Seasonal Controls on Microbial Depolymerization and Oxidation of Organic Matter in Floodplain Soils.

Floodplain soils are vast reservoirs of organic carbon often attributed to anaerobic conditions that impose metabolic constraints on organic matter degradation. What remains elusive is how such metabolic constraints respond to dynamic flooding and drainage cycles characteristic of floodplain soils. Here we show that microbial depolymerization and respiration of organic compounds, two rate-limiting steps in decomposition, vary spatially and temporally with seasonal flooding of mountainous floodplain soils (Gothic, Colorado, USA). Combining metabolomics and -proteomics, we found a lower abundance of oxidative enzymes during flooding coincided with the accumulation of aromatic, high-molecular weight compounds, particularly in surface soils. In subsurface soils, we found that a lower oxidation state of carbon coincided with a greater abundance of chemically reduced, energetically less favorable low-molecular weight metabolites, irrespective of flooding condition. Our results suggest that seasonal flooding temporarily constrains oxidative depolymerization of larger, potentially plant-derived compounds in surface soils; in contrast, energetic constraints on microbial respiration persist in more reducing subsurface soils regardless of flooding. Our work underscores that the potential vulnerability of these distinct anaerobic carbon storage mechanisms to changing flooding dynamics should be considered, particularly as climate change shifts both the frequency and extent of flooding in floodplains globally.

Performance of Computer-Aided Detection and Quality of Bowel Preparation: A Comprehensive Analysis of Colonoscopy Outcomes.

BACKGROUND: Artificial intelligence (AI) has emerged as a promising tool for detecting and characterizing colorectal polyps during colonoscopy, offering potential enhancements in traditional colonoscopy procedures to improve outcomes in patients with inadequate bowel preparation. AIMS: This study aimed to assess the impact of an AI tool on computer-aided detection (CADe) assistance during colonoscopy in this population. METHODS: This case-control study utilized propensity score matching (PSM) for age, sex, race, and colonoscopy indication to analyze a database of patients who underwent colonoscopy at a single tertiary referral center between 2017 and 2023. Patients were excluded if the procedure was incomplete or aborted owing to poor preparation. The patients were categorized based on the use of AI during colonoscopy. Data on patient demographics and colonoscopy performance metrics were collected. Univariate and multivariate logistic regression models were used to compare the groups. RESULTS: After PSM patients with adequately prepped colonoscopies (n = 1466), the likelihood of detecting hyperplastic polyps (OR = 2.0, 95%CI 1.7-2.5, p < 0.001), adenomas (OR = 1.47, 95%CI 1.19-1.81, p < 0.001), and sessile serrated polyps (OR = 1.90, 95%CI 1.20-3.03, p = 0.007) significantly increased with the inclusion of CADe. In inadequately prepped patients (n = 160), CADe exhibited a more pronounced impact on the polyp detection rate (OR = 4.34, 95%CI 1.6-6.16, p = 0.049) and adenomas (OR = 2.9, 95%CI 2.20-8.57, p < 0.001), with a marginal increase in withdrawal and procedure times. CONCLUSION: This study highlights the significant improvement in detecting diminutive polyps (< 5 mm) and sessile polyps using CADe, although notably, this benefit was only seen in patients with adequate bowel preparation. In conclusion, the integration of AI in colonoscopy, driven by artificial intelligence, promises to significantly enhance lesion detection and diagnosis, revolutionize the procedure's effectiveness, and improve patient outcomes.

A qualitative study to understand the barriers and facilitators in smoking cessation practices among oncology health care practitioners in one health system.

INTRODUCTION: Despite the benefits of quitting smoking for those who have cancer, including improved health outcomes and reduced therapeutic toxicities, it is unclear how many people are supported in quit attempts during this time. Variations in the availability and provision of smoking cessation (SC) services are reported, with little understanding of the challenges and solutions. This co-designed study aimed to understand the perspectives of health care professionals (HCPs) working in oncology settings to engage in SC practices and identify recommendations for developing an SC pathway. METHODS: This was a qualitative study. Eighteen HCPs participated in semi-structured interviews from July 2021 to May 2022. We used thematic analysis approaches to code data and present four emergent themes and SC strategies at micro, meso and organizational levels. RESULTS: Four themes emerged specifically: 1) timing and knowledge, 2) building a relationship, 3) frequent asking with infrequent action, and 4) removing the barriers and tailoring the system. While HCPs discuss SC, there are variations in documentation and when conversations occur. Primarily, HCPs value the time to build therapeutic relationships with patients and thus may limit SC discussions in preference to treatment in clinical interactions. The role of structural barriers, including prescriptive authority for nurses, hinders active SC processes, as it is the lack of continuity and embedding of services supported by a clinical champion for SC. CONCLUSIONS: The study suggests re-evaluating the status quo in SC service, highlighting service gaps and suggesting opportunities at organizational levels to reduce structural barriers. IMPLICATIONS: Variations in smoking cessation services exist in designated cancer centres. The data from this study can be used to inform a real time health systems approach for SC services in oncology settings. Developing tailored smoking cessation services and interventions that are patient-centred and informed by their experiences are required. The data in this study suggests developing specialist education and training to upskill HCPs for equitable engagement if we are to meet EU and Moonshot goals for cancer reduction.

Patients' and Clinicians' Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews.

BACKGROUND: Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. OBJECTIVE: We aim to explore patients' and clinicians' perspectives of the utility and real-world application of PRMs to improve the management of CRS. METHODS: Focus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. RESULTS: Both clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. CONCLUSIONS: Findings from this study provide information on clinicians' and patients' perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081.

Smoking Cessation Support: A Marathon, Not a Sprint; The Perspectives of Cancer Patients Who Smoke.

OBJECTIVES: Despite the unfavorable outcomes associated with continued smoking, a substantial proportion of patients with cancer continue to smoke after diagnosis. However, limited use of smoking cessation (SC) interventions has been reported. This study explored the perceptions of patients with cancer who continue to smoke/recently quit regarding SC. DATA SOURCES: Semistructured phone/Zoom/Webex interviews were conducted with 25 participants attending four Irish cancer hospitals who were current smokers or had quit at/after their cancer diagnosis. Thematic analysis was used to analyze the data. CONCLUSION: A total of four key themes emerged: (1) Diagnosis was a shock and a cue to action. (2) Brief and variable SC support: most participants did not feel stigmatized and reported receiving verbal or written information from oncology healthcare providers (HCPs) on SC supports. However, use of SC services was limited and largely ineffective. Some participants reported that SC discussions occurred earlier in their treatment with limited/no discussion later. (3) Facilitators vs barriers: the presence or absence of willpower and motivation was perceived as important. Family and HCP support helped while stress hindered SC. (4) SC support is a "marathon," not a "sprint." Patients with cancer who continue to smoke or recently quit want a sustained, tailored, nonjudgmental approach to SC incorporating pharmacological and behavioral interventions that span hospital-/community-based settings. IMPLICATIONS FOR NURSING PRACTICE: While consultants have been identified as the key HCP to initiate the SC discussion, oncology nurses can support patients with cancer who smoke/recently quit by advocating for comprehensive SC services and by using positive messaging and encouragement.

Social determinants of health influencing the adherence to post-endoscopic mucosal resection surveillance.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a global health challenge, particularly in Alabama, where the incidence rates exceed national averages. This study investigated the factors influencing adherence to post-endoscopic mucosal resection (EMR) colonoscopies, focusing on travel distance and socioeconomic status. This study aimed to provide evidence-based insights to improve patient care in CRC management. METHODS: This retrospective study in a tertiary care referral center analyzed 465 patients who underwent EMR. The data included demographics, clinical details, and travel-related variables. Descriptive statistics, logistic regression, and spatial analysis were used to assess the factors affecting adherence. RESULTS: Of 465 patients, 36.6 % had adequate follow-up, 21.8 % had inadequate follow-up, and 41.6 % were lost to follow-up. Noteworthy demographic variations were observed, with median ages differing across adherence groups. Traveled distances showcased compelling insights, indicating a median distance of 22.2 miles for adequate follow-up, 15.7 miles for inadequate follow-up, and 31.6 miles for the lost-to-follow-up group (p<0.001). Longer travel distances were associated with better adherence. Longer travel distances from the hospital were associated with significantly lower odds of inadequate follow-up: 10-25 miles OR:0.29, 25-85 miles OR:0.35, and >80 miles OR:0.24 compared to the first quartile (<10 miles). Socioeconomic factors, particularly educational attainment, significantly influenced the follow-up rates. CONCLUSIONS: This study revealed suboptimal post-EMR follow-up rates and underscored the impact of travel distance and socioeconomic factors. Targeted interventions addressing distance-related barriers can enhance treatment adherence and ensure timely CRC surveillance after EMR. Further research is needed in diverse healthcare settings.

Specialist cancer hospital-based smoking cessation service provision in Ireland.

BACKGROUND: While much progress has been made in reducing tobacco use in many countries, both active and passive smoking remain challenges. The benefits of smoking cessation are universally recognized, and the hospital setting is an ideal setting where smokers can access smoking cessation services as hospital admission can be a cue to action. Consistent delivery of good quality smoking cessation care across health services is an important focus for reducing the harm of tobacco use, especially among continued smokers. AIMS: Our objective was to document the smoking cessation medication and support services provided by specialist adult cancer hospitals across Ireland, a country with a stated tobacco endgame goal. METHODS: A cross-sectional survey based on recent national clinical guidelines was used to determine smoking cessation care delivery across eight specialist adult cancer tertiary referral university hospitals and one specialist radiotherapy center. Survey responses were collected using Qualtrics, a secure online survey software tool. The data was grouped, anonymized, and analyzed in Microsoft Excel. RESULTS: All responding hospitals demonstrated either some level of smoking cessation information or a service available to patients. However, there is substantial variation in the type and level of smoking cessation information offered, making access to smoking cessation services inconsistent and inequitable. CONCLUSION: The recently launched National Clinical Guideline for smoking cessation provides the template for all hospitals to ensure health services are in a position to contribute to Ireland's tobacco endgame goal.

Resolving experimental biases in the interpretation of diffusion experiments with a user-friendly numerical reactive transport approach.

The reactive transport code CrunchClay was used to derive effective diffusion coefficients (De), clay porosities (ε), and adsorption distribution coefficients (KD) from through-diffusion data while considering accurately the influence of unavoidable experimental biases on the estimation of these diffusion parameters. These effects include the presence of filters holding the solid sample in place, the variations in concentration gradients across the diffusion cell due to sampling events, the impact of tubing/dead volumes on the estimation of diffusive fluxes and sample porosity, and the effects of O-ring-filter setups on the delivery of solutions to the clay packing. Doing so, the direct modeling of the measurements of (radio)tracer concentrations in reservoirs is more accurate than that of data converted directly into diffusive fluxes. While the above-mentioned effects have already been described individually in the literature, a consistent modeling approach addressing all these issues at the same time has never been described nor made easily available to the community. A graphical user interface, CrunchEase, was created, which supports the user by automating the creation of input files, the running of simulations, and the extraction and comparison of data and simulation results. While a classical model considering an effective diffusion coefficient, a porosity and a solid/solution distribution coefficient (De-ε-KD) may be implemented in any reactive transport code, the development of CrunchEase makes it easy to apply by experimentalists without a background in reactive transport modeling. CrunchEase makes it also possible to transition more easily from a De-ε-KD modeling approach to a state-of-the-art process-based understanding modeling approach using the full capabilities of CrunchClay, which include surface complexation modeling and a multi-porosity description of the clay packing with charged diffuse layers.

River thorium concentrations can record bedrock fracture processes including some triggered by distant seismic events.

Fractures are integral to the hydrology and geochemistry of watersheds, but our understanding of fracture dynamics is very limited because of the challenge of monitoring the subsurface. Here we provide evidence that long-term, high-frequency measurements of the river concentration of the ultra-trace element thorium (Th) can provide a signature of bedrock fracture processes spanning neighboring watersheds in Colorado. River Th concentrations show abrupt (subdaily) excursions and biexponential decay with approximately 1-day and 1-week time constants, concentration patterns that are distinct from all other solutes except beryllium and arsenic. The patterns are uncorrelated with daily precipitation records or seasonal trends in atmospheric deposition. Groundwater Th analyses are consistent with bedrock release and dilution upon mixing with river water. Most Th excursions have no seismic signatures that are detectable 50 km from the site, suggesting the Th concentrations can reveal aseismic fracture or fault events. We find, however, a weak statistical correlation between Th and seismic motion caused by distant earthquakes, possibly the first chemical signature of dynamic earthquake triggering, a phenomenon previously identified only through geophysical methods.

Gastrointestinal Hemorrhage With Gastritis and Pancolitis as the Sole Presentation for Granulomatosis With Polyangiitis Flare.

Granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis, is a rare small vessel vasculitis affecting mainly Whites. The prevalence of GPA in the United States is estimated to be 3 of 100,000 individuals. Classically, GPA affects upper airways, lungs, and kidneys, with the upper airways being the most common site. Occasionally, other organs affected by GPA include eyes, skin, joints, and the nervous system. The gastrointestinal system is rarely affected; however, some cases have been reported. In this case report, we present a patient with hemorrhagic gastritis and pancolitis consistent with GPA and discuss features from the literature of gastrointestinal manifestations in patients with GPA.

Systematic Review of Smoking Cessation Interventions for Smokers Diagnosed with Cancer.

The detrimental impact of smoking on health and wellbeing are irrefutable. Additionally, smoking is associated with the development of cancer, a reduction treatment outcomes and poorer health outcomes. Nevertheless, a significant number of people continue to smoke following a cancer diagnosis. Little is understood of the smoking cessation services provided to smokers with cancer or their engagement with them. This systematic review aimed to identify existing smoking cessation interventions for this cohort diagnosed with breast, head and neck, lung and cervical cancers (linked to risk). Systematic searches of Pubmed, Embase, Psych Info and CINAHL from 1 January 2015 to 15 December 2020 were conducted. Included studies examined the characteristics of smoking cessation interventions and impact on referrals and quit attempts. The impact on healthcare professionals was included if reported. Included studies were restricted to adults with a cancer diagnosis and published in English. No restriction was placed on study designs, and narrative data synthesis was conducted due to heterogeneity. A review protocol was registered on PROSPERO CRD 42020214204, and reporting adheres to PRISMA reporting guidelines. Data were screened, extracted in duplicate and an assessment of the quality of evidence undertaken using Mixed Methods Assessment Tool. 23 studies met the inclusion criteria, representing USA, Canada, England, Lebanon, Australia and including randomized controlled trials (9), observational studies (10), quality improvement (3), and one qualitative study. Hospital and cancer clinics [including a dental clinic] were the settings for all studies. 43% (10/23) of studies reported interventions for smokers diagnosed with head and neck cancer, 13% (3/23) for smokers diagnosed with lung cancer, one study provides evidence for breast cancer, and the remaining nine studies (39%) report on multiple cancers including the ones specified in this review. Methodological quality was variable. There were limited data to identify one optimal intervention for this cohort. Key elements included the timing and frequency of quit conversations, use of electronic records, pharmacotherapy including extended use of varenicline, increased counselling sessions and a service embedded in oncology departments. More studies are required to ensure tailored smoking cessation pathways are co-developed for smokers with a diagnosis of cancer to support this population.

Beaver dams overshadow climate extremes in controlling riparian hydrology and water quality.

Hydrologic extremes dominate chemical exports from riparian zones and dictate water quality in major river systems. Yet, changes in land use and ecosystem services alongside growing climate variability are altering hydrologic extremes and their coupled impacts on riverine water quality. In the western U.S., warming temperatures and intensified aridification are increasingly paired with the expanding range of the American beaver-and their dams, which transform hydrologic and biogeochemical cycles in riparian systems. Here, we show that beaver dams overshadow climatic hydrologic extremes in their effects on water residence time and oxygen and nitrogen fluxes in the riparian subsurface. In a mountainous watershed in Colorado, U.S.A., we find that the increase in riparian hydraulic gradients imposed by a beaver dam is 10.7-13.3 times greater than seasonal hydrologic extremes. The massive hydraulic gradient increases hyporheic nitrate removal by 44.2% relative to seasonal extremes alone. A drier, hotter climate in the western U.S. will further expand the range of beavers and magnify their impacts on watershed hydrology and biogeochemistry, illustrating that ecosystem feedbacks to climate change will alter water quality in river systems.

Building research capacity and culture: Exploring nurses' experience of implementing a nurse-led clinical trial.

AIM: To explore the experiences of a nursing team who implemented an international nurse-led clinical trial in practice and understand the facilitators to their involvement. BACKGROUND: The role and responsibilities of the clinical nurse are advancing to encompass research activity to help inform evidence-based practice. However, several personal and organisational challenges can inhibit nurses' capacity to implement and undertake research within clinical practice. METHODS: Three focus groups were conducted with members of a nursing team (N = 18). Thematic analysis was employed, and themes were identified and agreed upon by the research team. RESULTS: Five themes were identified: 'Previous experience of and attitudes to participation in clinical research', 'Decision-making regarding participation in the clinical trial', 'Facilitators of participation in the clinical trial', 'Challenges of research in nursing practice' and 'Future orientation towards research'. CONCLUSION: Through their experiences of implementing a nurse-led clinical trial within practice, nurses recognized a number of facilitators and challenges to their participation. The perceived relevance of the clinical trial to the nurses' practice, potential to improve patient care and appreciation of the nurse leader's expertise and understanding of their context were key motivators. Reciprocal trust with the nurse leader who was encouraging, motivating, supportive and accessible resulted in the engagement and commitment of the nursing team. IMPLICATIONS FOR NURSING MANAGEMENT: This paper offers a perspective that can inform senior nursing management teams when implementing and conducting evidence-based research amongst nursing teams and in doing so meet the needs of developing research capacity amongst clinical nurses.

Has the National Fall in Smoking Rates in Ireland Been Replicated in Cancer Patients? A 5-Year Report.

Smoking among cancer patients leads to poorer outcomes, yet many patients continue smoking. As part of a feasibility study of smoking cessation for cancer patients in Ireland, smoking rates were reviewed. Hospital Inpatient Enquiry (HIPE) data on the smoking status of discharges with a cancer diagnosis (overall, breast, lung, cervical and head and neck cancer) were used (2014-2018). During 2014-2017, current smoking increased for overall (10.5-11.7%) and lung cancer (24.7-27.2%), then decreased to 11.4% and 24.1%, respectively, in 2018. Current smoking increased for cervical during 2014-2018 (11-19.8%) and initially (2014-2016) for head and neck (3-12.7%) cancer, decreasing to 7.6% in 2018; breast cancer was stable at 6 ± 0.6%. These rates are lower than the Irish (23-20%) and European (29% (average)) general population. During 2014-2017, past smoking increased among overall (15.2-21%) and specific cancers, which was lower than the Irish general population (23-28%). Current smoking was highest among 50-59-year-olds (14-16%), which contrasts with the Irish general population (24-35 years at 32-28%). HIPE data are subject to potential duplicate episodes of care and under-documentation of smoking. However, trend analysis is useful, as these limitations should be stable. Rates remain high; therefore, robust documentation and smoking cessation referrals for cancer patients are important.

Production of hydrogen peroxide in an intra-meander hyporheic zone at East River, Colorado.

The traditionally held assumption that photo-dependent processes are the predominant source of H2O2 in natural waters has been recently questioned by an increrasing body of evidence showing the ubiquitiousness of H2O2 in dark water bodies and in groundwater. In this study, we conducted field measurement of H2O2 in an intra-meander hyporheic zone and in surface water at East River, CO. On-site detection using a sensitive chemiluminescence method suggests H2O2 concentrations in groundwater ranging from 6 nM (at the most reduced region) to ~ 80 nM (in a locally oxygen-rich area) along the intra-meander transect with a maxima of 186 nM detected in the surface water in an early afternoon, lagging the maximum solar irradiance by ∼ 1.5 h. Our results suggest that the dark profile of H2O2 in the hyporheic zone is closely correlated to local redox gradients, indicating that interactions between various redox sensitive elements could play an essential role. Due to its transient nature, the widespread presence of H2O2 in the hyporheic zone indicates the existence of a sustained balance between H2O2 production and consumption, which potentially involves a relatively rapid succession of various biogeochemically important processes (such as organic matter turnover, metal cycling and contaminant mobilization). More importantly, this study confirmed the occurrence of reactive oxygen species at a subsurface redox transition zone and further support our understanding of redox boundaries on reactive oxygen species generation and as key locations of biogeochemical activity.

Microbial Phosphorus Mobilization Strategies Across a Natural Nutrient Limitation Gradient and Evidence for Linkage With Iron Solubilization Traits.

Microorganisms have evolved several mechanisms to mobilize and mineralize occluded and insoluble phosphorus (P), thereby promoting plant growth in terrestrial ecosystems. However, the linkages between microbial P-solubilization traits and the preponderance of insoluble P in natural ecosystems are not well known. We tested the P solubilization traits of hundreds of culturable bacteria representative of the rhizosphere from a natural gradient where P concentration and bioavailability decline as soil becomes progressively more weathered. Aluminum, iron phosphate and organic P (phytate) were expected to dominate in more weathered soils. A defined cultivation medium with these chemical forms of P was used for isolation. A combination of soil chemical, spectroscopic analyses and 16S rRNA gene sequencing were used to understand the in situ ability for solubilization of these predominant forms of P. Locations with more occluded and organic P harbored the greatest abundance of P-mobilizing microorganisms, especially Burkholderiaceae (Caballeronia and Paraburkholderia spp.). Nearly all bacteria utilized aluminum phosphate, however fewer could subsist on iron phosphate (FePO4) or phytate. Microorganisms isolated from phytic acid were also most effective at solubilizing FePO4, suggesting that phytate solubilization may be linked to the ability to solubilize Fe. Significantly, we observed Fe to be co-located with P in organic patches in soil. Siderophore addition in lab experiments reinstated phytase mediated P-solubilization from Fe-phytate complexes. Taken together, these results indicate that metal-organic-P complex formation may limit enzymatic P solubilization from phytate in soil. Additionally, the linked traits of phytase and siderophore production were mostly restricted to specific clades within the Burkholderiaceae. We propose that Fe complexation of organic P (e.g., phytate) represents a major constraint on P turnover and availability in acidic soils, as only a limited subset of bacteria appear to possess the traits required to access this persistent pool of soil P.

Real time remote symptom monitoring during chemotherapy for cancer: European multicentre randomised controlled trial (eSMART).

OBJECTIVE: To evaluate effects of remote monitoring of adjuvant chemotherapy related side effects via the Advanced Symptom Management System (ASyMS) on symptom burden, quality of life, supportive care needs, anxiety, self-efficacy, and work limitations. DESIGN: Multicentre, repeated measures, parallel group, evaluator masked, stratified randomised controlled trial. SETTING: Twelve cancer centres in Austria, Greece, Norway, Republic of Ireland, and UK. PARTICIPANTS: 829 patients with non-metastatic breast cancer, colorectal cancer, Hodgkin's disease, or non-Hodgkin's lymphoma receiving first line adjuvant chemotherapy or chemotherapy for the first time in five years. INTERVENTION: Patients were randomised to ASyMS (intervention; n=415) or standard care (control; n=414) over six cycles of chemotherapy. MAIN OUTCOME MEASURES: The primary outcome was symptom burden (Memorial Symptom Assessment Scale; MSAS). Secondary outcomes were health related quality of life (Functional Assessment of Cancer Therapy-General; FACT-G), Supportive Care Needs Survey Short-Form (SCNS-SF34), State-Trait Anxiety Inventory-Revised (STAI-R), Communication and Attitudinal Self-Efficacy scale for cancer (CASE-Cancer), and work limitations questionnaire (WLQ). RESULTS: For the intervention group, symptom burden remained at pre-chemotherapy treatment levels, whereas controls reported an increase from cycle 1 onwards (least squares absolute mean difference -0.15, 95% confidence interval -0.19 to -0.12; P<0.001; Cohen's D effect size=0.5). Analysis of MSAS sub-domains indicated significant reductions in favour of ASyMS for global distress index (-0.21, -0.27 to -0.16; P<0.001), psychological symptoms (-0.16, -0.23 to -0.10; P<0.001), and physical symptoms (-0.21, -0.26 to -0.17; P<0.001). FACT-G scores were higher in the intervention group across all cycles (mean difference 4.06, 95% confidence interval 2.65 to 5.46; P<0.001), whereas mean scores for STAI-R trait (-1.15, -1.90 to -0.41; P=0.003) and STAI-R state anxiety (-1.13, -2.06 to -0.20; P=0.02) were lower. CASE-Cancer scores were higher in the intervention group (mean difference 0.81, 0.19 to 1.43; P=0.01), and most SCNS-SF34 domains were lower, including sexuality needs (-1.56, -3.11 to -0.01; P<0.05), patient care and support needs (-1.74, -3.31 to -0.16; P=0.03), and physical and daily living needs (-2.8, -5.0 to -0.6; P=0.01). Other SCNS-SF34 domains and WLQ were not significantly different. Safety of ASyMS was satisfactory. Neutropenic events were higher in the intervention group. CONCLUSIONS: Significant reduction in symptom burden supports the use of ASyMS for remote symptom monitoring in cancer care. A "medium" Cohen's effect size of 0.5 showed a sizable, positive clinical effect of ASyMS on patients' symptom experiences. Remote monitoring systems will be vital for future services, particularly with blended models of care delivery arising from the covid-19 pandemic. TRIAL REGISTRATION: Clinicaltrials.gov NCT02356081.

Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial.

BACKGROUND: Retrospective studies suggest that conditioning therapy with busulfan plus melphalan could result in longer progression-free survival compared with melphalan alone in patients with multiple myeloma undergoing autologous haemopoietic cell transplantation (auto-HCT). We aimed to test this hypothesis in a randomised trial. METHODS: The primary objective of the study was to compare progression-free survival with conditioning of busulfan plus melphalan with melphalan alone in patients with multiple myeloma. Patients with newly diagnosed multiple myeloma who were eligible for cell transplantation, aged 70 years or younger, with at least stable disease, were randomly assigned (1:1) to treatment. Patients received either busulfan plus melphalan, with a test dose of busulfan 32 mg/m2 followed by pharmacokinetically adjusted doses on days -7, -6, -5, and -4 to achieve a target daily area under the curve (AUC) of 5000 mmol-minute and melphalan 70 mg/m2 per day on days -2 and -1 (total melphalan dose 140 mg/m2), or a melphalan dose of 200 mg/m2 on day -2. Randomisation was performed via a Clinical Trial Conduct Website at the University of Texas MD Anderson Cancer Center. The accrual is complete and final results are presented here. The study is registered with ClinicalTrials.gov, number NCT01413178. FINDINGS: Between Oct 12, 2011, and March 22, 2017, 205 patients were assessed for eligibility and randomly assigned to treatment. The primary analysis of progression-free survival was measured in 202 patients who received treatment: 104 patients in the busulfan plus melphalan group and 98 patients in the melphalan alone group. 90 days after auto-HCT, 102 (98%) of 104 patients given busulfan plus melphalan and 95 (97%) of 98 patients given melphalan alone achieved partial response or better. The median follow-up in the busulfan plus melphalan group was 22·6 months (IQR 15·2-47·1) and 20·2 months (IQR 8·8-46·6) in the melphalan alone group. Median progression-free survival was 64·7 months (32·9-64·7) with busulfan plus melphalan versus 43·5 months (19·9-not estimated) with melphalan alone (hazard ratio 0·53 [95% CI 0·30-0·91]; p=0·022). There were no treatment-related deaths by day 100 in either group. Grade 2-3 mucositis was observed in 77 (74%) of 104 patients in the busulfan plus melphalan group versus 14 (14%) of 98 patients in the melphalan alone group. INTERPRETATION: These findings, if confirmed in other ongoing studies, suggest that busulfan plus melphalan could replace melphalan alone as the conditioning regimen for auto-HCT in patients with newly diagnosed myeloma. FUNDING: This study was funded in part by the National Institutes of Health (NIH) through MD Anderson's Cancer Center Support Grant (CA016672).

Adaptation and Implementation of a Mobile Phone-Based Remote Symptom Monitoring System for People With Cancer in Europe.

BACKGROUND: There has been an international shift in health care, which has seen an increasing focus and development of technological and personalized at-home interventions that aim to improve health outcomes and patient-clinician communication. However, there is a notable lack of empirical evidence describing the preparatory steps of adapting and implementing technology of this kind across multiple countries and clinical settings. OBJECTIVE: This study aimed to describe the steps undertaken in the preparation of a multinational, multicenter randomized controlled trial (RCT) to test a mobile phone-based remote symptom monitoring system, that is, Advanced Symptom Management System (ASyMS), designed to enhance management of chemotherapy toxicities among people with cancer receiving adjuvant chemotherapy versus standard cancer center care. METHODS: There were 13 cancer centers across 5 European countries (Austria, Greece, Ireland, Norway, and the United Kingdom). Multiple steps were undertaken, including a scoping review of empirical literature and clinical guidelines, translation and linguistic validation of study materials, development of standardized international care procedures, and the integration and evaluation of the technology within each cancer center. RESULTS: The ASyMS was successfully implemented and deployed in clinical practices across 5 European countries. The rigorous and simultaneous steps undertaken by the research team highlighted the strengths of the system in clinical practice, as well as the clinical and technical changes required to meet the diverse needs of its intended users within each country, before the commencement of the RCT. CONCLUSIONS: Adapting and implementing this multinational, multicenter system required close attention to diverse considerations and unique challenges primarily related to communication and clinical and technical issues. Success was dependent on collaborative and transparent communication among academics, the technology industry, translation partners, patients, and clinicians as well as a simultaneous and rigorous methodological approach within the 5 relevant countries.