15 research outputs found
The Project ENABLE Cornerstone Randomized Controlled Trial: Study Protocol for a Lay Navigator-led, Early Palliative Care Coaching Intervention for African American and Rural-dwelling Advanced Cancer Family Caregivers
Background: Family caregivers play a vital, yet stressful role in managing the healthcare needs and optimizing the quality of life of patients with advanced cancer, from the time they are newly diagnosed until end of life. While early telehealth palliative care has been found to effectively support family caregivers, little work has focused on historically under-resourced populations, particularly African American and rural-dwelling individuals. To address this need, we developed and are currently testing Project ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone, a lay navigator-led, early palliative care coaching intervention for family caregivers of African American and rural-dwelling patients with newly diagnosed advanced cancer.Methods: This is a 2-site, single-blind, hybrid type I implementation-effectiveness trial of the Cornerstone intervention versus usual care. Cornerstone is a multicomponent intervention based on Pearlin’s Stress-Health Process Model where African American and/or rural-dwelling family caregivers of patients with newly diagnosed advanced cancer (target sample size = 294 dyads) are paired with a lay navigator coach and receive a series of six, brief 20–60-min telehealth sessions focused on stress management and coping, caregiving skills, getting help, self-care, and preparing for the future/advance care planning. Subsequent to core sessions, caregivers receive monthly follow-up indefinitely until the patient’s death. Caregiver and patient outcomes are collected at baseline and every 12 weeks until the patient’s death (primary outcome: caregiver distress at 24 weeks; secondary outcomes: caregiver: quality of life and burden; patient: distress, quality of life, and healthcare utilization). Implementation costs and the intervention cost effectiveness are also being evaluated.Discussion: Should this intervention demonstrate efficacy, it would yield an implementation-ready model of early palliative care support for under-resourced family caregivers. A key design principle that has centrally informed the Cornerstone intervention is that every caregiving situation is unique and each caregiver faces distinct challenges that cannot be addressed using a one-size-fits all approach. Hence, Cornerstone employs culturally savvy lay navigator coaches who are trained to establish a strong, therapeutic alliance with participants and tailor their coaching to a diverse range of individual circumstances
A combination of urinary biomarker panel and PancRISK score for earlier detection of pancreatic cancer: A case–control study
Funder: Pancreatic Cancer Research Fund; funder-id: http://dx.doi.org/10.13039/100011704Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with around 9% of patients surviving >5 years. Asymptomatic in its initial stages, PDAC is mostly diagnosed late, when already a locally advanced or metastatic disease, as there are no useful biomarkers for detection in its early stages, when surgery can be curative. We have previously described a promising biomarker panel (LYVE1, REG1A, and TFF1) for earlier detection of PDAC in urine. Here, we aimed to establish the accuracy of an improved panel, including REG1B instead of REG1A, and an algorithm for data interpretation, the PancRISK score, in additional retrospectively collected urine specimens. We also assessed the complementarity of this panel with CA19-9 and explored the daily variation and stability of the biomarkers and their performance in common urinary tract cancers. Methods and findings: Clinical specimens were obtained from multiple centres: Barts Pancreas Tissue Bank, University College London, University of Liverpool, Spanish National Cancer Research Center, Cambridge University Hospital, and University of Belgrade. The biomarker panel was assayed on 590 urine specimens: 183 control samples, 208 benign hepatobiliary disease samples (of which 119 were chronic pancreatitis), and 199 PDAC samples (102 stage I–II and 97 stage III–IV); 50.7% were from female individuals. PDAC samples were collected from patients before treatment. The samples were assayed using commercially available ELISAs. Statistical analyses were performed using non-parametric Kruskal–Wallis tests adjusted for multiple comparisons, and multiple logistic regression. Training and validation datasets for controls and PDAC samples were obtained after random division of the whole available dataset in a 1:1 ratio. The substitution of REG1A with REG1B enhanced the performance of the panel to detect resectable PDAC. In a comparison of controls and PDAC stage I–II samples, the areas under the receiver operating characteristic curve (AUCs) increased from 0.900 (95% CI 0.843–0.957) and 0.926 (95% CI 0.843–1.000) in the training (50% of the dataset) and validation sets, respectively, to 0.936 in both the training (95% CI 0.903–0.969) and the validation (95% CI 0.888–0.984) datasets for the new panel including REG1B. This improved panel showed both sensitivity (SN) and specificity (SP) to be >85%. Plasma CA19-9 enhanced the performance of this panel in discriminating PDAC I–II patients from controls, with AUC = 0.992 (95% CI 0.983–1.000), SN = 0.963 (95% CI 0.913–1.000), and SP = 0.967 (95% CI 0.924–1.000). We demonstrate that the biomarkers do not show significant daily variation, and that they are stable for up to 5 days at room temperature. The main limitation of our study is the low number of stage I–IIA PDAC samples (n = 27) and lack of samples from individuals with hereditary predisposition to PDAC, for which specimens collected from control individuals were used as a proxy. Conclusions: We have successfully validated our urinary biomarker panel, which was improved by substituting REG1A with REG1B. At a pre-selected cutoff of >80% SN and SP for the affiliated PancRISK score, we demonstrate a clinically applicable risk stratification tool with a binary output for risk of developing PDAC (‘elevated’ or ‘normal’). PancRISK provides a step towards precision surveillance for PDAC patients, which we will test in a prospective clinical study, UroPanc
Development of a novel motivational interviewing (MI) informed peer-support intervention to support mothers to breastfeed for longer
Background: Many women in the UK stop breastfeeding before they would like to, and earlier than is recommended by the World Health Organization (WHO). Given the potential health benefits for mother and baby, new ways of supporting women to breastfeed for longer are required. The purpose of this study was to develop and characterise a novel Motivational Interviewing (MI) informed breastfeeding peer-support intervention. Methods: Qualitative interviews with health professionals and service providers (n=14), and focus groups with mothers (n=14), fathers (n=3), and breastfeeding peer-supporters (n=15) were carried out to understand experiences of breastfeeding peer-support and identify intervention options. Data were audio-recorded, transcribed, and analysed thematically. Consultation took place with a combined professional and lay Stakeholder Group (n=23). The Behaviour Change Wheel (BCW) guided intervention development process used the findings of the qualitative research and stakeholder consultation, alongside evidence from existing literature, to identify: the target behaviour to be changed; sources of this behaviour based on the Capability, Opportunity and Motivation (COM-B) model; intervention functions that could alter this behaviour; and; mode of delivery for the intervention. Behaviour change techniques included in the intervention were categorised using the Behaviour Change Technique Taxonomy Version 1 (BCTTv1). Results: Building knowledge, skills, confidence, and providing social support were perceived to be key functions of breastfeeding peer-support interventions that aim to decrease early discontinuation of breastfeeding. These features of breastfeeding peer-support mapped onto the BCW education, training, modelling and environmental restructuring intervention functions. Behaviour change techniques (BCTTv1) included social support, problem solving, and goal setting. The intervention included important inter-personal relational features (e.g. trust, honesty, kindness), and the BCTTv1 needed adaptation to incorporate this. Conclusions: The MI-informed breastfeeding peer-support intervention developed using this systematic and user-informed approach has a clear theoretical basis and well-described behaviour 3 change techniques. The process described could be useful in developing other complex interventions that incorporate peer-support and/or MI
RETRACTED ARTICLE: Multimorbidity: not just an older person’s issue. Results from an Australian biomedical study
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
Genome-wide association mapping of partial resistance to Phytophthora sojae in soybean plant introductions from the Republic of Korea
Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours
The lysyl oxidase (LOX) family of enzymes are a major driver in the biogenesis of desmoplastic matrix at the primary tumour and secondary metastatic sites. With the increasing interest in and development of anti-stromal therapies aimed at improving clinical outcomes of cancer patients, the Lox family has emerged as a potentially powerful clinical target. This review examines how lysyl oxidase family dysregulation in solid cancers contributes to disease progression and poor patient outcomes, as well as an evaluation of the preclinical landscape of LOX family targeting therapeutics. We also discuss the suitability of the LOX family as a diagnostic and/or prognostic marker in solid tumours
Evidence for an Early-Middle Jurassic fluid event constrained by Sm–Nd, Sr isotopes, rare earth elements and yttrium in the Bowen Basin, Australia
The Late Permian coal measures in the Bowen Basin, Australia, are extensively mineralized with calcite as cleat infilling and veins. This study utilised strontium and samarium‑neodymium isotope analyses as well as rare earth element and yttrium (REY) composition of vein calcites, from two boreholes in a faulted and intruded area within the Jellinbah Thrust Zone, to investigate the origin and timing of calcite precipitation. All samples showed low Sr isotopic ratios that overlapped the range typical of mantle materials, suggesting that fluids were derived from the mantle. The calcite veins in core from Dingonose 14, with two exceptions, exhibit very similar Sr isotopic ratios yet have large variations in REY patterns and a wide range in Sm–Nd ratios. These samples defined an isochron corresponding to an age of 174 ± 11 Ma, which may record the timing of fluid mobilization from the deeply buried part of the foreland basin during the Early and Middle Jurassic, prior to subsequent extension and uplift in the Late Cretaceous. This fluid event may be a response to the Gondwana supercontinent break-up during the Early-Middle Jurassic. Various thermal and chemical conditions resulted in the different REY patterns of calcite in Dingonose 14 core. Calcite veins in Summit 3 core showed extremely similar REY patterns and Sr isotopic ratios but different Sm–Nd isotopic compositions relative to Dingonose 14 core, with no Sm–Nd isochron able to be resolved. The structural geology of the Summit 3 locality is complex, having overturned beds and large veins of prismatic quartz present in addition to calcite, and potential for multiple periods of veining to have occurred. Hence the lack of Sm–Nd isotopic equilibrium for the Summit 3 samples is most likely due to multiple fluid events
An Early Palliative Care Telehealth Coaching Intervention to Enhance Advanced Cancer Family Caregivers’ Decision Support Skills: The CASCADE Pilot Factorial Trial
ContextPatients with advanced cancer often involve family caregivers in health-related decision-making from diagnosis to end-of-life; however, few interventions have been developed to enhance caregiver decision support skills.ObjectivesAssess the feasibility, acceptability, and potential efficacy of individual intervention components of CASCADE (CAre Supporters Coached to be Adept DEcision Partners), an early telehealth, palliative care coach-led decision support training intervention for caregivers.MethodsPilot factorial trial using the multiphase optimization strategy (October 2019-October 2020). Family caregivers and their care recipients with newly-diagnosed advanced cancer (n = 46 dyads) were randomized to1 of 8 experimental conditions that included a combination of one of the following three CASCADE components: 1) effective decision support psychoeducation; 2) decision support communication training; and 3) Ottawa Decision Guide training. Feasibility was assessed by completion of sessions and questionnaires (predefined as ≥80%). Acceptability was determined through postintervention interviews and participants' ratings of their likelihood to recommend. Measures of effective decision support and caregiver and patient distress were collected at Twelve and Twenty four weeks.ResultsCaregiver participants completed 78% of intervention sessions and 81% of questionnaires; patients completed 80% of questionnaires. Across conditions, average caregiver ratings for recommending the program to others was 9.9 on a scale from 1-Not at all likely to 10-Extremely likely. Individual CASCADE components were observed to have potential benefit for effective decision support and caregiver distress.ConclusionWe successfully piloted a factorial trial design to examine components of a novel intervention to enhance the decision support skills of advanced cancer family caregivers. A fully-powered factorial trial is warranted.Key messageWe pilot tested components of CASCADE, an early palliative care decision support training intervention for family caregivers of patients with advanced cancer. CASCADE components were acceptable and the trial design feasible, providing promising future directions for palliative care intervention development and testing. Pilot results will inform a fully-powered trial