Missing data imputation techniques for wireless continuous vital signs monitoring

Wireless vital signs sensors are increasingly used for remote patient monitoring, but data analysis is often challenged by missing data periods. This study explored the performance of various imputation techniques for continuous vital signs measurements. Wireless vital signs measurements (heart rate, respiratory rate, blood oxygen saturation, axillary temperature) from surgical ward patients were used for repeated random simulation of missing data periods (gaps) of 5–60 min in two-hour windows. Gaps were imputed using linear interpolation, spline interpolation, last observation- and mean carried forwards technique, and cluster-based prognosis. Imputation performance was evaluated using the mean absolute error (MAE) between original and imputed gap samples. Besides, effects on signal features (window’s slope, mean) and early warning scores (EWS) were explored. Gaps were simulated in 1743 data windows, obtained from 52 patients. Although MAE ranges overlapped, median MAE was structurally lowest for linear interpolation (heart rate: 0.9–2.6 beats/min, respiratory rate: 0.8–1.8 breaths/min, temperature: 0.04–0.17 °C, oxygen saturation: 0.3–0.7% for 5–60 min gaps) but up to twice as high for other techniques. Three techniques resulted in larger ranges of signal feature bias compared to no imputation. Imputation led to EWS misclassification in 1–8% of all simulations. Imputation error ranges vary between imputation techniques and increase with gap length. Imputation may result in larger signal feature bias compared to performing no imputation, and can affect patient risk assessment as illustrated by the EWS. Accordingly, careful implementation and selection of imputation techniques is warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10877-023-00975-w

MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation

Hypermethylation of the MGMT gene promoter and mutation of the TP53 tumor-suppressor gene are frequently present in diffuse astrocytomas. However, there is only anecdotal information about MGMT methylation status and TP53 mutations during progression of low-grade diffuse astrocytoma (AII) to anaplastic astrocytoma (AIII) and secondary glioblastoma (sGB). In this study biopsy specimens from 51 patients with astrocytic tumors with radiologically proved progression from low to high-grade malignancy were investigated for the presence and consistency of MGMT promoter hypermethylation and TP53 mutations. For 27 patients biopsy samples both of primary tumors and their recurrences were available. For the other 24 patients histology of either the low-grade lesion or the high-grade recurrence was available. It was found that MGMT promoter hypermethylation and TP53 mutations are both frequent and early events in the progression of astrocytomas and that their status is consistent over time. No correlation was found between MGMT methylation status and the presence of TP53 mutations. In addition, no correlation was found between MGMT promoter hypermethylation and the type of TP53 mutations. These results argue against the putative TP53 G:C>A:T transition mutations suggested to occur preferentially in MGMT hypermethylated tumors

Early Warning Scores to Support Continuous Wireless Vital Sign Monitoring for Complication Prediction in Patients on Surgical Wards:Retrospective Observational Study

Background: Wireless vital sign sensors are increasingly being used to monitor patients on surgical wards. Although early warning scores (EWSs) are the current standard for the identification of patient deterioration in a ward setting, their usefulness for continuous monitoring is unknown.Objective: This study aimed to explore the usability and predictive value of high-rate EWSs obtained from continuous vital sign recordings for early identification of postoperative complications and compares the performance of a sensor-based EWS alarm system with manual intermittent EWS measurements and threshold alarms applied to individual vital sign recordings (single-parameter alarms).Methods: Continuous vital sign measurements (heart rate, respiratory rate, blood oxygen saturation, and axillary temperature) collected with wireless sensors in patients on surgical wards were used for retrospective simulation of EWSs (sensor EWSs) for different time windows (1-240 min), adopting criteria similar to EWSs based on manual vital signs measurements (nurse EWSs). Hourly sensor EWS measurements were compared between patients with (event group: 14/46, 30%) and without (control group: 32/46, 70%) postoperative complications. In addition, alarms were simulated for the sensor EWSs using a range of alarm thresholds (1-9) and compared with alarms based on nurse EWSs and single-parameter alarms. Alarm performance was evaluated using the sensitivity to predict complications within 24 hours, daily alarm rate, and false discovery rate (FDR). Results: The hourly sensor EWSs of the event group (median 3.4, IQR 3.1-4.1) was significantly higher (P&lt;.004) compared with the control group (median 2.8, IQR 2.4-3.2). The alarm sensitivity of the hourly sensor EWSs was the highest (80%-67%) for thresholds of 3 to 5, which was associated with alarm rates of 2 (FDR=85%) to 1.2 (FDR=83%) alarms per patient per day respectively. The sensitivity of sensor EWS–based alarms was higher than that of nurse EWS–based alarms (maximum=40%) but lower than that of single-parameter alarms (87%) for all thresholds. In contrast, the (false) alarm rates of sensor EWS–based alarms were higher than that of nurse EWS–based alarms (maximum=0.6 alarm/patient/d; FDR=80%) but lower than that of single-parameter alarms (2 alarms/patient/d; FDR=84%) for most thresholds. Alarm rates for sensor EWSs increased for shorter time windows, reaching 70 alarms per patient per day when calculated every minute.Conclusions: EWSs obtained using wireless vital sign sensors may contribute to the early recognition of postoperative complications in a ward setting, with higher alarm sensitivity compared with manual EWS measurements. Although hourly sensor EWSs provide fewer alarms compared with single-parameter alarms, high false alarm rates can be expected when calculated over shorter time spans. Further studies are recommended to optimize care escalation criteria for continuous monitoring of vital signs in a ward setting and to evaluate the effects on patient outcomes.</p

