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PURPOSE: Breast cancer survivors following disease-modifying treatment frequently experience multiple-concurrent symptoms (Jansana et al. in Int J Cancer 149(10):1755 1767, 2021), negatively impacting their quality of life and increasing the risk of polypharmacy (Alwhaibi et al. in J Oncol Pharm Pract 26(5):1052 1059, 2020). This study evaluates the feasibility and acceptability of acupuncture for the management of the pain-fatigue-sleep disturbance-numbness/tingling symptom cluster in breast cancer survivors, and investigates relationships between the symptom cluster and Traditional Chinese Medicine (TCM) syndrome diagnosis. METHODS: This was a single-arm, pre-test/post-test feasibility trial conducted at Chris O'Brien Lifehouse Hospital, Australia. Breast cancer survivors who completed treatment and experienced clinically significant levels of two or more symptoms (pain, fatigue, sleep disturbance, numbness/tingling) were eligible to participate in the individualized, pragmatic 6-week acupuncture intervention. The primary outcome was feasibility and acceptability. Effectiveness was explored using a symptom cluster mean score. RESULTS: Twenty women enrolled in the study over an 11-week period and 90% completed the study. Most women agreed or completely agreed that acupuncture was feasible (85%), acceptable (90%), and appropriate (90%). Both mean and composite symptom cluster scores were significantly reduced (p < 0.001), as were individual symptom scores in fatigue (p < 0.001), sleep disturbance (p = 0.04), and numbness/tingling (p = 0.01). TCM syndromes most closely associated with this symptom cluster were Spleen qi deficiency and Heart fire. No adverse events were reported. CONCLUSION: This study demonstrated that acupuncture was safe and feasible, justifying a powered randomized control trial. Preliminary findings suggest beneficial effects of acupuncture for the management of the pain-fatigue-sleep disturbance-numbness/tingling symptom cluster for women with breast cancer. TCM syndromes identified in this trial may be used to guide acupuncture treatment protocols. CLINICAL TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000590763) on 21 April 2022.
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Terapia por Acupuntura , Neoplasias da Mama , Sobreviventes de Câncer , Fadiga , Estudos de Viabilidade , Transtornos do Sono-Vigília , Humanos , Feminino , Neoplasias da Mama/complicações , Pessoa de Meia-Idade , Terapia por Acupuntura/métodos , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia , Fadiga/etiologia , Fadiga/terapia , Adulto , Idoso , Austrália , Qualidade de Vida , Medicina Tradicional Chinesa/métodos , Manejo da Dor/métodosRESUMO
PURPOSE: The management of pain following cancer-related surgeries involves the use of opioid analgesics. Nevertheless, there is little evidence characterizing the utility and prescription patterns of opioids after these procedures. Our primary aim was to identify patients from three types of cancer surgery who were overprescribed with opioids. The secondary aim was to determine the potential predictors of overprescribing in the same period. METHODS: We conducted the study at a single cancer referral hospital. Opioid-naïve patients with breast, gynecologic, or head and neck cancer were studied. Patients were considered opioid-naïve if they had a history of opioid use ≤ 30 mg oral morphine equivalent daily dose for less than seven days in the preceding three months before surgery. We recruited eligible participants by convenience sampling on the wards until at least 102 patients were included in the final analysis. After discharge, we followed up on the participants on day 7 via telephone using a structured proforma including questions to identify the last date and amount of opioid dose taken. The equivalent days of opioid use were calculated by their 24-hr use before discharge and the number of doses prescribed for discharge. Our primary outcome was the prevalence of overprescribing in the three surgical specialties defined as the number of patients taking less than 50% of discharge opioids within the first seven days after discharge. We examined the predictors on incidents of overprescribing using multivariable Poisson regression as the secondary outcome. RESULTS: We recruited 119 patients, and 107 patients were included in the final analysis. There were 59/107 (55%) patients found to be overprescribed with opioids. At discharge, they exhibited lower mean numerical rating scale pain scores, lower mean pain severity scores, higher equivalent days of opioids prescribed, and not used opioids in the last 24 hr before discharge. The incidence of overprescribing was 2.4 times greater for patients prescribed with opioids without 24-hr opioid use (relative risk [RR], 2.38; 95% confidence interval [CI], 1.30 to 4.35; P = 0.005). Similarly, the incidence of overprescribing was 1.7 times greater for patients who had opioids 24 hr before discharge and were supplied with opioids for five equivalent days or more at the time of discharge (RR, 1.67; 95% CI, 1.09 to 2.56; P = 0.02). CONCLUSION: Our study shows that the majority of recruited patients undergoing breast, gynecologic, or head and neck cancer surgery were overprescribed opioids. Individualized assessments on patients' 24-hr opioid requirements before discharge and supplying for less than five days are important considerations to reduce overprescribing in opioid-naïve patients after cancer surgery.
RéSUMé: OBJECTIF: La prise en charge de la douleur à la suite d'interventions chirurgicales liées au cancer passe par l'utilisation d'analgésiques opioïdes. Néanmoins, il existe peu de données probantes caractérisant l'utilité et les habitudes de prescription des opioïdes après ces interventions. Notre objectif principal était d'identifier les patient·es de trois types de chirurgie du cancer auxquel·les des opioïdes avaient été surprescrits. L'objectif secondaire était de déterminer les prédicteurs potentiels de surprescription au cours de la même période. MéTHODE: Nous avons mené cette étude dans un seul hôpital de référence pour le cancer. La patientèle naïve aux opioïdes atteinte de cancer du sein, gynécologique ou de la tête et du cou a été étudiée. Les patient·es étaient considéré·es comme naïfs ou naïves aux opioïdes si leurs antécédents d'utilisation d'opioïdes étaient inférieurs ou égaux à une dose quotidienne équivalente à 30 mg de morphine orale pendant moins de sept jours au cours des trois mois précédant la chirurgie. Nous avons recruté les participant·es éligibles par échantillonnage de commodité dans les services jusqu'à ce qu'au moins 102 personnes soient incluses dans l'analyse finale. Après le congé, nous avons fait un suivi téléphonique auprès des participant·es le 7e jour à l'aide d'un formulaire structuré comprenant des questions visant à identifier la dernière date et la dose d'opioïdes prise. Les jours équivalents de consommation d'opioïdes ont été calculés en fonction de leur utilisation dans les 24 heures précédant le congé et du nombre de doses prescrites pour le congé. Notre critère d'évaluation principal était la prévalence de la surprescription dans les trois spécialités chirurgicales, définie comme le nombre de patient·es prenant moins de 50 % des opioïdes reçus au congé dans les sept premiers jours suivant le congé. Nous avons examiné les prédicteurs d'incidents de surprescription en utilisant la régression de Poisson multivariée comme critère d'évaluation secondaire. RéSULTATS: Nous avons recruté 119 patient·es, et 107 patient·es ont été inclus·es dans l'analyse finale. Une surprescription d'opioïdes a été observée pour 59 patient·es sur 107 (55 %). À leur congé, ces personnes présentaient des scores de douleur moyens plus faibles sur l'échelle d'évaluation numérique, des scores moyens de gravité de la douleur plus faibles, des jours équivalents d'opioïdes prescrits plus élevés et n'avaient pas utilisé d'opioïdes dans les 24 heures précédant le congé. L'incidence de surprescription était 2,4 fois plus élevée chez les patient·es à qui l'on avait prescrit des opioïdes sans utilisation d'opioïdes dans les 24 heures (risque relatif [RR], 2,38; intervalle de confiance [IC] à 95 %, 1,30 à 4,35; P = 0,005). De même, l'incidence de surprescription était 1,7 fois plus élevée chez les patient·es qui avaient reçu des opioïdes 24 heures avant le congé et qui avaient reçu des opioïdes pendant cinq jours équivalents ou plus au moment du congé (RR, 1,67; IC 95 %, 1,09 à 2,56; P = 0,02). CONCLUSION: Notre étude montre qu'il y a eu surprescription d'opioïdes pour la majorité des patient·es recruté·es bénéficiant d'une chirurgie de cancer du sein, gynécologique ou de la tête et du cou. Des évaluations individualisées des besoins en opioïdes des patient·es dans les 24 heures avant leur congé et une administration pendant moins de cinq jours sont des considérations importantes pour réduire la surprescription chez les personnes naïves aux opioïdes après une chirurgie oncologique.
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BACKGROUND: The radiation dose to dysphagia and aspiration-related structures (DARS) for patients undergoing transoral robotic surgery (TORS) and post-operative radiation therapy (PORT) for primary oropharyngeal carcinoma is unknown. METHODS: This prospective study measured swallowing using the MD Anderson Dysphagia Inventory at baseline and then 12-months after PORT. Dosimetric parameters were collected. RESULTS: 19 patients were recruited between 2017 and 2019. Worse swallow function at 12-months after PORT was associated with dose-parameters to the oesophageal inlet muscle, superior pharyngeal constrictor muscle and cervical oesophagus. Mean dose, V50Gy, and V60Gy to the base of tongue and pharyngeal constrictors was significantly lower in those receiving PORT to the neck alone. CONCLUSION: Dose to DARS was lower in patients who received PORT to the neck alone. In patients treated with TORS and PORT, poorer swallowing outcomes at 12 months post-treatment were associated with increased dose to oesophageal inlet muscle, superior constrictor muscle, and cervical oesophagus.
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PURPOSE: We investigated attitudes and practices of healthcare professionals (HCPs) to medicinal cannabis (MC) and complementary and integrative medicine (CIM), including individual therapies, such as acupuncture, massage, herbs, dietary supplements, nutrition and exercise. We explored whether healthcare occupation influenced attitudes to CIM and MC; referral pathways for advice on CIM; and interest in a pharmacy service to evaluate herbs and supplements. METHODS: Cross-sectional survey. All clinical staff at a comprehensive cancer hospital were invited to complete an anonymous questionnaire about CIM and MC. We used descriptive analysis to describe the respondent's knowledge and attitudes, and Fisher's exact test to test for differences by occupation, length of time at the hospital and age. RESULTS: Most of the 116 HCPs respondents supported integrating CIM into cancer care (94.8%) and wanted to learn more (90%) and to understand benefits and contraindications. Most respondents believed that CIM (87.9%) could benefit patients with cancer, and MC could benefit those with advanced cancer (49-51%). Whilst just over half (52.6%) felt confident discussing CIM with patients, only 10% felt they had sufficient knowledge to discuss MC. Most felt they did not have sufficient knowledge to specifically discuss mind and body practices (63.8%) or herbs and supplements (79%). HCPs (63%) would be more inclined to allow use of herbs and supplements with cancer treatment if a pharmacy service was available to evaluate interactions. Occupation, length of time at hospital and age influenced confidence and knowledge about CIM. CONCLUSIONS: The integration of evidence-based CIM and MC into cancer care is hampered by a lack of knowledge of benefits and contraindications, and gaps in education. Effective and safe integration may require targeted development of services such as pharmacy to evaluate the safety of herbs and supplements, and inclusion of cancer specialists who have received training in individual CIM therapies and MC.
