Smartphone sensors for monitoring cancer-related Quality of Life: App design, EORTC QLQ-C30 mapping and feasibility study in healthy subjects

[EN] Quality of life (QoL) indicators are now being adopted as clinical outcomes in clinical trials on cancer treatments. Technology-free daily monitoring of patients is complicated, time-consuming and expensive due to the need for vast amounts of resources and personnel. The alternative method of using the patients¿ own phones could reduce the burden of continuous monitoring of cancer patients in clinical trials. This paper proposes monitoring the patients¿ QoL by gathering data from their own phones. We considered that the continuous multiparametric acquisition of movement, location, phone calls, conversations and data use could be employed to simultaneously monitor their physical, psychological, social and environmental aspects. An open access phone app was developed (Human Dynamics Reporting Service (HDRS)) to implement this approach. We here propose a novel mapping between the standardized QoL items for these patients, the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and define HDRS monitoring indicators. A pilot study with university volunteers verified the plausibility of detecting human activity indicators directly related to QoL.Funding for this study was provided by the authors' various departments, and partially by the CrowdHealth Project (Collective Wisdom Driving Public Health Policies (727560)) and the MTS4up project (DPI2016-80054-R).Asensio Cuesta, S.; Sánchez-García, Á.; Conejero, JA.; Sáez Silvestre, C.; Rivero-Rodriguez, A.; Garcia-Gomez, JM. (2019). Smartphone sensors for monitoring cancer-related Quality of Life: App design, EORTC QLQ-C30 mapping and feasibility study in healthy subjects. International Journal of Environmental research and Public Health. 16(3):1-18. https://doi.org/10.3390/ijerph16030461S118163Number of Smartphone Users Worldwide from 2014 to 2020 (in Billions)https://www.statista.com/statistics/330695/number-of-smartphone-users-worldwide/Mirkovic, J., Kaufman, D. R., & Ruland, C. M. (2014). Supporting Cancer Patients in Illness Management: Usability Evaluation of a Mobile App. JMIR mHealth and uHealth, 2(3), e33. doi:10.2196/mhealth.3359Xing Su, Hanghang Tong, & Ping Ji. (2014). Activity recognition with smartphone sensors. Tsinghua Science and Technology, 19(3), 235-249. doi:10.1109/tst.2014.6838194Schmitz Weiss, A. (2013). Exploring News Apps and Location-Based Services on the Smartphone. Journalism & Mass Communication Quarterly, 90(3), 435-456. doi:10.1177/1077699013493788Higgins, J. P. (2016). Smartphone Applications for Patients’ Health and Fitness. The American Journal of Medicine, 129(1), 11-19. doi:10.1016/j.amjmed.2015.05.038Rivenson, Y., Ceylan Koydemir, H., Wang, H., Wei, Z., Ren, Z., Günaydın, H., … Ozcan, A. (2018). Deep Learning Enhanced Mobile-Phone Microscopy. ACS Photonics, 5(6), 2354-2364. doi:10.1021/acsphotonics.8b00146Priye, A., Ball, C. S., & Meagher, R. J. (2018). Colorimetric-Luminance Readout for Quantitative Analysis of Fluorescence Signals with a Smartphone CMOS Sensor. Analytical Chemistry, 90(21), 12385-12389. doi:10.1021/acs.analchem.8b03521Measuring Quality of Life for Cancer Patients: Where Are We Today and Where Are We Headed Tomorrow?http://blog.mdsol.com/measuring-quality-of-life-for-cancer-patients-where-are-we-today-and-where-are-we-headed-tomorrow/Zulueta, J., Piscitello, A., Rasic, M., Easter, R., Babu, P., Langenecker, S. A., … Leow, A. (2018). Predicting Mood Disturbance Severity with Mobile Phone Keystroke Metadata: A BiAffect Digital Phenotyping Study. Journal of Medical Internet Research, 20(7), e241. doi:10.2196/jmir.9775Caruso, R., GiuliaNanni, M., Riba, M. B., Sabato, S., & Grassi, L. (2017). Depressive Spectrum Disorders in Cancer: Diagnostic Issues and Intervention. A Critical Review. Current Psychiatry Reports, 19(6). doi:10.1007/s11920-017-0785-7THE WHOQOL GROUP. (1998). Development of the World Health Organization WHOQOL-BREF Quality of Life Assessment. Psychological Medicine, 28(3), 551-558. doi:10.1017/s0033291798006667Basic Issues Concerning Health-Related Quality of Life. (2017). Central European Journal of Urology, 70(2). doi:10.5173/ceju.2017.923Sloan, J. A. (2011). Metrics to Assess Quality of Life After Management of Early-Stage Lung Cancer. The Cancer Journal, 17(1), 63-67. doi:10.1097/ppo.0b013e31820e15dcBordoni, R., Ciardiello, F., von Pawel, J., Cortinovis, D., Karagiannis, T., Ballinger, M., … Rittmeyer, A. (2018). Patient-Reported Outcomes in OAK: A Phase III Study of Atezolizumab Versus Docetaxel in Advanced Non–Small-cell