Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Registration of Planar Film Radiographs with Computed Tomography

In this paper we describe a method to register Computed Tomography (CT) data with planar film radiographs. Previous methods applied to the problem of CT-radiograph registration rely on determining the correspondence between occluding contours of the 3D surface in the CT data with 2D contours in the projection image. These methods implicitly assume that the correspondence is accurate, ignoring fundamental nonlinear differences in the underlying measurements. In contrast, our emphasis has been to directly exploit the relationship between imaging devices. This is performed by registering radiograph data with intensity-corrected simulated radiograph data derived from CT measurements. We will show that by exploiting the physical relationship between CT and radiograph measurements we can significantly improve registration accuracy. Concomitantly, we detail the relationship between CT and radiograph measurements and the primary factors influencing discrepancies between simulated and real radiograph data

Physician Satisfaction with Chronic Care Processes: A Cluster-Randomized Trial of Guided Care

PURPOSE Chronically ill older patients with multiple conditions are challenging to care for, and new models of care for this population are needed. This study evaluates the effect of the Guided Care model on primary care physicians’ impressions of processes of care for chronically ill older patients

The Strategies to Reduce Injuries and Develop Confidence in Elders Intervention: Falls Risk Factor Assessment and Management, Patient Engagement, and Nurse Co-management.

In response to the epidemic of falls and serious falls-related injuries in older persons, in 2014, the Patient Centered Outcomes Research Institute (PCORI) and the National Institute on Aging funded a pragmatic trial, Strategies to Reduce Injuries and Develop confidence in Elders (STRIDE) to compare the effects of a multifactorial intervention with those of an enhanced usual care intervention. The STRIDE multifactorial intervention consists of five major components that registered nurses deliver in the role of falls care managers, co-managing fall risk in partnership with patients and their primary care providers (PCPs). The components include a standardized assessment of eight modifiable risk factors (medications; postural hypotension; feet and footwear; vision; vitamin D; osteoporosis; home safety; strength, gait, and balance impairment) and the use of protocols and algorithms to generate recommended management of risk factors; explanation of assessment results to the patient (and caregiver when appropriate) using basic motivational interviewing techniques to elicit patient priorities, preferences, and readiness to participate in treatments; co-creation of individualized falls care plans that patients' PCPs review, modify, and approve; implementation of the falls care plan; and ongoing monitoring of response, regularly scheduled re-assessments of fall risk, and revisions of the falls care plan. Custom-designed falls care management software facilitates risk factor assessment, the identification of recommended interventions, clinic note generation, and longitudinal care management. The trial testing the effectiveness of the STRIDE intervention is in progress, with results expected in late 2019