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Medicina Integrativa , Maconha Medicinal , Neoplasias , Humanos , Maconha Medicinal/uso terapêutico , Estudos Transversais , Institutos de Câncer , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Austrália , Atenção à SaúdeRESUMO
BACKGROUND: The order of significance of clinicopathologic characteristics for the prognosis of patients with regional metastases from head and neck cutaneous squamous cell carcinoma (HNcSCC) is not well characterized. This study aimed to understand the impact of the known characteristics, including the presence of immunosuppression, number of deposits, largest deposit size, location and laterality of deposits, and presence of extranodal extension (ENE) on overall survival (OS) and disease-specific survival (DSS). METHODS: A retrospective study of 366 patients treated with curative intent for HNcSCC with regional metastatic disease was undertaken using recursive partitioning analysis (RPA). RESULTS: Using RPA modeling, the study determined that number of metastatic deposits carried the highest impact for both OS and DSS, followed by largest deposit size. The presence of ENE and immunosuppression was less significant. CONCLUSIONS: The results from this study provide new evidence for identifying and stratifying high-risk patients with metastatic HNcSCC. This information will be valuable in determining future HNcSCC staging systems.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Extensão Extranodal , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Metástase Linfática , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: To report treatment patterns and survival outcomes of patients with relapsed and refractory metastatic germ cell tumours (GCTs) treated with high-dose chemotherapy (HDCT) and autologous stem-cell transplantation in low-volume specialized centres within the widely dispersed populations of Australia and New Zealand between 1999 and 2019. PATIENTS AND METHODS: We conducted a retrospective analysis of 111 patients across 13 institutions. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. We reviewed treatment regimens, survival outcomes, deliverability and toxicities. Primary endpoints included overall (OS) and progression-free survival (PFS). Cox proportional hazards models were used to test the association of survival outcomes with patient and treatment factors. RESULTS: The median (range) age was 30 (14-68) years and GCT histology was non-seminomatous in 84% of patients. International Prognostic Factors Study Group (IPFSG) prognostic risk category was very low/low, intermediate, high and very high in 18%, 36%, 25% and 21% of patients, respectively. Salvage conventional-dose chemotherapy (CDCT) was administered prior to HDCT in 59% of patients. Regimens included paclitaxel, ifosfamide, carboplatin and etoposide (50%), carboplatin and etoposide (CE; 28%), carboplatin, etoposide and ifosfamide (CEI; 6%), carboplatin, etoposide and cyclophosphamide (CEC; 5%), CEC-paclitaxel (6%) and other (5%). With a median follow-up of 4.4 years, the 1-, 2- and 5-year PFS rates were 62%, 57% and 52%, respectively, and OS rates were 73%, 65% and 61%, respectively. There were five treatment-related deaths. Progression on treatment occurred in 17%. In a univariable analysis, worse International Germ Cell Cancer Collaborative Group (IGCCCG) and IPFSG prognostic groups were associated with inferior survival outcomes. An association of inferior survival was not found with the number of high-dose cycles received nor when HDCT was delivered after salvage CDCT. CONCLUSION: This large dual-national registry-based study reinforces the efficacy and deliverability of HDCT for relapsed and refractory metastatic GCT in low-volume specialized centres in Australia and New Zealand, with survival outcomes comparable to those found in international practice.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina , Intervalo Livre de Doença , Etoposídeo/uso terapêutico , Humanos , Ifosfamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Terapia de Salvação , Neoplasias Testiculares/patologiaRESUMO
BACKGROUND: The classical linear model is widely used in the analysis of clinical trials with continuous outcomes. However, required model assumptions are frequently not met, resulting in estimates of treatment effect that can be inefficient and biased. In addition, traditional models assess treatment effect only on the mean response, and not on other aspects of the response, such as the variance. Distributional regression modelling overcomes these limitations. The purpose of this paper is to demonstrate its usefulness for the analysis of clinical trials, and superior performance to that of traditional models. METHODS: Distributional regression models are demonstrated, and contrasted with normal linear models, on data from the LIPID randomized controlled trial, which compared the effects of pravastatin with placebo in patients with coronary heart disease. Systolic blood pressure (SBP) and the biomarker midregional pro-adrenomedullin (MR-proADM) were analysed. Treatment effect was estimated in models that used response distributions more appropriate than the normal (Box-Cox-t and Johnson's Su for MR-proADM and SBP, respectively), applied censoring below the detection limit of MR-proADM, estimated treatment effect on distributional parameters other than the mean, and included random effects for longitudinal observations. A simulation study was conducted to compare the performance of distributional regression models with normal linear regression, under conditions mimicking the LIPID study. The R package gamlss (Generalized Additive Models for Location, Scale and Shape), which implements maximum likelihood estimation for distributional regression modelling, was used throughout. RESULTS: In all cases the distributional regression models fit the data well, in contrast to poor fits obtained for traditional models; for MR-proADM a small but significant treatment effect on the mean was detected by the distributional regression model and not the normal model; and for SBP a beneficial treatment effect on the variance was demonstrated. In the simulation study distributional models strongly outperformed normal models when the response variable was non-normal and heterogeneous; and there was no disadvantage introduced by the use of distributional regression modelling when the response satisfied the normal linear model assumptions. CONCLUSIONS: Distributional regression models are a rich framework, largely untapped in the clinical trials world. We have demonstrated a sample of the capabilities of these models for the analysis of trials. If interest lies in accurate estimation of treatment effect on the mean, or other distributional features such as variance, the use of distributional regression modelling will yield superior estimates to traditional normal models, and is strongly recommended. TRIAL REGISTRATION: The LIPID trial was retrospectively registered on ANZCTR on 27/04/2016, registration number ACTRN12616000535471 .
