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1.
Postgrad Med J ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38298001

RESUMO

PURPOSE: 'Low-value' clinical care and medical services are 'questionable' activities, being more likely to cause harm than good or with disproportionately low benefit relative to cost. This study examined the predictive ability of the QUestionable In Training Clinical Activities Index (QUIT-CAI) for general practice (GP) registrars' (trainees') performance in Australian GP Fellowship examinations (licensure/certification examinations for independent GP). METHODS: The study was nested in ReCEnT, an ongoing cohort study in which Australian GP registrars document their in-consultation clinical practice. Outcome factors in analyses were individual registrars' scores on the three Fellowship examinations ('AKT', 'KFP', and 'OSCE' examinations) and pass/fail rates during 2012-21. Analyses used univariable and multivariable regression (linear or logistic, as appropriate). The study factor in each analysis was 'QUIT-CAI score percentage'-the percentage of times a registrar performed a QUIT-CAI clinical activity when 'at risk' (i.e. when managing a problem where performing a QUIT-CAI activity was a plausible option). RESULTS: A total of 1265, 1145, and 553 registrars sat Applied Knowledge Test, Key Features Problem, and Objective Structured Clinical Exam examinations, respectively. On multivariable analysis, higher QUIT-CAI score percentages (more questionable activities) were significantly associated with poorer Applied Knowledge Test scores (P = .001), poorer Key Features Problem scores (P = .003), and poorer Objective Structured Clinical Exam scores (P = .005). QUIT-CAI score percentages predicted Royal Australian College of General Practitioner exam failure [odds ratio 1.06 (95% CI 1.00, 1.12) per 1% increase in QUIT-CAI, P = .043]. CONCLUSION: Performing questionable clinical activities predicted poorer performance in the summative Fellowship examinations, thereby validating these examinations as measures of actual clinical performance (by our measure of clinical performance, which is relevant for a licensure/certification examination).

2.
Int J Qual Health Care ; 35(4): 0, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37757860

RESUMO

Nonevidence-based and 'low-value' clinical care and medical services are 'questionable' clinical activities that are more likely to cause harm than good or whose benefit is disproportionately low compared with their cost. This study sought to establish general practitioner (GP), patient, practice, and in-consultation associations of an index of key nonevidence-based or low-value 'questionable' clinical practices. The study was nested in the Registrar Clinical Encounters in Training study-an ongoing (from 2010) cohort study in which Australian GP registrars (specialist GP trainees) record details of their in-consultation clinical and educational practice 6-monthly. The outcome factor in analyses, performed on Registrar Clinical Encounters in Training data from 2010 to 2020, was the score on the QUestionable In-Training Clinical Activities Index (QUIT-CAI), which incorporates recommendations of the Australian Choosing Wisely campaign. A cross-sectional analysis used negative binomial regression (with the model including an offset for the number of times the registrar was at risk of performing a questionable activity) to establish associations of QUIT-CAI scores. A total of 3206 individual registrars (response rate 89.9%) recorded 406 812 problems/diagnoses where they were at risk of performing a questionable activity. Of these problems/diagnoses, 15 560 (3.8%) involved questionable activities being performed. In multivariable analyses, higher QUIT-CAI scores (more questionable activities) were significantly associated with earlier registrar training terms: incidence rate ratios (IRRs) of 0.91 [95% confidence interval (CI) 0.87, 0.95] and 0.85 (95% CI 0.80, 0.90) for Term 2 and Term 3, respectively, compared to Term 1. Other significant associations of higher scores included the patient being new to the registrar (IRR 1.27; 95% CI 1.12, 1.45), the patient being of non-English-speaking background (IRR 1.24; 95% CI 1.04, 1.47), the practice being in a higher socioeconomic area decile (IRR 1.01; 95% CI 1.00, 1.02), small practice size (IRR 1.05; 95% CI 1.00, 1.10), shorter consultation duration (IRR 0.99 per minute; 95% CI 0.99, 1.00), and fewer problems addressed in the consultation (IRR 0.84; 95% CI 0.79, 0.89) for each additional problem]. Senior registrars' clinical practice entailed less 'questionable' clinical actions than junior registrars' practice. The association of lower QUIT-CAI scores with a measure of greater continuity of care (the patient not being new to the registrar) suggests that continuity should be supported and facilitated during GP training (and in established GPs' practice).