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention in adolescent and young adult (AYA) cancer survivors:results from the SURVAYA study

Purpose: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. Methods: A population-based, cross-sectional study was performed among long-term (5–20 years) AYA cancer survivors (18–39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. Results: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5–7.0) (n = 3668). Sixty-one percent adhered to “limit the consumption of sugar sweetened drinks,” 28% to “be a healthy weight,” 25% to “fruit and vegetable consumption,” and 31% to “limit alcohol consumption.” Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14–1.85, and ORhigh = 1.87, 95% CI = 1.46–2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30–1.83, and ORhigh = 1.87, 95% CI = 1.46–2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50–0.92, and ORhigh = 0.30, 95% CI = 0.21–0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39–0.86, and ORhigh = 0.45, 95% CI = 0.30–0.69). Conclusions: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. Implications for Cancer Survivors: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.</p

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention in adolescent and young adult (AYA) cancer survivors:results from the SURVAYA study

Purpose: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. Methods: A population-based, cross-sectional study was performed among long-term (5–20 years) AYA cancer survivors (18–39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. Results: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5–7.0) (n = 3668). Sixty-one percent adhered to “limit the consumption of sugar sweetened drinks,” 28% to “be a healthy weight,” 25% to “fruit and vegetable consumption,” and 31% to “limit alcohol consumption.” Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14–1.85, and ORhigh = 1.87, 95% CI = 1.46–2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30–1.83, and ORhigh = 1.87, 95% CI = 1.46–2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50–0.92, and ORhigh = 0.30, 95% CI = 0.21–0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39–0.86, and ORhigh = 0.45, 95% CI = 0.30–0.69). Conclusions: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. Implications for Cancer Survivors: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.</p

Patient-Reported Outcomes of Accelerated Aging:A Novel Approach to Investigate Second Cancer Risk in Adolescent and Young Adult (18-39 Years) Cancer Survivors

Background: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. Patients and Methods: Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. Results:In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. Conclusion: AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer.</p

Pre-treatment fertility preservation and post-treatment reproduction in long-term survivors of adolescent and young adult (AYA) cancer

Purpose: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18–39 years) cancer. Methods: This study included n = 1457 male and n = 2112 female long-term survivors (M age = 43–45 years; 5–22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry.Results: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2–3.6]), not having children (OR = 5.0; 95%CI [3.2–7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to “others”), and more intense treatments (OR = 1.5; 95%CI [1.1–2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. Conclusions: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors’ well-being. Implications for Cancer Survivors: The extent to which cryopreservation positively affects survivors’ well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.</p

Pre-treatment fertility preservation and post-treatment reproduction in long-term survivors of adolescent and young adult (AYA) cancer

Purpose: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18–39 years) cancer. Methods: This study included n = 1457 male and n = 2112 female long-term survivors (M age = 43–45 years; 5–22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry.Results: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2–3.6]), not having children (OR = 5.0; 95%CI [3.2–7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to “others”), and more intense treatments (OR = 1.5; 95%CI [1.1–2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. Conclusions: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors’ well-being. Implications for Cancer Survivors: The extent to which cryopreservation positively affects survivors’ well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.</p

Exploring the interconnectedness between health-related quality of life factors among long-term adolescent and young adult cancer survivors (AYAs):a network analysis

Purpose: Adolescent and young adult cancer survivors (AYAs) are at increased risk of long-term and late effects, and experience unmet needs, impacting their health-related quality of life (HRQoL). In order to provide and optimize supportive care and targeted interventions for this unique population, it is important to study HRQoL factors’ interconnectedness on a population level. Therefore, this network analysis was performed with the aim to explore the interconnectedness between HRQoL factors, in the analysis described as nodes, among long-term AYAs. Methods: This population-based cohort study used cross-sectional survey data of long-term AYAs, who were identified by the Netherlands Cancer Registry (NCR). Participants completed a one-time survey (SURVAYA study), including the EORTC survivorship questionnaire (QLQ-SURV111) to assess their long-term HRQoL outcomes and sociodemographic characteristics. The NCR provided the clinical data. Descriptive statistics and a network analysis, including network clustering, were performed. Results: In total, 3596 AYAs (on average 12.4 years post diagnosis) were included in our network analysis. The network was proven stable and reliable and, in total, four clusters were identified, including a worriment, daily functioning, psychological, and sexual cluster. Negative health outlook, part of the worriment cluster, was the node with the highest strength and its partial correlation with health distress was significantly different from all other partial correlations. Conclusion: This study shows the results of a stable and reliable network analysis based on HRQoL data of long-term AYAs, and identified nodes, correlations, and clusters that could be intervened on to improve the HRQoL outcomes of AYAs.</p