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Interpretação Estatística de Dados , Biomarcadores , Ensaios Clínicos como Assunto , HumanosRESUMO
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. OBJECTIVE: To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). METHODS: Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. RESULTS: Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. CONCLUSIONS: PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018.
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Terapia com Luz de Baixa Intensidade , Doença de Parkinson/terapia , COVID-19 , Humanos , Estudos Prospectivos , SARS-CoV-2RESUMO
BACKGROUND: Previous investigations of falls predictors in people with Parkinson's disease (PD) have used various statistical methods and categorization of falls outcomes. The impact of methodological differences on falls predictors has not been investigated. OBJECTIVES: To describe similarities and differences in predictors modelled for fall rates [negative binomial (NB), Poisson Inverse Gaussian (PIG) and quantile regression] and previously-reported predictors of time to second fall (Cox regression), i.e. past falls, motor fluctuations, disability, levodopa dose and balance impairment. To investigate whether predictors from quantile regression vary across subsets of fallers based on fall frequency. METHODS: Participants with PD (n = 229) were followed-up for 12 months. NB and PIG regression were used to determine predictors of fall rates, with the best fitting model reported. Quantile regression was used to determine predictors at higher (62nd, 70th, 80th) percentiles of the falls distribution. Univariate and multivariate analyses were performed. RESULTS: Predictors of fall rates were the same in NB and PIG multivariate models, with the PIG model fitting our data better. Past falls, disability and levodopa dose were associated with fall rates from PIG and quantile regression. Freezing of gait was associated with fall rates from PIG regression. Disease severity predicted less (70th percentile, approximately 2-4) and more (80th percentile, approximately ≥ 5) frequent falls, and anteroposterior stability also predicted less frequent falls (p < 0.05), from quantile regression. CONCLUSIONS: Not all predictors of time to second fall were predictors of fall rates. Quantile regression revealed some divergent predictors depending on the percentile of fall frequency examined.
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Acidentes por Quedas , Doença de Parkinson , Idoso , Idoso de 80 Anos ou mais , Feminino , Marcha , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Equilíbrio Postural , Índice de Gravidade de DoençaRESUMO
In clinical trials one traditionally models the effect of treatment on the mean response. The underlying assumption is that treatment affects the response distribution through a mean location shift on a suitable scale, with other aspects of the distribution (shape/dispersion/variance) remaining the same. This work is motivated by a trial in Parkinson's disease patients in which one of the endpoints is the number of falls during a 10-week period. Inspection of the data reveals that the Poisson-inverse Gaussian (PiG) distribution is appropriate, and that the experimental treatment reduces not only the mean, but also the variability, substantially. The conventional analysis assumes a treatment effect on the mean, either adjusted or unadjusted for covariates, and a constant dispersion parameter. On our data, this analysis yields a non-significant treatment effect. However, if we model a treatment effect on both mean and dispersion parameters, both effects are highly significant. A simulation study shows that if a treatment effect exists on the dispersion and is ignored in the modelling, estimation of the treatment effect on the mean can be severely biased. We show further that if we use an orthogonal parametrization of the PiG distribution, estimates of the mean model are robust to misspecification of the dispersion model. We also discuss inferential aspects that are more difficult than anticipated in this setting. These findings have implications in the planning of statistical analyses for count data in clinical trials.