Assuntos
Medicina Geral , Clínicos Gerais , Cuidados de Baixo Valor , Humanos , Austrália , Estudos de Coortes , Estudos Transversais
3.
Aust J Gen Pract ; 52(7): 490-493, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37423247

RESUMO

BACKGROUND: The pace of new medical evidence is rapidly increasing. A modern doctor needs skills to access high-quality and up-to-date information to provide healthcare. Information seeking is often done at the point of care due to time constraints and because most consultations are conducted with the doctor and patient in the same space. There are benefits to accessing information during the consultation, and navigating this successfully requires skill. OBJECTIVE: Based on interviews with patients, this article aims to provide an updated practical approach for clinicians accessing reputable and reliable information with patients during consultations. DISCUSSION: Accessing information at the point of care is now an important clinical skill for clinicians; however, patients view this as a communication skill. Successful access and use of information can build trust through communication, transparency and actively involving the patient.


Assuntos
Comportamento de Busca de Informação , Médicos , Humanos , Encaminhamento e Consulta , Competência Clínica
4.
BMC Med Educ ; 22(1): 669, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36085053

RESUMO

BACKGROUND: Medical boards and healthcare providers internationally are coming under increasing pressure to attract international medical graduates (IMGs) and overseas trained doctors (OTDs) to cope with predicted general practice (GP) doctor shortages. Various pathways to registration are made available for this purpose. There is very little understanding of the effects of different training pathways to licensing and registration on the ability of IMGs and OTDs, as well as locally trained doctors, to acquire the desirable professional skills deemed necessary for working effectively in the primary care sector. METHODS: Feedback from patients was collected at the end of their scheduled consultation with their doctor using a questionnaire consisting of 13 Likert scale items that asked them to rate their experience of the consultation. Feedback was obtained for doctors going through the Royal Australian College of General Practice (RACGP) Practice Experience Program (PEP) and the Australian General Practice Training Program (AGPT), with the former intended primarily for IMGs and OTDs, and the latter for local medical graduates including from New Zealand. Patient feedback was also obtained for patients visiting already Fellowed and experienced GPs for comparative purposes, resulting in data for three groups of doctors (two trainee, one already Fellowed). Rater consistency and agreement measures, analysis of variance, principal component analysis, t-tests and psychometric network analysis were undertaken between and within groups to identify similarities and differences in patient experience and professionalism of doctors. RESULTS: There was a small but significant difference in average patient raw scores given to PEP and AGPT doctors (90.25, 90.97%), with the highest scores for 'Respect shown' (92.24, 93.15%) and the lowest for 'Reassurance' 89.38, 89.84%). Male patients gave lower scores (89.56%) than female patients (91.23%) for both groups of doctors. In comparison, patients gave experienced GPs an average 91.38% score, with male patients giving a lower average score than female patients (90.62, 91.93%). Two components were found in the patient data (interpersonal communication, caring/empathy) that account for over 80% of the variance. When patient scores were aggregated by doctor, the average PEP and AGPT doctor scores received were 90.27 and 90.99%, in comparison to the average experienced GP score of 91.43%. Network analysis revealed differences in the connectedness of items between these two groups as well as in comparison with experienced GPs, suggesting that PEP doctors' skills are less cohesively developed in the areas of listening ability, explaining and providing reassurance. CONCLUSIONS: The small but statistically significant differences between doctor groups reported in this preliminary study are supplemented by percentile analysis, network analysis and principal component analysis to identify areas for further exploration and study. There is scope for improving the integration of interpersonal communication skills of GPs in Training with their caring and empathy skills, when compared with experienced GPs as a benchmark. Suggestions are made for enhancing professional skills from a patients' perspective in future training programs.


