroxyzine oral sedation. Children between 36 and 95 months of age, American Society of Anesthesiology (ASA) classification I or II, with diagnostic radiographs, whose parents believed he/she would swallow oral medications, were enrolled. To assess child temperament, caregivers completed the CBQ-SF. Behavior during sedation and overall sedation results were recorded using the Houpt Behavior Rating Scale. Failure was defined by Houpt overall ratings of fair or worse. The presence of disruptive behavior was also quantified. RESULTS: The sample population consisted of 61 patient-caregiver dyads. The overall sedation success rate was 87 percent (N equals 53). Disruptive behavior was present during 28 percent (N equals 17) of total cases. There was not a significant difference in failure rate or presence of disruptive behavior by age, sex, ASA status, insurance status, reason for sedation, or type of treatment provided. High impulsivity scores were significantly associated with disruptive behavior (P=.04). CONCLUSIONS: Impulsivity may be a determinant of a child's behavior during sedation.


Assuntos
Anestesia Dentária , Comportamento Infantil , Sedação Consciente , Comportamento Impulsivo , Temperamento , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Inquéritos e Questionários
18.
Am J Ophthalmol ; 158(4): 838-844.e1, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25036879

RESUMO

PURPOSE: To evaluate the clinical and immunopathologic features of 2 patients with bilateral dacryoadenitis associated with regional enteritis. DESIGN: Retrospective, clinicopathologic study. METHODS: Clinical records, photographs, and imaging studies were reviewed and microscopic sections of lacrimal gland biopsy samples were critically re-evaluated. The microscopic slides were stained with hematoxylin and eosin, special stains for organisms, and a range of immunohistochemical biomarkers, including CD3, CD4, CD5, CD8, CD20, CD68, CD138, CD1a, and immunoglobulins Ig G, IgG4, and IgA. RESULTS: Both patients were young women with a well-established diagnosis of regional enteritis. Histopathologic examination of biopsy samples disclosed moderate intraparenchymal fibrosis and lymphoplasmacytic infiltrates without lymphoid follicles. Small to medium intraparenchymal, noncaseating granulomas lacking multinucleated giant cells and, in 1 patient, CD68-positive and CD1a-negative palisading granulomas in widened interlobular fibrous septa were detected. Vasculitis and IgG4 plasma cells were not observed. Additional immunohistochemical studies revealed that CD8 T lymphocytes (suppressor or cytotoxic subset) predominated over CD4-positive T lymphocytes (helper cells) surrounding the necrobiotic foci and were intermixed with the CD68-positive histiocytes in the absence of CD20 B lymphocytes. Special stains for organisms demonstrated negative results. CONCLUSIONS: Dacryoadenitis is the rarest form of ocular adnexal involvement in regional enteritis, which affects the orbit far more frequently than ulcerative colitis. It is a granulomatous process with the possibility of palisading necrobiotic foci. In contrast, ulcerative colitis causes an interstitial lymphocytic and nongranulomatous myositis. Sarcoidosis, Wegener granulomatosis, and pseudorheumatoid nodules must be ruled out. Treatment options entail a wide variety of agents with selection based on empirical considerations and tailored to the patient's symptoms.


Assuntos
Doença de Crohn/complicações , Dacriocistite/etiologia , Doença Granulomatosa Crônica/etiologia , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Linfócitos T CD8-Positivos/imunologia , Doença de Crohn/diagnóstico , Dacriocistite/diagnóstico , Dacriocistite/tratamento farmacológico , Dacriocistite/cirurgia , Feminino , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/cirurgia , Humanos , Técnicas Imunoenzimáticas , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Sulfassalazina/uso terapêutico , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia
19.
J Pediatr Ophthalmol Strabismus ; 48 Online: e4-6, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21323306

RESUMO

Morning glory disc anomaly is a sporadic congenital abnormality of the optic disc that is often unilateral. These eyes possess heterotropic smooth muscle and can undergo spontaneous contraction with transient vision loss. The authors report an unusual case of contractility of a morning glory disc anomaly induced by ocular massage.


Assuntos
Contratura/etiologia , Músculo Liso/patologia , Disco Óptico/anormalidades , Doenças do Nervo Óptico/congênito , Blefaroptose/diagnóstico , Pré-Escolar , Contratura/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , Microftalmia/diagnóstico , Doenças do Nervo Óptico/diagnóstico , Acuidade Visual/fisiologia
20.
Ophthalmic Plast Reconstr Surg ; 27(5): e123-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21346674

RESUMO

A significant overlap of standard uptake values occurs in a variety of pathological processes, potentially causing misdiagnosis for tumor recurrence. The authors present a case of acute maxillary sinusitis masquerading as local recurrence of malignancy.


Assuntos
Neoplasias Oculares/diagnóstico por imagem , Sinusite Maxilar/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias de Bainha Neural/diagnóstico por imagem , Doença Aguda , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Tomografia por Emissão de Pósitrons , Complicações Pós-Operatórias/diagnóstico por imagem
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