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Bioestatística/métodos , Modelos Estatísticos , Viés , Distribuição Normal , Distribuição de Poisson , Análise de RegressãoRESUMO
BACKGROUND: Intracerebral haemorrhage (ICH) rates increase in winter months. We aimed to determine associations of ambient temperature with clinical severity and haematoma size in acute ICH among Chinese participants in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT1). METHODS: INTERACT1 was a randomised controlled trial of early intensive blood pressure lowering in 404 patients with acute ICH. Among 304 (79%) Chinese participants, data on ambient temperature (average, minimum, maximum and range) on the day of ICH onset obtained from the China Meteorological Data Sharing Service System were linked to measures of clinical severity: elevated National Institute of Health Stroke Scale score (>10), low Glasgow Coma Scale score (<14), and haematoma parameters at the time of presentation. Clinical outcomes were evaluated in logistic regression models, and haematoma volume (log transformed, with and without intraventricular haemorrhage, IVH) was evaluated in multivariable regression models. RESULTS: No significant associations were evident between temperature parameters and clinical parameters and haematoma volume (with and without IVH), even after adjustment for key prognostic factors. CONCLUSIONS: No relationship was evident between ambient temperature and severity in acute ICH.
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Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiologia , Temperatura , Idoso , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Although road traffic injury is reported as the leading cause of work-related death in Australia, it is not clear, due to limitations in previous methods used, just how large a burden it is. Many organisations are unaware of the extent of work-related road traffic injury and, importantly, what can be done to reduce the burden. The proposed research will (i) estimate the prevalence of work-related road traffic injury and (ii) identify the organisational determinants associated with work-related road traffic injury. METHODS AND DESIGN: The current study is designed to enumerate the problem and identify the individual driver-level, the supervisor-level and organisational-level factors associated with work-related road traffic injury. The multilevel systems protocol will involve a series of cross-sectional surveys administered to drivers of fleet vehicles (n=1200), supervisors of the drivers (n=1200) and senior managers (n=300) within the same organisation. DISCUSSION: The novel use of the multilevel systems protocol is critical to be able to accurately assess the specific determinants of driving safety within each context of an organisation. RESULTS: The results are expected to highlight that reducing injury in the workplace requires more than just individual compliance with safety procedures. It will also establish, for the first time, an occupational translation taskforce to ensure that the research findings are adopted into work-place practice and thereby directly contribute to reductions in work-related road traffic injury.
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Acidentes de Trabalho/prevenção & controle , Acidentes de Trânsito/prevenção & controle , Acidentes de Trabalho/estatística & dados numéricos , Acidentes de Trânsito/estatística & dados numéricos , Austrália , Condução de Veículo/normas , Humanos , SegurançaRESUMO
INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of neurotoxic chemotherapy. Acute symptoms of CIPN during treatment can lead to dose reduction and cessation. Trials using electroacupuncture (EA) to treat established CIPN postchemotherapy have shown some efficacy. The current trial aims to assess the feasibility and preliminary efficacy of using EA to treat CIPN during chemotherapy. METHODS AND ANALYSIS: The current study is a single-centre, 1:1 randomised, sham-controlled pilot study set in a tertiary cancer hospital in Sydney, Australia, and will recruit 40 adult patients with early breast cancer undergoing adjuvant or neoadjuvant paclitaxel chemotherapy. Patients who develop CIPN within the first 6 weeks of chemotherapy will receive either true EA or sham-EA once a week for 10 weeks. The coprimary endpoints are recruitment and adherence rate, successful blinding of patients and compliance with the follow-up period. Secondary endpoints are mean change of CIPN symptoms from randomisation to end of treatment, sustained change in CIPN symptoms at 8-week and 24-week follow-up postchemotherapy, proportion of subjects attaining completion of 12 weeks of chemotherapy without dose reduction or cessation, change in acupuncture expectancy response pretreatment, during treatment and posttreatment. The primary assessment tool for the secondary endpoints will be a validated patient-reported outcome measure (European Organisation for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy) captured weekly from randomisation to week 12 of chemotherapy. ETHICS AND DISSEMINATION: The study protocol (2021/ETH12123) has been approved by the institutional Human Research Ethics Committee at St Vincent's Hospital Sydney and Chris O'Brien Lifehouse. Informed consent will be obtained prior to starting study-related procedures. The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000081718.
