Perioperative telemonitoring of older adults with cancer:Can we connect them all?

OBJECTIVES: Although the increasing cancer incidence in older patients is widely recognised, older patients remain underrepresented in clinical cancer trials and eHealth studies. The aim of this research is to identify technological and patient-related barriers to inclusion of this population in a clinical eHealth study. MATERIAL AND METHODS: This is a retrospective analysis of a prospective cohort study with older patients (≥ 65 years) undergoing cancer-related surgery, who were identified for a perioperative telemonitoring study. Reasons for ineligibility and refusal had been prospectively registered. Characteristics and postoperative outcomes were compared between participants and non-participants. RESULTS: Between May 2018 and March 2020, 151 patients were assessed for eligibility, resulting in 65 participants and 86 non-participants. The main reason for ineligibility was lack of internet access at home (n = 16), while main reasons for refusal were perceived high mental burden (n = 46) and insufficient digital skills (n = 12). Compared with participants, non-participants were significantly older (mean age 75 vs. 73, p = 0.01); more often female (64% vs. 35%, p = 0.00), unmarried (42% vs. 8%, p = 0.01) living alone (38% vs. 19%, p = 0.02); had a higher ASA classification (43% vs. 19%, p = 0.00); often had polypharmacy (67% vs. 43%, p = 0.00); and were more often discharged to skilled nursing facilities (0% vs. 15%, p = 0.00). CONCLUSION: Our results confirm the underrepresentation of older female patients with little support from a partner and higher comorbidity. We should be aware of technological and patient-related barriers to including older adults with cancer, in order to avoid further dividing patients with low and high digital health literacy

Frailty and restrictions in geriatric domains are associated with surgical complications but not with radiation-induced acute toxicity in head and neck cancer patients:A prospective study

OBJECTIVES: We aimed to evaluate the association between frailty screening and geriatric assessment (GA) on short term adverse events in patients treated for head and neck cancer (HNC) for the first time in a prospective study. MATERIALS AND METHODS: Newly diagnosed HNC patients undergoing curative treatment were prospectively included in OncoLifeS, a data biobank. Prior to the start of treatment, frailty was assessed with a GA, Groningen Frailty Indicator (GFI) and Geriatric-8 (G8). The GA included comorbidity (Adult Comorbidity Evaluation - 27), nutritional status (Malnutrition Universal Screening Tool), functional status ((instrumental) Activities of Daily Living), mobility (Timed Up & Go), psychological (Geriatric Depression Scale 15) and cognitive (Mini Mental State Examination) measures. Clinically relevant postoperative complications (Clavien-Dindo ≥ grade 2) and acute radiation-induced toxicity (Common Terminology Criteria for Adverse Events version 4.0 ≥ grade 2) were defined as outcome measures. Univariable and multivariable logistic regression analyses were performed, yielding odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: Of the 369 included patients, 259 patients were eligible for analysis. Postoperative complications occurred in 41/148 (27.7%) patients and acute radiation-induced toxicity was present in 86/160 (53.7%) patients. Number of deficit domains of GA (OR = 1.71, 95%CI = 1.14-2.56), GFI (OR = 2.54, 95%CI = 1.02-6.31) and G8 (OR5.59, 95%CI = 2.14-14.60) were associated with postoperative complications, but not with radiation-induced toxicity. CONCLUSION: Frailty and restrictions in geriatric domains were associated with postoperative complications, but not with radiation-induced acute toxicity in curatively treated HNC patients. The results of this prospective study further emphasizes the importance of geriatric evaluation, particularly before surgery

Frailty is associated with decline in health-related quality of life of patients treated for head and neck cancer

Objective: To determine the effect of frailty on Health Related Quality of Life (HRQoL) after treatment for Head and Neck Cancer (HNC). Materials and methods: Patients were prospectively included in OncoLifeS, a data-biobank. Before treatment, patients underwent geriatric screening, including the Groningen Frailty Indicator (GFI) and Geriatric 8 (G8). Patients' HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) at three, six, twelve and twenty four months after treatment. Linear mixed models were used for statistical analysis. All models were adjusted for baseline HRQoL values, relevant confounders at baseline and yielded estimates (beta), 95% confidence intervals and p-values. Results: 288 patients were included. The mean age was 68.4 years and 68.8% were male. During follow-up, 84 patients had tumor recurrence and 66 died. Response to EORTC-QLQ-C30 ranged from 77.3% to 87.8%. Frail patients, defined by GFI, had significantly worse Global Health Status/Quality of Life (GHS/QoL) (beta = -8.70(-13.54;-3.86), p <0.001), physical functioning (beta = -4.55(-8.70;-0.40), p <0.032), emotional functioning (beta = -20.06(-25.65;-15.86), p <0.001), and social functioning (beta = -8.44(-13.91;-2.98), p <0.003) three months after treatment compared to non-frail patients. Furthermore, frail patients had a significantly worse course of GHS/QoL (j3 = -7.47(-11.23;-3.70), p = 0.001), physical functioning (beta = -3.28(-6.26;-0.31), p = 0.031) and role functioning (beta = -7.27(-12.26;-2.28), p = 0.005) over time, compared to non-frail patients. When frailty was determined by G8, frailty was significantly associated with worse GHS/QoL (beta = -6.68(-11.00;-2.37), p = 0.003) and emotional functioning (beta = -5.08(-9.43;-0.73), p = 0.022) three months after treatment. Conclusion: Frail patients are at increased risk for decline in HRQoL, and further deterioration during follow-up after treatment for HNC

Association of Deficits Identified by Geriatric Assessment With Deterioration of Health-Related Quality of Life in Patients Treated for Head and Neck Cancer

This cohort study assesses the association of single and accumulated geriatric deficits with health-related quality of life decline after treatment for head and neck cancer. Question Are pretreatment geriatric deficits associated with quality of life after treatment for head and neck cancer? Findings In this cohort study including 283 patients, items of geriatric assessment within all domains (physical, functional, psychological, social) were associated with decline of quality of life after treatment. The accumulation of domains with geriatric deficits was a major significant factor for deterioration at both short- and long-term follow-up after treatment. Meaning Deficits in individual and accumulated geriatric domains are associated with decline in quality of life; this knowledge may aid decision-making, indicate interventions, and reduce loss of quality of life. Importance Accumulation of geriatric deficits, leading to an increased frailty state, makes patients susceptible for decline in health-related quality of life (HRQOL) after treatment for head and neck cancer (HNC). Objective To assess the association of single and accumulated geriatric deficits with HRQOL decline in patients after treatment for HNC. Design, Setting, and Participants Between October 2014 and May 2016, patients at a tertiary referral center were included in the Oncological Life Study (OncoLifeS), a prospective data biobank, and followed up for 2 years. A consecutive series of 369 patients with HNC underwent geriatric assessment at baseline; a cohort of 283 patients remained eligible for analysis, and after 2 years, 189 patients remained in the study. Analysis was performed between March and November 2020. Interventions or Exposures Geriatric assessment included scoring of the Adult Comorbidity Evaluation 27, polypharmacy, Malnutrition Universal Screening Tool, Activities of Daily Living, Instrumental Activities of Daily Living (IADL), Timed Up & Go, Mini-Mental State Examination, 15-item Geriatric Depression Scale, marital status, and living situation. Main Outcomes and Measures The primary outcome measure was the Global Health Status/Quality of Life (GHS/QOL) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Differences between patients were evaluated using linear mixed models at 3 months after treatment (main effects, beta [95% CI]) and declining course per year during follow-up (interaction x time, beta [95% CI]), adjusted for baseline GHS/QOL scores, and age, sex, stage, and treatment modality. Results Among the 283 patients eligible for analysis, the mean (SD) age was 68.3 (10.9) years, and 193 (68.2%) were male. Severe comorbidity (beta = -7.00 [-12.43 to 1.56]), risk of malnutrition (beta = -6.18 [-11.55 to -0.81]), and IADL restrictions (beta = -10.48 [-16.39 to -4.57]) were associated with increased GHS/QOL decline at 3 months after treatment. Severe comorbidity (beta = -4.90 [-9.70 to -0.10]), IADL restrictions (beta = -5.36 [-10.50 to -0.22]), restricted mobility (beta = -6.78 [-12.81 to -0.75]), signs of depression (beta = -7.08 [-13.10 to -1.06]), and living with assistance or in a nursing home (beta = -8.74 [-15.75 to -1.73]) were associated with further GHS/QOL decline during follow-up. Accumulation of domains with geriatric deficits was a major significant factor for GHS/QOL decline at 3 months after treatment (per deficient domain beta = -3.17 [-5.04 to -1.30]) and deterioration during follow-up (per domain per year beta = -2.74 [-4.28 to -1.20]). Conclusions and Relevance In this prospective cohort study, geriatric deficits were significantly associated with HRQOL decline after treatment for HNC. Therefore, geriatric assessment may aid decision-making, indicate interventions, and reduce loss of HRQOL

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

A measurement of the millimetre emission and the Sunyaev-Zel'dovich effect associated with low-frequency radio sources

We present a statistical analysis of the millimetre-wavelength properties of 1.4GHz-selected sources and a detection of the Sunyaev–Zel’dovich (SZ) effect associated with the haloes that host them. We stack data at 148, 218 and 277GHz from the Atacama Cosmology Telescope at the positions of a large sample of radio AGN selected at 1.4GHz. The thermal SZ effect associated with the haloes that host the AGN is detected at the 5σ level through its spectral signature, representing a statistical detection of the SZ effect in some of the lowest mass haloes (average M 200 ≈ 10 13 M. h −1 70 ) studied to date. The relation between the SZ effect and mass (based on weak lensing measurements of radio galaxies) is consistent with that measured by Planck for local bright galaxies. In the context of galaxy evolution models, this study confirms that galaxies with radio AGN also typically support hot gaseous haloes. Adding Herschel observations allows us to show that the SZ signal is not significantly contaminated by dust emission. Finally, we analyse the contribution of radio sources to the angular power spectrum of the cosmic microwave background

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM)

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

Abstract: CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL