Study protocol for a randomized trial of a supportive care mobile application to improve symptoms, coping, and quality of life in patients with advanced non-small cell lung cancer

Patients with advanced non-small cell lung cancer (NSCLC) often experience burdensome symptoms, emotional distress, and poor quality of life (QOL). While national guidelines recommend early palliative care to address these supportive care needs, most patients with advanced NSCLC lack access to such comprehensive care. Our aim in the current study is to test a novel model of palliative care delivery and use of innovative technology to evaluate the feasibility, acceptability, and preliminary efficacy of a supportive care mobile application (app) for improving symptom management and adaptive coping in patients with advanced NSCLC. We will enroll 120 patients with unresectable Stage III or IV NSCLC diagnosed within the past 12 weeks receiving care with palliative intent at a major academic comprehensive cancer center and its community affiliates. The study will take place in two phases, the first of which will be dedicated to adapting an evidence-based, early palliative care treatment guide and prior supportive care mobile app intervention to address the specific symptom management and coping needs of patients with advanced NSCLC. The second phase of the study will be a two-group, randomized controlled trial. Study patients will complete baseline self-report measures of symptoms, mood, coping skills, and QOL, after which they will be randomized to receive either the mobile app intervention combined with usual oncology care or usual oncology care alone. Intervention patients will use a tablet computer to self-administer the mobile app, which consists of six modules that teach evidence-based skills for managing burdensome symptoms and coping effectively with advanced cancer and its treatment. At 12 weeks follow up, patients in both groups will repeat the same self-report measures. We will use descriptive statistics to determine feasibility metrics of enrollment and retention rates. For secondary self-report measures, we will use linear regression controlling for baseline values. The results of the present study will contribute to a growing body of evidence regarding the supportive care needs of patients with advanced cancer and will have implications for how best to use innovative technology to widely disseminate comprehensive supportive care services to all patients who may benefit.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier[NCT04629300]

Deglacierization of a marginal basin and implications for outburst floods

This article was submitted to Cryospheric Sciences, a section of the journal Frontiers in Earth ScienceSuicide Basin is a partly glacierized marginal basin of Mendenhall Glacier, Alaska, that has released glacier lake outburst floods (GLOFs) annually since 2011. The floods cause inundation and erosion in the Mendenhall Valley, impacting homes and other infrastructure. Here, we utilize in-situ and remote sensing data to assess the recent evolution and current state of Suicide Basin. We focus on the 2018 and 2019 melt seasons, during which we collected most of our data, partly using unmanned aerial vehicles (UAVs). To provide longer-term context, we analyze DEMs collected since 2006 and model glacier surface mass balance over the 2006–2019 period. During the 2018 and 2019 outburst flood events, Suicide Basin released ∼ 30 Å~ 106 m3 of water within approximately 4–5 days. Since lake drainage was partial in both years, these ∼ 30 Å~ 106 m3 represent only a fraction (∼ 60%) of the basin’s total storage capacity. In contrast to previous years, subglacial drainage was preceded by supraglacial outflow over the ice dam, which lasted ∼ 1 day in 2018 and 6 days in 2019. Two large calving events occurred in 2018 and 2019, with submerged ice breaking off the main glacier during lake filling, thereby increasing the basin’s storage capacity. In 2018, the floating ice in the basin was 36 m thick on average. In 2019, ice thickness was 29 m, suggesting rapid decay of the ice tongue despite increasing ice inflow from Mendenhall Glacier. The ice dam at the basin entrance thinned by more than 5 m a–1 from 2018 to 2019, which is approximately double the rate of the reference period 2006–2018. While ice-dam thinning reduces water storage capacity in the basin, that capacity is increased by declining ice volume in the basin and longitudinal lake expansion, with the latter process challenging to predict. The potential for premature drainage onset (i.e., drainage before the lake’s storage capacity is reached), intermittent drainage decelerations, and early drainage termination further complicates prediction of future GLOF events.This work was funded by the Alaska Climate Adaptation Science Center (AK CASC). UAVs and other surveying equipment were partly funded through the U.S. National Science Foundation (NSF) award EAR-1921598. EH and SH were partially supported by the NSF award OIA-1753748 and the State of Alaska. Streamflow monitoring of the Mendenhall River and real-time imagery of Suicide Basin were funded by the U.S. Geological Survey Groundwater and Streamflow Information Program. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Ye

A survey of factors associated with the successful recognition of agonal breathing and cardiac arrest by 9-1-1 call takers: design and methodology

<p>Abstract</p> <p>Background</p> <p>Cardiac arrest victims most often collapse at home, where only a modest proportion receives life-saving bystander cardiopulmonary resuscitation. As many as 40% of all sudden cardiac arrest victims have agonal or abnormal breathing in the first minutes following cardiac arrest. 9-1-1 call takers may wrongly interpret agonal breathing as a sign of life, and not initiate telephone cardiopulmonary resuscitation instructions. Improving 9-1-1 call takers' ability to recognize agonal breathing as a sign of cardiac arrest could result in improved bystander cardiopulmonary resuscitation and survival rates for out-of-hospital cardiac arrest victims.</p> <p>Methods/Design</p> <p>The overall goal of this study is to design and conduct a survey of 9-1-1 call takers in the province of Ontario to better understand the factors associated with the successful identification of cardiac arrest (including patients with agonal breathing) over the phone, and subsequent administration of cardiopulmonary resuscitation instructions to callers. This study will be conducted in three phases using the Theory of Planned Behaviour. In Phase One, we will conduct semi-structured qualitative interviews with a purposeful selection of 9-1-1 call takers from Ontario, and identify common themes and belief categories. In Phase Two, we will use the qualitative interview results to design and pilot a quantitative survey. In Phase Three, a final version of the quantitative survey will be administered via an electronic medium to all registered call takers in the province of Ontario. We will perform qualitative thematic analysis (Phase One) and regression modelling (Phases Two and Three), to determine direct and indirect relationship of behavioural constructs with intentions to provide cardiopulmonary resuscitation instructions.</p> <p>Discussion</p> <p>The results of this study will provide valuable insight into the factors associated with the successful recognition of agonal breathing and cardiac arrest by 9-1-1 call takers. This will guide future interventional studies, which may include continuing education and protocol changes, in order to help increase the number of callers appropriately receiving cardiopulmonary resuscitation instructions, and save the lives of more cardiac arrest victims.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00848588</p

Key criteria for developing ecosystem service indicators to inform decision making

Decision makers are increasingly interested in information from ecosystem services (ES) assessments. Scientists have for long recognised the importance of selecting appropriate indicators. Yet, while the amount and variety of indicators developed by scientists seems to increase continuously, the extent to which the indicators truly inform decision makers is often unknown and questioned. In this viewpoint paper, we reflect and provide guidance on how to develop appropriate ES indicators for informing decision making, building on scientific literature and practical experience collected from researchers involved in seven case studies. We synthesized 16 criteria for ES indicator selection and organized them according to the widely used categories of credibility, salience, legitimacy (CSL). We propose to consider additional criteria related to feasibility (F), as CSL criteria alone often seem to produce indicators which are unachievable in practice. Considering CSL & F together requires a combination of scientific knowledge, communication skills, policy and governance insights and on-field experience. We present a checklist to evaluate CSL & F of your ES indicators. This checklist helps to detect and mitigate critical shortcomings in an early phase of the development process, and aids the development of effective indicators to inform actual policy decisions

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Bedrock geology of DFDP-2B, central Alpine Fault, New Zealand

<p>During the second phase of the Alpine Fault, Deep Fault Drilling Project (DFDP) in the Whataroa River, South Westland, New Zealand, bedrock was encountered in the DFDP-2B borehole from 238.5–893.2 m Measured Depth (MD). Continuous sampling and meso- to microscale characterisation of whole rock cuttings established that, in sequence, the borehole sampled amphibolite facies, Torlesse Composite Terrane-derived schists, protomylonites and mylonites, terminating 200–400 m above an Alpine Fault Principal Slip Zone (PSZ) with a maximum dip of 62°. The most diagnostic structural features of increasing PSZ proximity were the occurrence of shear bands and reduction in mean quartz grain sizes. A change in composition to greater mica:quartz + feldspar, most markedly below c. 700 m MD, is inferred to result from either heterogeneous sampling or a change in lithology related to alteration. Major oxide variations suggest the fault-proximal Alpine Fault alteration zone, as previously defined in DFDP-1 core, was not sampled.</p

Petrophysical, Geochemical, and Hydrological Evidence for Extensive Fracture-Mediated Fluid and Heat Transport in the Alpine Fault's Hanging-Wall Damage Zone

International audienceFault rock assemblages reflect interaction between deformation, stress, temperature, fluid, and chemical regimes on distinct spatial and temporal scales at various positions in the crust. Here we interpret measurements made in the hanging‐wall of the Alpine Fault during the second stage of the Deep Fault Drilling Project (DFDP‐2). We present observational evidence for extensive fracturing and high hanging‐wall hydraulic conductivity (∼10−9 to 10−7 m/s, corresponding to permeability of ∼10−16 to 10−14 m2) extending several hundred meters from the fault's principal slip zone. Mud losses, gas chemistry anomalies, and petrophysical data indicate that a subset of fractures intersected by the borehole are capable of transmitting fluid volumes of several cubic meters on time scales of hours. DFDP‐2 observations and other data suggest that this hydrogeologically active portion of the fault zone in the hanging‐wall is several kilometers wide in the uppermost crust. This finding is consistent with numerical models of earthquake rupture and off‐fault damage. We conclude that the mechanically and hydrogeologically active part of the Alpine Fault is a more dynamic and extensive feature than commonly described in models based on exhumed faults. We propose that the hydrogeologically active damage zone of the Alpine Fault and other large active faults in areas of high topographic relief can be subdivided into an inner zone in which damage is controlled principally by earthquake rupture processes and an outer zone in which damage reflects coseismic shaking, strain accumulation and release on interseismic timescales, and inherited fracturing related to exhumation