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Antineoplásicos , Neoplasias da Mama , Eletroacupuntura , Doenças do Sistema Nervoso Periférico , Adulto , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/terapia , Taxoides/efeitos adversos , Antineoplásicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Advances in genomics have enabled anticancer therapies to be tailored to target specific genomic alterations. Single-arm trials (SATs), including those incorporated within umbrella, basket, and platform trials, are widely adopted when it is not feasible to conduct randomized controlled trials in rare biomarker-defined subpopulations. External controls (ECs), defined as control arm data derived outside the clinical trial, have gained renewed interest as a strategy to supplement evidence generated from SATs to allow comparative analysis. There are increasing examples demonstrating the application of EC in precision oncology trials. The prospective application of EC in conducting comparative studies is associated with distinct methodological challenges, the specific considerations for EC use in biomarker-defined subpopulations have not been adequately discussed, and a formal framework is yet to be established. In this review, we present a framework for conducting a prospective comparative analysis using EC. Key steps are (1) defining the purpose of using EC to address the study question, (2) determining if the external data are fit for purpose, (3) developing a transparent study protocol and a statistical analysis plan, and (iv) interpreting results and drawing conclusions on the basis of a prespecified hypothesis. We specify the considerations required for the biomarker-defined subpopulations, which include (1) specifying the comparator and biomarker status of the comparator group, (2) defining lines of treatment, (3) assessment of the biomarker testing panels used, and (4) assessment of cohort stratification in tumor-agnostic studies. We further discuss novel clinical trial designs and statistical techniques leveraging EC to propose future directions to advance evidence generation and facilitate drug development in precision oncology.
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Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Medicina de Precisão , Oncologia , Resultado do Tratamento , BiomarcadoresRESUMO
BACKGROUND: Using comprehensive plasma lipidomic profiling from men with metastatic castration-resistant prostate cancer (mCRPC), we have previously identified a poor-prognostic lipid profile associated with shorter overall survival (OS). In order to translate this biomarker into the clinic, these men must be identifiable via a clinically accessible, regulatory-compliant assay. METHODS: A single regulatory-compliant liquid chromatography-mass spectrometry assay of candidate lipids was developed and tested on a mCRPC Discovery cohort of 105 men. Various risk-score Cox regression prognostic models of OS were built using the Discovery cohort. The model with the highest concordance index (PCPro) was chosen for validation and tested on an independent Validation cohort of 183 men. RESULTS: PCPro, the lipid biomarker, contains Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1), triglycerides and total cholesterol. Within the Discovery and Validation cohorts, men who were PCPro positive had significantly shorter OS compared to those who were PCPro negative (Discovery: median OS 12.0 months vs 24.2 months, hazard ratio (HR) 3.75 [95% confidence interval (CI) 2.29-6.15], p < 0.001, Validation: median OS 13.0 months vs 25.7 months, HR = 2.13 [95% CI 1.46-3.12], p < 0.001). CONCLUSIONS: We have developed PCPro, a lipid biomarker assay capable of prospectively identifying men with mCRPC with a poor prognosis. Prospective clinical trials are required to determine if men who are PCPro positive will benefit from therapeutic agents targeting lipid metabolism.
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Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Prospectivos , Biomarcadores , Prognóstico , LipídeosRESUMO
INTRODUCTION: Neoadjuvant therapy has become a standard treatment for patients with stage II/III HER2 positive and triple negative breast cancer, and in well-selected patients with locally advanced and borderline resectable high risk, luminal B breast cancer. Side effects of neoadjuvant therapy, such as fatigue, cardiotoxicity, neurotoxicity, anxiety, insomnia, vasomotor symptoms, gastrointestinal disturbance as well as a raft of immune-related adverse events, may impact treatment tolerance, long-term outcomes, and quality of life. Providing early supportive care prior to surgery (typically termed 'prehabilitation') may mitigate these side effects and improve quality of life.During our codesign of the intervention, consumers and healthcare professionals expressed desire for a programme that 'packaged' care, was easy to access, and was embedded in their care pathway. We hypothesise that a multimodal supportive care programme including exercise and complementary therapies, underpinned by behavioural change theory will improve self-efficacy, quality of life, readiness for surgery and any additional treatment for women with breast cancer. We seek to explore cardiometabolic, residual cancer burden and surgical outcomes, along with chemotherapy completion (relative dose intensity). This article describes the protocol for a feasibility study of a multimodal prehabilitation programme. METHODS AND ANALYSIS: This is a prospective, mixed-method, feasibility study of a multi-modal programme in a hospital setting for 20-30 women with breast cancer receiving neoadjuvant therapy. Primary outcomes are recruitment rate, retention rate, adherence and acceptability. Secondary outcomes include patient reported outcome measures (PROMs), surgical outcomes, length of stay, satisfaction with surgery, chemotherapy completion rates, changes in metabolic markers and adverse events. Interviews and focus groups to understand the experience with prehabilitation and different factors that may affect feasibility of the intervention . The output of this study will be a codesigned, evidence-informed intervention assessed for feasibility and acceptability by women with breast cancer and the healthcare professionals that care for them. ETHICS AND DISSEMINATION: The study received ethics approval from the St Vincents Hospital HREC (HREC/2021/ETH12198). Trial results will be communicated to participants, healthcare professionals, and the public via publication and conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000584730.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Terapia por Exercício/métodos , Estudos de Viabilidade , Terapia Neoadjuvante , Qualidade de Vida , Exercício Pré-Operatório , Estudos Prospectivos , Institutos de CâncerRESUMO
BACKGROUND: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. METHODS: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery±adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. RESULTS: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. CONCLUSION: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos , Prognóstico , Estadiamento de NeoplasiasRESUMO
OBJECTIVE: To investigate whether baseline joint space narrowing (JSN) predicted disease remission, knee pain, and physical function changes in persons with knee osteoarthritis (OA). METHODS: This study is a secondary analysis of a two-armed randomized controlled trial. Participants were aged ≥50 years (n = 171) with a body mass index ≥28 kg/m2 and radiographic medial tibiofemoral OA. Participants in the intervention group received diet and exercise programs and special treatment (cognitive behavioral therapy, knee brace, and muscle strengthening exercises) according to the disease remission. Remission of pain and remission of patient global assessment of disease activity and/or functional impairment were used to define the disease remission. The control group were provided with an education pamphlet. The primary outcome was disease remission at 32 weeks, and the secondary outcomes were the changes in knee pain and physical function at 20 and 32 weeks. Baseline JSN was scored from 0 to 3, and the association between baseline JSN and outcomes was assessed using multiple regression. RESULTS: There was no association of baseline JSN with disease remission at 32 weeks when the disease remission has been achieved. The baseline JSN grade 3 was associated with changes in knee pain at 20 weeks (p < .05). There was no association between baseline JSN and physical function. CONCLUSION: Baseline JSN severity predicted changes in knee pain but not the disease remission or changes in physical functions. Identification of baseline radiographic severity may be helpful in identifying differences in response to diet and exercise programs in knee OA.