Assuntos
Medicina Geral , Clínicos Gerais , Austrália , Escolaridade , Medicina de Família e Comunidade , Feminino , Humanos , Masculino
5.
BMJ Open ; 12(7): e061090, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35896298

RESUMO

OBJECTIVE: To explore patient perceptions regarding doctors' information seeking during consultations. DESIGN AND SETTING: Qualitative interviews with participants from six general practice waiting rooms in South East Queensland, Australia. Participants were asked about their experiences and opinions, and to comment on short videos of simulated consultations in which a doctor sought information. The interviews were analysed through a process of iterative thematic analysis using the framework of Braun and Clarke. PARTICIPANTS: The 16 participants were purposively sampled including 5 men and 11 women from a diverse range of educational and age groups. RESULTS: How a doctor's need to look up information impacted patient impressions of competence and trust was an overarching theme. The four dominant themes include: the trust a patient has in the doctor before the consultation, whether the doctor is expected to know the answer to a question without searching, has the doctor added value to the consultation by searching and the consultation skills used in the process. CONCLUSIONS: Patient trust is fundamental to positive perceptions of general practitioners' information seeking at the point-of-care. Communication is key to building this trust. Understanding the patient's agenda, listening, assessing thoroughly and being honest and transparent about the need to seek information all contribute to a positive experience.


Assuntos
Relações Médico-Paciente , Médicos , Feminino , Humanos , Comportamento de Busca de Informação , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Ferramenta de Busca
6.
BMC Med Educ ; 22(1): 494, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35751119

RESUMO

BACKGROUND: Multisource feedback is an evidence-based and validated tool used to provide clinicians, including those in training, feedback on their professional and interpersonal skills. Multisource feedback is mandatory for participants in the Royal Australian College of General Practitioners Practice Experience Program and for some Australian General Practice Training Registrars. Given the recency of the Practice Experience Program, there are currently no benchmarks available for comparison within the program and to other comparable cohorts including doctors in the Australian General Practice Training program. The aim of this study is to evaluate and compare colleague feedback within and across General Practice trainee cohorts. METHODS: Colleague feedback, from multisource feedback of Practice Experience Program participants and Australian General Practice Training Registrars, collected between January 2018 and April 2020, was compared to identify similarities and differences. Analyses entailed descriptive statistics, between and within groups rater consistency and agreement measures, principal component analysis, t-tests, analysis of variance, and psychometric network analysis. RESULTS: Colleague ratings of Practice Experience Program participants (overall average 88.58%) were lower than for Registrars (89.08%), although this difference was not significant. 'Communication with patients' was rated significantly lower for Practice Experience Program participants (2.13%) while this group was rated significantly better for their 'Ability to say no' (1.78%). Psychometric network analyses showed stronger linkages between items making up the behavioural component (compared to the items of the performance and self-management components, as found by principal component analysis) for Practice Experience Program participants as compared to Registrars. Practice Experience Program participants were stronger in clinical knowledge and skills as well as confidentiality, while Registrars were stronger in communicating with patients, managing their own stress, and in their management and leadership skills. CONCLUSIONS: The multisource feedback scores of doctors undertaking the Practice Experience Program suggests that, while all mean values are 'very good' to 'excellent', there are areas for improvement. The linkages between skills suggests that Practice Experience Program doctors' skills are somewhat isolated and have yet to fully synthesise. We now have a better understanding of how different groups of General Practitioners in training compare with respect to professional and interpersonal skills. Based on the demonstrated differences, the Practice Experience Program might benefit from the addition of educational activities to target the less developed skills.


Assuntos
Medicina Geral , Clínicos Gerais , Austrália , Retroalimentação , Humanos , Inquéritos e Questionários
7.
Br J Clin Pharmacol ; 88(8): 3803-3812, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35332558

RESUMO

AIMS: Neuromyelitis optica spectrum disorders (NMOSD) is an autoantibody-mediated, B cell-driven disease. Inebilizumab is a humanized, affinity-optimized, afucosylated IgG1 κ monoclonal antibody that binds to the B-cell specific surface antigen CD19, resulting in rapid, profound and sustained depletion of circulating peripheral B cells in NMOSD subjects (pivotal study). The objective of this study was to conduct population modelling of B-cell response following inebilizumab treatment in adult subjects with NMOSD, and to assess the impact of drug exposure to outcome. METHODS: A haematopoietic transit model was developed to describe the joint effects of reducing influx from pro-B cells and accelerating CD20+ B-cell depletion in the blood by inebilizumab. Furthermore, the relationships between inebilizumab pharmacokinetic (PK) exposure and the primary efficacy endpoint and key secondary efficacy endpoints were evaluated. RESULTS: At the 300-mg dose, there was no apparent relationship between efficacy (reduction in disease attack risk, risk of worsening from baseline in Expanded Disability Status Scale, cumulative total active MRI lesions, and the number of NMOSD-related in-patient hospitalizations) and PK exposure. Subjects with low, medium and high PK exposure had a similar hazard ratio of NMOSD attack vs. placebo group. CONCLUSION: The pharmacodynamic modelling confirmed effective depletion of B cells is achieved with a 300 mg intravenous dose of inebilizumab administered on Day 1 and Day 15 and every 6 months thereafter. The PK variability between patients had no apparent effect on clinical efficacy.


Assuntos
Neuromielite Óptica , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD19 , Antígenos CD20 , Humanos , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/patologia , Resultado do Tratamento
8.
Diabetes Res Clin Pract ; 166: 108290, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32615279

RESUMO

AIM: This study explores the General Practice (GP) experience of Gestational Diabetes Mellitus (GDM). Much has been written about patient perspectives, yet little is known about the GP perspective at initial diagnosis and management. GDM is increasingly managed in the secondary and tertiary sector, the confidence of GPs and their role in ongoing care has not been examined. Given GDM's poor follow up rates, all aspects of the patient journey warrant close examination. METHODS: Through purposive and snowball sampling, we conducted semi-structured interviews with GPs in Brisbane, Australia between April and October 2018. Data collection, until saturation, and analysis were concurrent, and the Leximancer analysis tool assisted with content analysis and suggestion of themes. RESULTS: Dominant themes include uncertainty/urgency and feeling under-utilised. GPs have a pragmatic approach in the face of uncertainty, and adopt one of several strategies to meet patient needs. A key issue that may impact on long term follow up and high quality GP-patient relationships is concern about the patient being 'taken away' by the hospital. Communication with the hospital is generally perceived as poor. CONCLUSIONS: The experience of GPs in the initial diagnosis and management of GDM may assist in improving GDM follow up.


Assuntos
Diabetes Gestacional/diagnóstico , Diabetes Gestacional/terapia , Clínicos Gerais , Padrões de Prática Médica , Atenção Primária à Saúde , Adulto , Austrália/epidemiologia , Continuidade da Assistência ao Paciente/normas , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Diabetes Gestacional/epidemiologia , Feminino , Seguimentos , Medicina Geral/normas , Medicina Geral/estatística & dados numéricos , Clínicos Gerais/normas , Clínicos Gerais/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Parto , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Gravidez , Cuidado Pré-Natal/normas , Cuidado Pré-Natal/estatística & dados numéricos , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/normas , Encaminhamento e Consulta/estatística & dados numéricos
9.
Women Birth ; 33(6): e492-e504, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31859253

RESUMO

The postpartum period is a time when physical, psychological and social changes occur. Health professional contact in the first month following birth may contribute to a smoother transition, help prevent and manage infant and maternal complications and reduce health systems' expenditure. The aim of this systematic review was to assess the effect of face-to-face health professional contact with postpartum women within the first four weeks following hospital discharge on maternal and infant health outcomes. Fifteen controlled trial reports that included 8332 women were retrieved after searching databases and reference lists of relevant trials and reviews. Although the evidence was of moderate or low quality and the effect size was small, this review suggests that at least one health professional contact within the first 4 weeks postpartum has the potential to reduce the number of women who stop breastfeeding within the first 4-6 weeks postpartum (Risk Ratio 0.86 (95% Confidence Interval 0.75-0.99)) and the number of women who cease exclusive breastfeeding by 4-6 weeks (Risk Ratio 0.84 (95% Confidence Interval 0.71-0.99)) and 6 months (Risk Ratio 0.88 (95% Confidence Interval 0.81-0.96). There was no evidence that one form of health professional contact was superior to any other. There was insufficient evidence to show that health professional contact in the first month postpartum, at a routine or universal level, had an impact on other aspects of maternal and infant health, including non-urgent or urgent use of health services.


Assuntos
Aleitamento Materno , Visita Domiciliar , Cuidado Pós-Natal/métodos , Feminino , Humanos , Recém-Nascido , Período Pós-Parto
10.
Aust J Gen Pract ; 47(6): 333-336, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29966182

RESUMO

BACKGROUND: Cochrane reviews are difficult to construct and may be difficult to read, but they produce trusted, high-quality research responses to common clinical questions. OBJECTIVE: The objective of this article is to help clinicians navigate the Cochrane Library and Cochrane reviews. Using a common clinical scenario, we illustrate how to find the information required to guide evidence-based decision making with patients. DISCUSSION: Clinicians looking for answers to clinical questions often turn first to guidelines. However, these may not provide enough background to balance the pros and cons of a treatment. Cochrane reviews often inform guidelines and contain more in-depth clinical information for shared decision making. The introduction of Summary of Findings (SoF) tables has made the studies in Cochrane reviews more accessible. In this paper, we discuss how to read and interpret these SoF tables. Additional resources, such as journal summaries and podcasts, have also improved the accessibility of Cochrane review findings.


Assuntos
Medicina Baseada em Evidências/métodos , Clínicos Gerais/educação , Publicações Periódicas como Assunto/tendências , Clínicos Gerais/normas , Humanos , Comportamento de Busca de Informação , Publicações Periódicas como Assunto/normas
11.
Med Educ ; 52(8): 786-788, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29992685
12.
Ann Intern Med ; 166(11): W57-W63, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28586898
13.
Cochrane Database Syst Rev ; (4): CD006821, 2015 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-25892369

RESUMO

BACKGROUND: Acute upper respiratory tract infections (URTIs), including the common cold and rhinosinusitis, are common afflictions that cause discomfort and debilitation and contribute significantly to workplace absenteeism. Treatment is generally by antipyretic and decongestant drugs and sometimes antibiotics, even though most infections are viral. Nasal irrigation with saline is often employed as an adjunct treatment for URTI symptoms despite a relative lack of evidence for benefit in this clinical setting. This review is an update of the Cochrane review by Kassel et al, which found that saline was probably effective in reducing the severity of some symptoms associated with acute URTIs. OBJECTIVES: To assess the effects of saline nasal irrigation for treating the symptoms of acute URTIs. SEARCH METHODS: We searched CENTRAL (2014, Issue 7), MEDLINE (1966 to July week 5, 2014), EMBASE (1974 to August 2014), CINAHL (1982 to August 2014), AMED (1985 to August 2014) and LILACS (1982 to August 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing topical nasal saline treatment to other interventions in adults and children with clinically diagnosed acute URTIs. DATA COLLECTION AND ANALYSIS: Two review authors (DK, BM) independently assessed trial quality with the Cochrane 'Risk of bias' tool and extracted data. We analysed all data using the Cochrane Review Manager software. Due to the large variability of outcome measures only a small number of outcomes could be pooled for statistical analysis. MAIN RESULTS: We identified five RCTs that randomised 544 children (three studies) and 205 adults (exclusively from two studies). They all compared saline irrigation to routine care or other nose sprays, rather than placebo. We included two new trials in this update, which did not contribute data of sufficient size or quality to materially change the original findings. Most trials were small and we judged them to be of low quality, contributing to an unclear risk of bias. Most outcome measures differed greatly between included studies and therefore could not be pooled. Most results showed no difference between nasal saline treatment and control. However, one larger trial, conducted with children, did show a significant reduction in nasal secretion score (mean difference (MD) -0.31, 95% confidence interval (CI) -0.48 to -0.14) and nasal breathing (obstruction) score (MD -0.33, 95% CI -0.47 to -0.19) in the saline group. However, a MD of -0.33 on a four-point symptom scale may have minimal clinical significance. The trial also showed a significant reduction in the use of decongestant medication by the saline group. Minor nasal discomfort and/or irritation was the only side effect reported by a minority of participants. AUTHORS' CONCLUSIONS: Nasal saline irrigation possibly has benefits for relieving the symptoms of acute URTIs. However, the included trials were generally too small and had a high risk of bias, reducing confidence in the evidence supporting this. Future trials should involve larger numbers of participants and report standardised and clinically meaningful outcome measures.


Assuntos
Lavagem Nasal/métodos , Infecções Respiratórias/terapia , Cloreto de Sódio/uso terapêutico , Doença Aguda , Adulto , Criança , Resfriado Comum/terapia , Humanos , Laringite/terapia , Lavagem Nasal/efeitos adversos , Faringite/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite/terapia , Sinusite/terapia , Cloreto de Sódio/efeitos adversos
14.
Clin Gastroenterol Hepatol ; 12(12): 2106-12.e1, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24929235

RESUMO

BACKGROUND & AIMS: A recent study compared the efficacy of tenofovir disoproxil fumarate (TDF) vs the combination of emtricitabine and TDF (FTC/TDF) in patients with lamivudine-resistant chronic hepatitis B who were treated for as long as 96 weeks. We report findings from resistance analyses conducted for this study. METHODS: Two hundred eighty patients with chronic hepatitis B virus (HBV) infection and lamivudine resistance (confirmed by INNO-LiPA Multi-DR) were randomly assigned (1:1) to groups treated with TDF or FTC/TDF. The HBV reverse transcriptase domain from the polymerase gene from all patients was sequenced at baseline and from 18 viremic patients at week 96 or early discontinuation. RESULTS: At screening for the efficacy study, 99% of patients were found to have lamivudine resistance. Prior exposure to entecavir or entecavir resistance was observed in 12% of patients, and 22% of patients had been previously exposed to adefovir; 1.8% were resistant to adefovir. Only 18 patients (6.4%) qualified for sequence analysis, including 1 patient who experienced virologic breakthrough and 17 with persistent viremia. Six of these patients did not have any sequence changes from baseline in HBV reverse transcriptase (33%), and sequence analysis could not be performed for 5 patients (28%). In 2 patients who qualified for phenotypic analysis (1 given TDF and 1 given FTC/TDF), no resistance to TDF was observed. Neither previous treatment exposure nor resistance to entecavir or adefovir affected viral kinetics. However, the mean baseline level of HBV DNA was significantly higher in viremic patients than in patients with viral suppression by week 96 (7.28 log10 IU/mL vs 5.62 log10 IU/mL; P = .0003). CONCLUSIONS: No resistance to TDF was detected through 96 weeks of treatment in patients with lamivudine-resistant chronic hepatitis B. Prior treatment or resistance to entecavir or adefovir did not affect viral kinetics through 96 weeks. No additional benefit was observed with the addition of emtricitabine vs TDF monotherapy. ClinicalTrial.gov number: NCT00737568.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Farmacorresistência Viral , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Antivirais/farmacologia , DNA Viral/química , DNA Viral/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Quimioterapia Combinada , Emtricitabina , Vírus da Hepatite B/enzimologia , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Lamivudina/farmacologia , Mutação Puntual , DNA Polimerase Dirigida por RNA/genética , Análise de Sequência de DNA , Tenofovir
15.
J Thorac Oncol ; 7(5): 856-65, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22722787

RESUMO

PURPOSE: XL647 is an oral small-molecule inhibitor of multiple receptor tyrosine kinases, including endothelial growth factor receptor (EGFR), vascular endothelial growth factor receptor 2, HER2 and Ephrin type-B receptor 4 (EphB4). We undertook an open-label, multi-institutional Phase II study to investigate the efficacy and safety of XL647 in treatment-naive non-small-cell lung cancer patients clinically enriched for the presence of EGFR mutations. METHODS: Eligibility included patients with advanced-stage treatment-naive lung adenocarcinoma with a known sensitizing mutation of EGFR or patients with at least one of the following criteria: being Asian, female, or having minimal or no smoking history. Two dosing schedules were evaluated; in the "intermittent 5 & 9 dosing" cohort, XL647 350 mg for 5 days every 14 days was given; and in the "daily dosing" cohort, XL647 300 mg daily for 28 days was administered. Tumor EGFR mutation status was determined on available tissue. The primary end point was confirmed objective response rate. RESULTS: Forty-one patients were treated on the intermittent 5 & 9 dosing- and 14 on the daily-dosing schedule. The majority of patients were eligible on the basis of smoking history. The response rate and progression-free survival for the two schedules combined were 20% and 5.3 months (90% confidence interval, 3.7-6.7), respectively. Thirty-eight patients (69%) had material available for mutation testing and 14 EGFR-sensitizing mutations were detected. The response rate and progression-free survival for EGFR-mutation-positive patients were 57% (8/14) and 9.3 months (90% confidence interval, 5.5-11.7). The toxicities were comparable between the two schedules; the most common adverse effects being diarrhea, nausea, and fatigue. CONCLUSIONS: XL647 administered on an intermittent or daily-dosing schedule demonstrated antitumor activity in patients with EGFR-activating mutations. The adverse-event profile was similar for the two dosing schedules.


Assuntos
Adenocarcinoma/tratamento farmacológico , Compostos Azabicíclicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Azabicíclicos/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Coortes , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Quinazolinas/farmacocinética , Taxa de Sobrevida , Distribuição Tecidual , Proteínas ras/genética
16.
J Thorac Oncol ; 7(1): 219-26, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22011666

RESUMO

INTRODUCTION: Although patients with non-small cell lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor (EGFR) activating mutations commonly experience significant regressions when treated with erlotinib or gefitinib, they uniformly develop resistance to these agents. The secondary EGFR T790M mutation is found in 50% of patients with acquired resistance. Herein, we studied XL647, an oral small molecule inhibitor of multiple receptor tyrosine kinases, including EGFR, VEGFR2, HER2, and EphB4, in NSCLC patients known or suspected of having tumors harboring T790M. METHODS: Eligible patients included those with relapsed or recurrent advanced NSCLC who progressed after ≥12 weeks of stable disease or response to erlotinib or gefitinib and/or those patients with a documented EGFR T790M. XL647 300 mg was administered once daily. The primary end point was objective response rate. Pretreatment plasma samples were collected for mutation testing of circulating tumor DNA. RESULTS: Forty-one patients were enrolled; 33 were evaluable for efficacy. One partial response was observed (response rate 3% and 90% confidence interval, 0% to 14%). Of patients whose tumors harbored T790M, 67% (8/12) had progression of disease as best response compared with 14% (3/21) of those without this mutation. Plasma samples from 40 patients were available for mutation testing, 14 (35%) of which were found to have EGFR mutations. CONCLUSIONS: The 3% response rate observed did not meet the prespecified threshold to recommend further study of XL647 in patients who develop acquired resistance to erlotinib or gefitinib. Patients with T790M had a significantly worse progression-free survival.


Assuntos
Compostos Azabicíclicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Azabicíclicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Progressão da Doença , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Cloridrato de Erlotinib , Feminino , Gefitinibe , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/efeitos adversos , Resultado do Tratamento
17.
Med Image Comput Comput Assist Interv ; 11(Pt 2): 543-50, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18982647

RESUMO

This paper describes the development and results of initial testing of a cooperative robot assistant for retinal microsurgery. In the cooperative control paradigm, the surgeon and the robot share control of a tool attached to the robot through a force sensor. The system senses forces exerted by the operator on the tool and uses this information in various control modes to provide smooth, tremor-free, precise positional control and force scaling. The robot manipulator is specifically designed with retinal microsurgery in mind, having high efficacy, flexibility and ergonomics while meeting the accuracy and safety requirements of microsurgery. We have tested this robot on a biological model and we report the results for reliably cannulating approximately 80 microm diameter veins (equivalent in size to human retinal veins). We also describe improvements to the robot and the experimental setup facilitating more advanced set of experiments.


Assuntos
Microcirurgia/instrumentação , Procedimentos Cirúrgicos Oftalmológicos/instrumentação , Retina/anatomia & histologia , Retina/cirurgia , Retinoscópios , Robótica/instrumentação , Cirurgia Assistida por Computador/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Microcirurgia/métodos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Interface Usuário-Computador
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