Lung Cancer. Clinical Lung Cancer, 19(5), 441-449.e4. doi:10.1016/j.cllc.2018.05.011Hartkopf, A. D., Graf, J., Simoes, E., Keilmann, L., Sickenberger, N., Gass, P., … Wallwiener, M. (2017). Electronic-Based Patient-Reported Outcomes: Willingness, Needs, and Barriers in Adjuvant and Metastatic Breast Cancer Patients. JMIR Cancer, 3(2), e11. doi:10.2196/cancer.6996Wallwiener, M., Matthies, L., Simoes, E., Keilmann, L., Hartkopf, A. D., Sokolov, A. N., … Brucker, S. Y. (2017). Reliability of an e-PRO Tool of EORTC QLQ-C30 for Measurement of Health-Related Quality of Life in Patients With Breast Cancer: Prospective Randomized Trial. Journal of Medical Internet Research, 19(9), e322. doi:10.2196/jmir.8210Gresham, G., Hendifar, A. E., Spiegel, B., Neeman, E., Tuli, R., Rimel, B. J., … Shinde, A. M. (2018). Wearable activity monitors to assess performance status and predict clinical outcomes in advanced cancer patients. npj Digital Medicine, 1(1). doi:10.1038/s41746-018-0032-6BOHANNON, R. W. (1997). Comfortable and maximum walking speed of adults aged 20—79 years: reference values and determinants. Age and Ageing, 26(1), 15-19. doi:10.1093/ageing/26.1.15Pérez-García, V. M., Fitzpatrick, S., Pérez-Romasanta, L. A., Pesic, M., Schucht, P., Arana, E., & Sánchez-Gómez, P. (2016). Applied mathematics and nonlinear sciences in the war on cancer. Applied Mathematics and Nonlinear Sciences, 1(2), 423-436. doi:10.21042/amns.2016.2.00036Shin, W., Song, S., Jung, S.-Y., Lee, E., Kim, Z., Moon, H.-G., … Lee, J. E. (2017). The association between physical activity and health-related quality of life among breast cancer survivors. Health and Quality of Life Outcomes, 15(1). doi:10.1186/s12955-017-0706-9Wearable Fitness Monitors Useful in Cancer Treatment, Study Findswww.sciencedaily.com/releases/2018/05/180501130856.htmBade, B. C., Brooks, M. C., Nietert, S. B., Ulmer, A., Thomas, D. D., Nietert, P. J., … Silvestri, G. A. (2016). Assessing the Correlation Between Physical Activity and Quality of Life in Advanced Lung Cancer. Integrative Cancer Therapies, 17(1), 73-79. doi:10.1177/1534735416684016Fortner, B. V., Stepanski, E. J., Wang, S. C., Kasprowicz, S., & Durrence, H. H. (2002). Sleep and Quality of Life in Breast Cancer Patients. Journal of Pain and Symptom Management, 24(5), 471-480. doi:10.1016/s0885-3924(02)00500-6Mishra, S. I., Scherer, R. W., Snyder, C., Geigle, P., & Gotay, C. (2014). Are Exercise Programs Effective for Improving Health-Related Quality of Life Among Cancer Survivors? A Systematic Review and Meta-Analysis. Oncology Nursing Forum, 41(6), E326-E342. doi:10.1188/14.onf.e326-e342Ratcliff, C. G., Lam, C. Y., Arun, B., Valero, V., & Cohen, L. (2014). Ecological momentary assessment of sleep, symptoms, and mood during chemotherapy for breast cancer. Psycho-Oncology, 23(11), 1220-1228. doi:10.1002/pon.3525Cox, S. M., Lane, A., & Volchenboum, S. L. (2018). Use of Wearable, Mobile, and Sensor Technology in Cancer Clinical Trials. JCO Clinical Cancer Informatics, (2), 1-11. doi:10.1200/cci.17.00147Brown, W., Yen, P.-Y., Rojas, M., & Schnall, R. (2013). Assessment of the Health IT Usability Evaluation Model (Health-ITUEM) for evaluating mobile health (mHealth) technology. Journal of Biomedical Informatics, 46(6), 1080-1087. doi:10.1016/j.jbi.2013.08.001Darlow, S., & Wen, K.-Y. (2016). Development testing of mobile health interventions for cancer patient self-management: A review. Health Informatics Journal, 22(3), 633-650. doi:10.1177/1460458215577994Martin Sanchez, F., Gray, K., Bellazzi, R., & Lopez-Campos, G. (2014). Exposome informatics: considerations for the design of future biomedical research information systems. Journal of the American Medical Informatics Association, 21(3), 386-390. doi:10.1136/amiajnl-2013-001772Kim, H. H., Lee, S. Y., Baik, S. Y., & Kim, J. H. (2015). MELLO: Medical lifelog ontology for data terms from self-tracking and lifelog devices. International Journal of Medical Informatics, 84(12), 1099-1110. doi:10.1016/j.ijmedinf.2015.08.005Kessel, K. A., Vogel, M. M., Alles, A., Dobiasch, S., Fischer, H., & Combs, S. E. (2018). Mobile App Delivery of the EORTC QLQ-C30 Questionnaire to Assess Health-Related Quality of Life in Oncological Patients: Usability Study. JMIR mHealth and uHealth, 6(2), e45. doi:10.2196/mhealth.9486Elsbernd, A., Hjerming, M., Visler, C., Hjalgrim, L. L., Niemann, C. U., Boisen, K., & Pappot, H. (2018). Cocreated Smartphone App to Improve the Quality of Life of Adolescents and Young Adults with Cancer (Kræftværket): Protocol for a Quantitative and Qualitative Evaluation. JMIR Research Protocols, 7(5), e10098. doi:10.2196/1009

Evaluation of the role of the Bvg intermediate phase in Bordetella pertussis during experimental respiratory infection

The BvgAS system of Bordetella pertussis was traditionally considered to mediate a transition between two phenotypic phases (Bvg(+) and Bvg(-)) in response to environmental signals. We characterized a third state, the intermediate (Bvg(i)) phase, which can be induced by introducing a 1-bp substitution into bvgS (the bvgS-I1 mutation) or by growing B. pertussis under conditions intermediate between those leading to the Bvg(+) and Bvg(-) phases. Like B. bronchiseptica, B. pertussis displays in its Bvg(i) phase a characteristic colony morphology and hemolytic activity and expresses a Bvg(i)-phase-specific polypeptide called BipA, whose synthesis is regulated by bvgAS at the transcriptional level. Based on our results, we hypothesize that the Bvg(i) phase of B. pertussis may be involved in facilitating transmission between hosts. Thus, a B. pertussis mutant carrying the bvgS-I1 mutation (GMT1i) persisted at wild-type levels only in the upper murine respiratory tract. Interestingly, a bipA deletion derivative of GMT1i displayed a reduced ability to colonize the nasal cavity of mice compared with GMT1i. However, in experimental mixed infections GMT1i expressing the Bvg(i) phase could establish an initial colonization in the nose and trachea of mice as efficiently as GMT1, but the wild-type strain outcompeted GMT1i at a later time point at all sites of the respiratory tract, suggesting that the Bvg(i) phase does not serve as a phenotypic phase specialized in colonization. Finally, even though B. pertussis expresses in vitro the Bvg(i) phase at the human nasal temperature, anti-BipA antibodies were undetectable in a large collection of sera from pertussis patients

Cavitary pneumonia in an AIDS patient caused by an unusual Bordetella bronchiseptica variant producing reduced amounts of pertactin and other major antigens

Although Bordetella bronchiseptica can infect and colonize immunocompromised humans, its role as a primary pathogen in pneumonia and other respiratory processes affecting those patients remains controversial. A case of cavitary pneumonia caused by B. bronchiseptica in an AIDS patient is presented, and the basis of the seemingly enhanced pathogenic potential of this isolate (designated 814) is investigated. B. bronchiseptica was the only microorganism recovered from sputum, bronchoalveolar lavage fluid, and samples taken through the protected brush catheter. Unlike previous work reporting the involvement of B. bronchiseptica in cases of pneumonia, antibiotic treatment selected on the basis of in vitro antibacterial activity resulted in clearance of the infection and resolution of the pulmonary infiltrate. Although isolate 814 produced reduced amounts of several major antigens including at least one Bvg-activated factor (pertactin), the molecular basis of this deficiency was found to be BvgAS independent since the defect persisted after the bvgAS locus of isolate 814 was replaced with a wild-type bvgAS allele. Despite its prominent phenotype, isolate 814 displayed only a modest yet a significant deficiency in its ability to colonize the respiratory tracts of immunocompetent rats at an early time point. Interestingly, the antibody response elicited by isolate 814 in these animals was almost undetectable. We propose that isolate 814 may be more virulent in immunocompromised patients due, at least in part, to its innate ability to produce low amounts of immunogenic factors which may be required at only normal levels for the interaction of this pathogen with its immunocompetent natural hosts

A synthetic peptide from transforming growth factor beta type III receptor inhibits liver fibrogenesis in rats with carbon tetrachloride liver injury

Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine, which displays potent profibrogenic effects and is highly expressed in fibrotic livers. For this reason, development of TGF-B1 inhibitors might be of great importance to control liver fibrogenesis as well as other undesired side effects due to this cytokine. Potential peptide inhibitors of TGF-beta1 (derived from TGF-beta1 and from its type III receptor) were tested in vitro and in vivo using different assays. Peptides P11 and P12, derived from TGF-beta1, and P54 and P144, derived from its type III receptor, prevented TGF-beta1-dependent inhibition of MV1Lu proliferation in vitro and markedly reduced binding of TGF-beta1 to its receptors. P144 blocked TGF-beta1-dependent stimulation of a reporter gene under the control of human alpha2(I) collagen promoter. Intraperitoneal administration of P144 also showed potent antifibrogenic activity in vivo in the liver of rats receiving CCl4. These rats also showed a significant decrease in the number of activated hepatic stellate cells as compared with those treated with saline only. These results suggest that short synthetic peptides derived from TGF-beta1 type III receptor may be of value in reducing liver fibrosis in chronic liver injury

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

Opposite cannabis-cognition associations in psychotic patients depending on family history

The objective of this study is to investigate cognitive performance in a first-episode psychosis sample, when stratifying the interaction by cannabis use and familial or non-familial psychosis. Hierarchical-regression models were used to analyse this association in a sample of 268 first-episode psychosis patients and 237 controls. We found that cannabis use was associated with worse working memory, regardless of family history. However, cannabis use was clearly associated with worse cognitive performance in patients with no family history of psychosis, in cognitive domains including verbal memory, executive function and global cognitive index, whereas cannabis users with a family history of psychosis performed better in these domains. The main finding of the study is that there is an interaction between cannabis use and a family history of psychosis in the areas of verbal memory, executive function and global cognition: that is, cannabis use is associated with a better performance in patients with a family history of psychosis and a worse performance in those with no family history of psychosis. In order to confirm this hypothesis, future research should explore the actual expression of the endocannabinoid system in patients with and without a family history of psychosis

Greening of the brown-dwarf desert EPIC 212036875b: a 51 M-J object in a 5-day orbit around an F7V star

Context. Although more than 2000 brown dwarfs have been detected to date, mainly from direct imaging, their characterisation is difficult due to their faintness and model-dependent results. In the case of transiting brown dwarfs, however, it is possible to make direct high-precision observations. Aims. Our aim is to investigate the nature and formation of brown dwarfs by adding a new well-characterised object, in terms of its mass, radius and bulk density, to the currently small sample of less than 20 transiting brown dwarfs. Methods. One brown dwarf candidate was found by the KESPRINT consortium when searching for exoplanets in the K2 space mission Campaign 16 field. We combined the K2 photometric data with a series of multicolour photometric observations, imaging, and radial velocity measurements to rule out false positive scenarios and to determine the fundamental properties of the system. Results. We report the discovery and characterisation of a transiting brown dwarf in a 5.17-day eccentric orbit around the slightly evolved F7V star EPIC 212036875. We find a stellar mass of 1.15 +/- 0.08 M-circle dot, a stellar radius of 1.41 +/- 0.05 R-circle dot, and an age of 5.1 +/- 0.9 Gyr. The mass and radius of the companion brown dwarf are 51 +/- 2 M-J and 0.83 +/- 0.03 R-J, respectively, corresponding to a mean density of 108(-13)(+15) g cm(-3). Conclusions. EPIC 212036875 b is a rare object that resides in the brown-dwarf desert. In the mass-density diagram for planets, brown dwarfs, and stars, we find that all giant planets and brown dwarfs follow the same trend from similar to 0.3 M-J to the turn-over to hydrogen burning stars at similar to 73 M-J. EPIC 212036875 b falls close to the theoretical model for mature H/He dominated objects in this diagram as determined by interior structure models. We argue that EPIC 212036875 b formed via gravitational disc instabilities in the outer part of the disc, followed by a quick migration. Orbital tidal circularisation may have started early in its history for a brief period when the brown dwarf\u27s radius was larger. The lack of spin-orbit synchronisation points to a weak stellar dissipation parameter (Q(star)\u27 greater than or similar to 10(8)), which implies a circularisation timescale of greater than or similar to 23 Gyr, or suggests an interaction between the magnetic and tidal forces of the star and the brown dwarf

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Background Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Study Design Prospective multinational cohort. Setting & Participants 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Predictors Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. Outcomes All-cause and cardiovascular mortality at 12 months after dental assessment. Measurements Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. Results During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Limitations Convenience sample of clinics. Conclusions In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival