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This article offers community partner perspectives on the National Science Foundation–funded Broader Impacts (BI) Toolkit, a new digital tool researchers can use to improve the societal relevance of their research. Partners suggest three ways the toolkit could be improved moving forward, underscoring the importance of relationship building to any BI activity.

BackgroundThe primary objective of this study was to examine the feasibility of recruitment, retention, and delivery of biomarker feedback among men partaking in Shape Up, a physical activity for health programme. Secondarily, it explored the potential effects of biomarker feedback on participants' adherence and motivation levels.MethodsIn this two-arm non-randomised pilot study, 46 men (mean±SD age 46.0±8.6 years) participating in the 12-week Shape Up programme were assigned to a control group or biomarker feedback group. Biomarker feedback consisted of 3 blood test panels: at baseline, 12 weeks, and 24 weeks (follow-up), each with a doctor's report. Both groups completed questionnaires (Short Active Lives Survey [SALS], Treatment Self-Regulation Questionnaire [TSRQ], and EQ-5D-5L) to gauge levels of motivation and engagement. The mean difference was calculated between baseline and programme end. Recruitment, retention, and attendance rates were determined.ResultsMean recruitment (approach-to-consent), retention, and attendance rates were 96.3%, 92.3%, and 83.7% in the control group, and 85.2%, 86.2%, and 81.5% in the biomarker feedback group, respectively. Of biomarker feedback group participants, 86.4% attended their 12-week blood test and 45.5% attended their follow-up blood test. The mean 12-week differences (95% CI) for the control group and biomarker feedback group were 138.1 (2.7, 273.5) and 467.3 (249.4, 685.2) for active minutes per week, 0.2 (-0.8, 1.2) and 0.4 (0.0, 0.8) for autonomous TSRQ domains, 0.2 (-0.3, 0.8) and 0.8 (0.1, 1.4) for controlled TSRQ domains, and 19 (12.7, 26.5) and 27.2 (19.8, 34.6) for EQ-5D-5L scores, respectively.ConclusionBiomarker feedback was well-received by participants and deemed feasible, with high recruitment and retention rates for the duration of the 12-week programme. Biomarker feedback may affect aspects of motivation but did not appear to influence adherence to the programme. Biomarker data may provide additional evidence of programme efficacy. Important design considerations are provided for definitive larger-scale trials.

Abstract Digital technologies such as smartphones are transforming the way scientists conduct biomedical research. Several remotely conducted studies have recruited thousands of participants over a span of a few months allowing researchers to collect real-world data at scale and at a fraction of the cost of traditional research. Unfortunately, remote studies have been hampered by substantial participant attrition, calling into question the representativeness of the collected data including generalizability of outcomes. We report the findings regarding recruitment and retention from eight remote digital health studies conducted between 2014–2019 that provided individual-level study-app usage data from more than 100,000 participants completing nearly 3.5 million remote health evaluations over cumulative participation of 850,000 days. Median participant retention across eight studies varied widely from 2–26 days (median across all studies = 5.5 days). Survival analysis revealed several factors significantly associated with increase in participant retention time, including (i) referral by a clinician to the study (increase of 40 days in median retention time); (ii) compensation for participation (increase of 22 days, 1 study); (iii) having the clinical condition of interest in the study (increase of 7 days compared with controls); and (iv) older age (increase of 4 days). Additionally, four distinct patterns of daily app usage behavior were identified by unsupervised clustering, which were also associated with participant demographics. Most studies were not able to recruit a sample that was representative of the race/ethnicity or geographical diversity of the US. Together these findings can help inform recruitment and retention strategies to enable equitable participation of populations in future digital health research.

IntroductionNitrate supplementation in the form of beetroot juice (BRJ) ingestion has been shown to improve exercise tolerance during acute hypoxia, but its effect on exercise physiology remains unstudied during sustained terrestrial high altitude exposure. We hypothesized that performing exercise at high altitude would lower circulating nitrate and nitrite levels and that BRJ ingestion would reverse this phenomenon while concomitantly improving key determinants of aerobic exercise performance.MethodsTwenty seven healthy volunteers (21 male) underwent a series of exercise tests at sea level (SL, London, 75 m) and again after 5–8 days at high altitude (HA, Capanna Regina Margherita or “Margherita Hut,” 4,559 m). Using a double-blind protocol, participants were randomized to consume a beetroot/fruit juice beverage (three doses per day) with high levels of nitrate (∼0.18 mmol/kg/day) or a nitrate-depleted placebo (∼11.5 μmoles/kg/day) control drink, from 3 days prior to the exercise trials until completion. Submaximal constant work rate cycle tests were performed to determine exercise efficiency and a maximal incremental ramp exercise test was undertaken to measure aerobic capacity, using breath-by-breath pulmonary gas exchange measurements throughout. Concentrations of nitrate, nitrite and nitrosation products were quantified in plasma samples collected at 5 timepoints during the constant work rate tests. Linear mixed modeling was used to analyze data.ResultsAt both SL and HA, plasma nitrate concentrations were elevated in the nitrate supplementation group compared to placebo (P < 0.001) but did not change throughout increasing exercise work rate. Delta exercise efficiency was not altered by altitude exposure (P = 0.072) or nitrate supplementation (P = 0.836). V̇O2peak decreased by 24% at high altitude (P < 0.001) and was lower in the nitrate-supplemented group at both sea level and high altitude compared to placebo (P = 0.041). Dietary nitrate supplementation did not alter other peak exercise variables or oxygen consumption at anaerobic threshold. Circulating nitrite and S-nitrosothiol levels unexpectedly rose in a few individuals right after cessation of exercise at high altitude.ConclusionWhilst regularly consumed during an 8 days expedition to terrestrial high altitude, nitrate supplementation did not alter exercise efficiency and other exercise physiological variables, except decreasing V̇O2peak. These results and those of others question the practical utility of BRJ consumption during prolonged altitude exposure.

Abstract Aims Limited data are available regarding the ability of sacubitril/valsartan to provide clinically meaningful health‐related quality of life (HRQoL) improvements among individuals with heart failure (HF). Objective measurement of physical activity and sleep using actigraphy can provide insight into daily functioning and HRQoL. Methods and results We designed an 18 week, multicenter, randomized, double‐blind, double‐dummy, parallel‐group study to objectively assess changes in function and HRQoL directly after initiating sacubitril/valsartan vs. enalapril in participants with HF in their home environments. A total of 136 outpatient, ambulatory participants with New York Heart Association Class II or III HF with reduced ejection fraction (HFrEF) will be included in the study. Patients will undergo a 2 week baseline observational phase (continuing current HF treatment); data from the second week of this phase will be the baseline value for comparison with those of subsequent periods. Patients will then enter an 8 week blinded‐treatment phase (randomly assigned 1:1 to sacubitril/valsartan or enalapril), followed by an 8 week open‐label extension phase (treatment with only sacubitril/valsartan). The primary efficacy endpoint is the change in mean activity counts during the most active 30 min of the participant's day between baseline and the final randomized treatment phase measurement. Secondary endpoints include the change in mean sleep activity during the randomized and open‐label phases; questionnaires will also assess HRQoL measures. Rather than analysing pooled actigraphy data, the researchers are considering each participant to be acting as his or her own control. Conclusions This will be the first study to assess the effects of sacubitril/valsartan on objective measures of sleep and activity in individuals with HFrEF within the context of their daily lives. Wearable accelerometer devices will be used to gain insight into how the medication affects physical activity and sleep.

Abstract Patients with axial spondyloarthritis (axSpA) frequently report pain, stiffness, fatigue, and sleep problems, which may lead to impaired physical activity. The majority of reported-on measures evaluating physical activity and sleep disturbance in axSpA are self-reported questionnaires, which can be impacted by patient recall (reporting bias). One objective measure, polysomnography, has been employed to evaluate sleep in patients with axSpA; however, it is an intrusive measure and cannot be used over the long term. More convenient objective measures are therefore needed to allow for the long-term assessment of both sleep and physical activity in patients’ daily lives. Wearable technology that utilizes actigraphy is increasingly being used for the objective measurement of physical activity and sleep in various therapy areas, as it is unintrusive and suitable for continuous tracking to allow longitudinal assessment. Actigraphy characterizes sleep disruption as restless movement while sleeping, which is particularly useful when studying conditions such as axSpA in which chronic pain and discomfort due to stiffness may be evident. Studies have also shown that actigraphy can effectively assess the impact of disease on physical activity. More research is needed to establish the usefulness of objective monitoring of sleep and physical activity specifically in axSpA patients over time. This review summarizes the current perspectives on physical activity and sleep quality in patients with axSpA, and the possible role of actigraphy in the future to more accurately evaluate the impact of treatment interventions on sleep and physical activity in axSpA. Funding: Novartis Pharmaceuticals Corporation. Plain Language Summary: Plain language summary available for this article.

Despite the risks associated with hypnotics and their recent increased use in Saudi Arabia, there are no specific national guidelines for using these medicines to treat insomnia nor are there any data on how these medicines are currently prescribed. There is the potential, however, that some physicians might be adhering to the United States guidelines. The current audit study was aimed to assess the current practice in treating insomnia with hypnotics in Saudi Arabia, and to evaluate its agreement with the US guidelines. The audit was conducted using data collected between April 2012 and March 2017 at King Fahad Central Hospital (KFCH; Jazan), of patients who were either prescribed benzodiazepines (BZDs) or Z-drugs or diagnosed with insomnia. The audit criteria followed two US guidelines for the management of insomnia in adults. Data included documented diagnosis, use of CBT-I (Cognitive Behavioral Therapy for Insomnia), use of BZDs and Z-drugs including treatment regimen, and whether physicians prescribed anti-histamines for insomnia. The data were analyzed using STATA 14 after transcription to a MS XL file. Of the 504 records reviewed, 379 patients (75%) were prescribed BZDs or Z-drugs; only 182 (48%) of them had clearly documented indications for their use. Three hundred and seven patients (60%) were diagnosed with insomnia; none of them received CBT-I as initial treatment. No patients on long-term use of hypnotics were reviewed by their physicians after they began using the medication. More than 43% of patients were prescribed anti-histamines for insomnia. No records met all (or even six) of the seven criteria. KFCH physicians do not follow US guidelines. Therefore, the Ministry of Health (MOH) should improve its administrative systems including documentation, and instead of using international guidelines that are seldom followed, physicians should be trained in prescribing hypnotics and national guidelines need to be developed.

Purpose: To increase access of underserved/health disparities communities to National Cancer Institute (NCI) clinical trials, the Radiation Research Program (RRP) piloted a unique model - the Cancer Disparities Research Partnership (CDRP) program. CDRP targeted community hospitals with a limited past NCI funding history and provided funding to establish the infrastructure for their clinical research program.Methods: Initially, 5-year planning phase funding was awarded to six CDRP institutions through a cooperative agreement (U56). Five were subsequently eligible to compete for 5-year implementation phase (U54) funding and three received a second award. Additionally, the NCI Center to Reduce Cancer Health Disparities supported their U56 Patient Navigation programs.Results: Community-based hospitals with little or no clinical trials experience required at least a year to develop the infrastructure and establish community outreach/education and Patient Navigation programs before accrual to clinical trials could begin. Once established, CDRP sites increased their yearly patient accrual mainly to NCI-sponsored cooperative group trials (~60%) and Principal Investigator (PI)/mentor-initiated trials (~30%). The total number of patients accrued on all types of trials was 2,371, while 5,147 patients received navigation services. Conclusions: Despite a historical gap in participation in clinical cancer research, underserved communities are willing/eager to participate. Since a limited number of cooperative group trials address locally advanced diseases seen in health disparities populations, this shortcoming needs to be rectified. Sustainability for these programs remains a challenge. Addressing these gaps through research and public health mechanisms may have an important impact on their health, scientific progress and efforts to increase diversity in NCI clinical trials.

Purpose: To identify sequence variants of the ataxia telangiectasia mutated (ATM) gene and establish their prevalence rate among American Indian (AI) as compared with non-AI cancer patients. Materials and Methods: DNA was isolated from blood samples collected from 100 AI and 100 non-AI cancer patients undergoing radiation therapy, and a blinded assessment of the ATM sequence was conducted. Quantitative PCR assessment of copy number for each exon was also performed. The main outcome measure was the prevalence of ATM variants in the two patient populations. Results: No statistically significant differences for total prevalence of ATM variants among AI and non-AI patients were found. Of the 25 variants identified, five variants had a prevalence of >2%, of which 4 occurred at a rate of >5% in one or both groups. The prevalence of these four variants could meaningfully be compared between the two groups. The only statistically significant difference among the groups was the c.4138C>T variant which is predicted not to affect protein function, seen in 8% of AI versus 0% of non-AI patients (P=0.007). No exonic copy number changes were found in these patients. Conclusions: This study is the first to determine the prevalence of ATM variants in AIs.

Purpose/Objective(s): American Indians (AIs) present with more advanced stages of cancer and, therefore, suffer from higher cancer mortality rates compared to non-AIs. Under the National Cancer Institute Cancer Disparities Research Partnership Program (CDRP), we have been researching methods of improving cancer treatment and outcomes since 2002, for AIs in Western South Dakota, through the Walking Forward (WF) Program.Materials/Methods: This program consists of a) a culturally-tailored patient navigation program that facilitated access to innovative clinical trials in conjunction with a comprehensive educational program encouraging screening and early detection, b), surveys to evaluate barriers to access c) clinical trials focusing on reducing treatment length to facilitate enhanced participation using brachytherapy and intensity modulated radiotherapy (IMRT) for breast and prostate cancer, as AIs live a median of 140 miles from the cancer center, and d) a molecular study (ATM - Ataxia telangectasia mutation) to address whether there is a specific profile that increases toxicity risks. Results: We describe the design and implementation of this program, summary of previously published results, and ongoing research to influence stage at presentation. Some of the critical outcomes include the successful implementation of a community based research program, development of trust within tribal communities, identification of barriers, analysis of nearly 400 navigated cancer patients, clinical trial accrual rate of 10%, and total enrollment of nearly 2,500 AIs on WF research studies. Conclusions: This NCI funded pilot program has achieved some initial measures of success. A research infrastructure has been created in a community setting to address new research questions and interventions. Efforts underway to promote cancer education and screening are presented, as well as applications of the lessons learned to other health disparity populations.

This paper introduces and uses Lakatos' idea of research programmes to summarise and critically evaluate academic discourse towards knowledge capital theory. The analysis uses rational reconstruction to formulate the components of the hardcore and protective belt of knowledge capital theory. By critically surveying the literature, it challenges the validity of the claims made by Erik Hanushek, Ludger Woessmann and the OECD that there is a causal link between cognitive development and economic growth. It concludes by stating that knowledge capital theory in its current form is degenerate and should be considered a high-risk research programme and that more sophisticated theories are required to be developed to explain current phenomena.