Study of diffusion weighted MRI as a predictive biomarker of response during radiotherapy for high and intermediate risk squamous cell cancer of the oropharynx: The MeRInO study

Introduction and background: A significant proportion of patients with intermediate and high risk squamous cell cancer of the oropharynx (OPSCC) continue to relapse locally despite radical chemoradiotherapy (CRT). The toxicity of the current combination of intensified dose per fraction radiotherapy and platinum based chemotherapy limits further uniform intensification. If a predictive biomarker for outcomes from CRT can be identified during treatment then individualised and adaptive treatment strategies may be employed. Methods/design: The MeRInO study is a prospective observational imaging study of patients with intermediate and high risk, locally advanced OPSCC receiving radical RT or concurrent CRT Patients undergo diffusion weighted MRI prior to treatment (MRI_1) and during the third week of RT (MRI_2). Apparent diffusion coefficient (ADC) measurements will be made on each scan for previously specified target lesions (primary and lymph nodes) and change in ADC calculated. Patients will be followed up and disease status for each target lesion noted. The primary aim of the MeRInO study is to determine the threshold change in ADC from baseline to week 3 of RT that may identify the sub-group of non-responders during treatment. Discussion: The use of DW-MRI as a predictive biomarker during RT for SCC H&N is in its infancy but studies to date have found that response to treatment may indeed be predicted by comparison of DW-MRI carried out before and during treatment. However, previous studies have included all sub-sites and biological sub-types. Establishing ADC thresholds that predict for local failure is an essential step towards using DW-MRI to improve the therapeutic ratio in treating SCC H&N. This would be done most robustly in a specific H&N sub-site and in sub-types with similar biological behaviour. The MeRInO study will help establish these thresholds in OPSCC

The relative importance of frailty, physical and cardiovascular function as exercise-modifiable predictors of falls in haemodialysis patients: A prospective cohort study

From PubMed via Jisc Publications RouterTobia Zanotto - ORCID 0000-0002-6571-4763 https://orcid.org/0000-0002-6571-4763Marietta van der Linden - ORCID 000-0003-2256-6673 https://orcid.org/0000-0003-2256-6673Stage 5 chronic kidney disease (CKD-5) patients on haemodialysis (HD) are at high risk of accidental falls. Previous research has shown that frailty is one of the primary contributors to the increased risk of falling in this clinical population. However, HD patients often present with abnormalities of cardiovascular function such as baroreflex impairment and orthostatic dysregulation of blood pressure (BP) which may also be implicated in the aetiology of falling. Therefore, we aimed to explore the relative importance of frailty and cardiovascular function as potential exercise-modifiable predictors of falls in these patients. Ninety-three prevalent CKD-5 patients on HD from three Renal Units were recruited for this prospective cohort study, which was conducted between October 2015 and August 2018. At baseline, frailty status was assessed using the Fried's frailty phenotype, while physical function was evaluated through timed up and go (TUG), five repetitions chair sit-to-stand (CSTS-5), objectively measured physical activity, and maximal voluntary isometric strength. Baroreflex and haemodynamic function at rest and in response to a 60° head-up tilt test (HUT-60°) were also assessed by means of the Task Force Monitor. The number of falls experienced was recorded once a month during 12 months of follow-up. In univariate negative binomial regression analysis, frailty (RR: 4.10, 95%CI: 1.60-10.51, p = 0.003) and other physical function determinants were associated with a higher number of falls. In multivariate analysis however, only worse baroreflex function (RR: 0.96, 95%CI: 0.94-0.99, p = 0.004), and orthostatic decrements of BP to HUT-60° (RR: 0.93, 95%CI: 0.87-0.99, p = 0.033) remained significantly associated with a greater number of falls. Eighty falls were recorded during the study period and the majority of them (41.3%) were precipitated by dizziness symptoms, as reported by participants. This prospective study indicates that cardiovascular mechanisms implicated in the short-term regulation of BP showed a greater relative importance than frailty in predicting falls in CKD-5 patients on HD. A high number of falls appeared to be mediated by a degree of cardiovascular dysregulation, as evidenced by the predominance of self-reported dizziness symptoms. ClinicalTrials.gov (trial registration ID: NCT02392299; date of registration: March 18, 2015).This work was supported by a British Kidney Patient Association – British Renal Society joint grant (BKPA-BRS grant number: 16–003). The funders of this study had no role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.21pubpu

Advocacy in the tail: Exploring the implications of ‘climategate’ for science journalism and public debate in the digital age

This paper explores the evolving practices of science journalism and public debate in the digital age. The vehicle for this study is the release of digitally stored email correspondence, data and documents from the Climatic Research Unit at the University of East Anglia in the weeks immediately prior to the United Nations Copenhagen Summit (COP-15) in December 2009. Described using the journalistic shorthand of ‘climategate’, and initially promoted through socio-technical networks of bloggers, this episode became a global news story and the subject of several formal reviews. ‘Climategate’ illustrates that media literate critics of anthropogenic explanations of climate change used digital tools to support their cause, making visible selected, newsworthy aspects of scientific information and the practices of scientists. In conclusion, I argue that ‘climategate’ may have profound implications for the production and distribution of science news, and how climate science is represented and debated in the digitally-mediated public sphere

Patient-reported barriers to accepting a technological adherence package in the MAGNIFY trial.

Peer reviewedPostprin

Maximizing Adherence and Gaining New Information For Your Chronic Obstructive Pulmonary Disease (MAGNIFY COPD):Study Protocol for the Pragmatic, Cluster Randomized Trial Evaluating the Impact of Dual Bronchodilator with Add-On Sensor and Electronic Monitoring on Clinical Outcomes

Background: Poor treatment adherence in COPD patients is associated with poor clinical outcomes and increased healthcare burden. Personalized approaches for adherence management, supported with technology-based interventions, may offer benefits to patients and providers but are currently unproven in terms of clinical outcomes as opposed to adherence outcomes. Methods: Maximizing Adherence and Gaining New Information For Your COPD (MAGNIFY COPD study), a pragmatic cluster randomized trial, aims to evaluate the impact of an adherence technology package (interventional package), comprising an adherence review, ongoing provision of a dual bronchodilator but with an add-on inhaler sensor device and a connected mobile application. This will compare time to treatment failure and other clinical outcomes in patients identified at high risk of exacerbations with historic poor treatment adherence as measured by prescription collection to mono/dual therapy over one year (1312 patients) versus usual care. Treatment failure is defined as the first occurrence of one of the following: (1) moderate/severe COPD exacerbation, (2) prescription of triple therapy (inhaled corticosteroid/long-acting β2-agonist/long-acting muscarinic antagonist [ICS/LABA/LAMA]), (3) prescription of additional chronic therapy for COPD, or (4) respiratory-related death. Adherence, moderate/severe exacerbations, respiratory-related healthcare resource utilization and costs, and intervention package acceptance rate will also be assessed. Eligible primary care practices (N=176) participating in the Optimum Patient Care Quality Improvement Program will be randomized (1:1) to either adherence support cluster arm (suitable patients already receiving or initiated Ultibro® Breezhaler® [indacaterol/glycopyrronium] will be offered interventional package) or the control cluster arm (suitable patients continue to receive usual clinical care). Patients will be identified and outcomes collected from anonymized electronic medical records within the Optimum Patient Care Research Database. On study completion, electronic medical record data will be re-extracted to analyze outcomes in both study groups. Registration Number: ISRCTN10567920. Conclusion: MAGNIFY will explore patient benefits of technology-based interventions for electronic adherence monitoring

Regulated deficit irrigation reduces water use of almonds without affecting yield

A plant-based regulated deficit irrigation (RDI) experiment in the northern Sacramento Valley determined that crop consumptive water use and irrigation could be reduced without significant detrimental effects on almond production. Tree stress was measured by recording midday stem water potential, a direct measure of tree water stress. With a water stress level of −14 to −18 bars during the hull-split period, average annual water savings were about 5 inches. Over 5 years, no significant yield reductions were observed, although average kernel weight was slightly lower. The results suggest that water savings can be achieved without affecting yield, even in soils with low water-holding capacity

Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): Study protocol for a randomized phase III trial

Background: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4-10 metastatic cancer lesions. Methods: One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. Discussion: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4-10 oligometastatic lesions. Trial registration: Clinicaltrials.gov identifier: NCT03721341. Date of registration: October 26, 2018

Baroreflex function, haemodynamic responses to an orthostatic challenge, and falls in haemodialysis patients

From PLOS via Jisc Publications Router.History: collection 2018, received 2018-05-24, accepted 2018-11-12, epub 2018-12-06Publication status: PublishedBackground Stage 5 chronic kidney disease patients on haemodialysis (HD) often present with dizziness and pre-syncopal events as a result of the combined effect of HD therapy and cardiovascular disease. The dysregulation of blood pressure (BP) during orthostasis may be implicated in the aetiology of falls in these patients. Therefore, we explored the relationship between baroreflex function, the haemodynamic responses to a passive orthostatic challenge, and falls in HD patients. Methods Seventy-six HD patients were enrolled in this cross-sectional study. Participants were classified as “fallers” and “non-fallers” and completed a passive head up tilting to 60o (HUT-60°) test on an automated tilt table. ECG signals, continuous and oscillometric BP measurements and impedance cardiography were recorded. The following variables were derived from these measurements: heart rate (HR) stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), number of baroreceptor events, and baroreceptor effectiveness index (BEI). Results The forty-four participants who were classified as fallers (57.9%) had a lower number of baroreceptor events (6.5±8.5 vs 14±16.7, p = .027) and BEI (20.8±24.2% vs 33.4±23.3%, p = .025). In addition, fallers experienced a significantly larger drop in systolic (-6.4±10.9 vs -0.4±7.7 mmHg, p = .011) and diastolic (-2.7±7.3 vs 1.8±6 mmHg, p = .027) oscillometric BP from supine to HUT-60° compared with non-fallers. None of the variables taken for the analysis were significantly associated with falls in multivariate logistic regression analysis. Conclusions This cross-sectional comparison indicates that, at rest, HD patients with a positive history of falls present with a lower count of baroreceptor sequences and BEI. Short-term BP regulation warrants further investigation as BP drops during a passive orthostatic challenge may be implicated in the aetiology of falls in HD

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding: UK Research and Innovation and National Institute for Health Research.UK Research and Innovation and National Institute for Health Research