Brain-derived neurotrophic factor (BDNF) plays an essential role in neurogenesis and neuroplasticity and may be a key protein in cancer-related cognitive impairment (CRCI). This systematic review assessed the relationship between BDNF biomarkers and neurocognitive outcomes in cancer patients and survivors. A search in PubMed, Scopus, and PsycINFO yielded 638 articles, of which 26 were eligible. Fourteen (54 %) studied BDNF protein levels while 15 (58 %) analyzed BDNF rs6265 polymorphism. Of the nine observational studies reporting BDNF plasma/serum levels, five (56 %) exhibited a positive association between BDNF and cognitive function. One study reported intra-tumoral BDNF levels that were negatively associated with memory. For rs6265, three (20 %) of 15 studies reported an association with cognitive function with inconsistent directions. Among seven neuroimaging studies, three (43 %) demonstrated an effect of BDNF on brain function and structure. These results suggest that BDNF is a potential monitoring biomarker and druggable target for CRCI.

Background

About 4.5% of new cancer cases affect adolescent and young adult aged between 15 and 39 years in the United States (US). However, the effect of neuropsychiatric conditions on long-term adolescent and young adult cancer (AYAC) survivors has not been formally investigated. Thus, the impact and management of late neuropsychiatric complications in AYAC survivors compared to non-cancer-matched controls (NCMC) in the US were evaluated using the All of Us (AoU) Research Program.

Methods

Participants in the AoU Controlled Tier Dataset (v6) diagnosed with cancer between ages 15 and 39 were identified from electronic health records and surveys. AYAC survivors were matched with NCMC using the optimal pair-matching algorithm at a 1:4 ratio. Data on past diagnoses, current follow-up care, and treatment patterns of neuropsychiatric complications were collected.

Results

Analysis was performed on 788 AYAC survivors and 3152 NCMC. AYAC survivors, with an average of 8.8 years since their first cancer diagnosis, were more likely than NCMC to receive a diagnosis of neuropathy, memory loss and epilepsy (p  < 0.001). Survivors also had a higher rate of follow-up care and treatment utilization for these neurological conditions compared to NCMC (p  < 0.05). Treatment utilization was highest among survivors receiving care for epilepsy (88%), and lower for neuropathy (70%), memory loss (61%), and chronic fatigue (59%).

Conclusions

This large study reveals that AYAC survivors, on average 9 years after their cancer diagnosis, require more frequent follow-up care for neurological complications compared to non-cancer individuals. However, the management of neuropathy, memory loss, and chronic fatigue is hindered by a lack of mechanism-based effective therapies.

Background

We examined the research attitudes and willingness to participate in clinical research among cancer survivors with varying degrees of cognitive function.

Methods

This is a secondary analysis of data collected through the University of California Irvine Consent-to-Contact registry. Cancer survivors completed the Cognitive Function Instrument (CFI), the Research Attitudes Questionnaire (RAQ), and willingness to participate (WTP) in certain research procedures. Perceived cognitive impairment (CI) was defined as the worst 20% CFI scores.

Results

Here, 265 CI and 909 cognitively non-impaired (CNI) participants' data were analyzed. Mean age and sex distribution were similar, with fewer non-Hispanic Whites and education years among CI participants. More CI participants self-reported past diagnoses of Alzheimer's disease, mild cognitive impairment, stroke, depression, post-traumatic stress disorder, and alcohol abuse (all p < 0.05). CI participants were significantly more interested in studies investigating approved medications (92% vs. 87%, p = 0.030), lumbar puncture (47% vs. 38%, p = 0.027), and autopsy (78% vs. 69%, p = 0.022). After removing survivors with co-existing neuropsychiatric conditions, interest in autopsy studies remained statistically higher among CI (79% vs. 69%, p = 0.022).

Conclusions

Participants with cancer and CI are open to research procedures and interventions that are traditionally less utilized, which may facilitate the discovery of the pathogenesis and interventions for cancer-related cognitive impairment (CRCI).

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that is highly prevalent among cancer patients undergoing chemotherapy. There is a growing use of cryotherapy (CryTx) and compression therapy (ComTx) to prevent CIPN at cancer centers worldwide. In this study, we examined the awareness and recommendation of these modalities and evaluated factors associated with awareness. In addition, we investigated the type of technology utilized, barriers to implementation, and perceived adverse events of CryTx and ComTx.

Methods

Active members of the Multinational Association of Supportive Care of Cancer (MASCC) were invited to complete an electronic survey that was sent via SurveyMonkey between September and October 2021. The survey assessed participants' awareness, recommendation, usage, barriers to utilization, and perceived adverse events of CryTx and ComTx. Descriptive statistics and multiple logistic regression were utilized to analyze findings.

Results

Out of 184 participants, 70.1% were physicians, 73.4% had over 10 years of practice, and 49.5% were practicing in an outpatient setting. While more than half (63.3%) of participants indicated awareness of CryTx for taxane-induced peripheral neuropathy, less than a quarter (22.8%) indicated recommendation in their practice setting. Factors associated with higher awareness of CryTx for patients receiving taxanes include living in Europe (OR = 2.69, 95% CI [1.28-5.64], p = 0.009), not practicing in an inpatient setting (OR = 3.15, 95% CI [1.45-6.85], p = 0.004), and self-identifying as non-physician (OR = 2.40, 95% CI [1.03-4.37], p = 0.041). Commercial cooling (31.5%) and compression (16.8%) gloves and socks were the most used modalities for CryTx and ComTx, respectively. The most identified barriers to CryTx and ComTx utilization include insufficient evidence (53.5%), logistics (34.8%), and patient discomfort (23.4%). Redness/irritation of skin (27.7%) and numbness/tingling (24.5%) accounted for about half of the perceived adverse events associated with use of CryTx and ComTx.

Conclusion

Results of our global survey illustrated that there are varying modes in the delivery of CryTx and ComTx among cancer centers around the world. Education of the utilization of CryTx and ComTx, in addition to efficacy and implementation studies, is needed to close the gap between awareness and implementation in clinical practice.

Introduction

Identifying reliable biomarkers that reflect cancer survivorship symptoms remains a challenge for researchers. DNA methylation (DNAm) measurements reflecting epigenetic changes caused by anti-cancer therapy may provide needed insights. Given lack of consensus describing utilization of DNAm data to predict survivorship issues, a review evaluating the current landscape is warranted.

Objective

Provide an overview of current studies examining associations of DNAm with survivorship burdens in cancer survivors.

Methods

A literature review was conducted including studies if they focused on cohorts of cancer survivors, utilized peripheral blood cell DNAm data, and evaluated the associations of DNAm and survivorship issues.

Results

A total of 22 studies were identified, with majority focused on breast (n = 7) or childhood cancer (n = 9) survivors, and half studies included less than 100 patients (n = 11). Survivorship issues evaluated included those related to neurocognition (n = 5), psychiatric health (n = 3), general wellness (n = 9), chronic conditions (n = 5), and treatment specific toxicities (n = 4). Studies evaluated epigenetic age metrics (n = 10) and DNAm levels at individual CpG sites or regions (n = 12) for their associations with survivorship issues in cancer survivors along with relevant confounding factors. Significant associations of measured DNAm in the peripheral blood samples of cancer survivors and survivorship issues were identified.

Discussion/conclusion

Studies utilizing epigenetic age metrics and differential methylation analysis demonstrated significant associations of DNAm measurements with survivorship burdens. Associations were observed encompassing diverse survivorship outcomes and timeframes relative to anti-cancer therapy initiation. These findings underscore the potential of these measurements as useful biomarkers in survivorship care and research.

Background

This study evaluated the real-world impact of acupuncture on analgesics and healthcare resource utilization among breast cancer survivors.

Methods

From a United States (US) commercial claims database (25% random sample of IQVIA PharMetrics® Plus for Academics), we selected 18-63 years old malignant breast cancer survivors experiencing pain and ≥ 1 year removed from cancer diagnosis. Using the difference-in-difference technique, annualized changes in analgesics [prevalence, rates of short-term (< 30-day supply) and long-term (≥ 30-day supply) prescription fills] and healthcare resource utilization (healthcare costs, hospitalizations, and emergency department visits) were compared between acupuncture-treated and non-treated patients.

Results

Among 495 (3%) acupuncture-treated patients (median age: 55 years, stage 4: 12%, average 2.5 years post cancer diagnosis), most had commercial health insurance (92%) and experiencing musculoskeletal pain (98%). Twenty-seven percent were receiving antidepressants and 3% completed ≥ 2 long-term prescription fills of opioids. Prevalence of opioid usage reduced from 29 to 19% (P < 0.001) and NSAID usage reduced from 21 to 14% (P = 0.001) post-acupuncture. The relative prevalence of opioid and NSAID use decreased by 20% (P < 0.05) and 19% (P = 0.07), respectively, in the acupuncture-treated group compared to non-treated patients (n = 16,129). However, the reductions were not statistically significant after adjustment for confounding. Patients receiving acupuncture for pain (n = 264, 53%) were found with a relative decrease by 47% and 49% (both P < 0.05) in short-term opioid and NSAID fills compared to those treated for other conditions. High-utilization patients (≥ 10 acupuncture sessions, n = 178, 36%) were observed with a significant reduction in total healthcare costs (P < 0.001) unlike low-utilization patients.

Conclusions

Although adjusted results did not show that patients receiving acupuncture had better outcomes than non-treated patients, exploratory analyses revealed that patients treated specifically for pain used fewer analgesics and those with high acupuncture utilization incurred lower healthcare costs. Further studies are required to examine acupuncture effectiveness in real-world settings.

Introduction: Coronavirus 2019 (COVID-19) has had a devastating impact on mental health and access to addiction treatment in the United States, including in California, which resulted in the highest rates of emergency department visits (ED) for opioid poisoning in 2020. As California slowly returns to pre-pandemic normalcy, it remains uncertain whether the rates of opioid-related events have slowed down over time. We hypothesized that the number of opioid-related ED visits were exacerbated after the period of the COVID-19 pandemic and continue at a high rate in the present.

Methods: In this analysis we searched the University of California (UC) Health Data Warehouse—a database of electronic health records from six UC health centers—for opioid-related ED visits, identifiying using the following International Classification of Diseases, 10th Ed, Clinical Modification codes: F11 codes, and T40.0*, T40.1*, T40.2*, T40.3*, T40.4*, T40.6*. Opioid overdose-associated visits were classified by types of opioids involved: heroin (T40.1*); prescription opioids (T40.2* or T40.3*); and synthetic opioids (T40.4*). We performed interrupted time analysis to estimate the immediate (level) change and change-in-time trend (trend change), from before (January 2018–October 2019) and during the pandemic (April 2020–December 2022). Monthly visit rates were evaluated with negative binomial regression adjusted for first-order autoregression and using all-cause ED counts as the offset. We present effect sizes as rate ratios (RR) and 95% confidence intervals (CI), tested at α = .05.

Results: Before COVID-19, a steadily increasing trend in ED visit rates was observed for all outcomes (P < 0.05) except synthetic opioids. Total opioid-related ED visit rates increased by 15% (RR 1.15, 95%CI 1.02–1.29, P = 0.20) immediately after March 2020 before decreasing by 0.5% every month, albeit without statistical significance (RR .995, 95% CI .991–1.00, P = 0.06). Similar trends were observed with prescription opioid overdoses, with a step increase of 44% (RR 1.44, 95% CI 1.10–1.89, P = .008) before plateauing after March 2020 (RR 1.01, 95% CI .998–1.02, P = 0.12). After March 2020, ED visit rates for synthetic opioid overdoses were increasing steadily by 4% every month (RR 1.04, 95% CI 1.02–1.06, P = .001), unlike with heroin, which was observed with an 8% monthly reduction (RR .92, 95% CI .90–.93, P < .001). No immediate increase in visit rates was observed for either opioid.

Conclusion: While opioid-related ED admissions among the UC health centers showed an overall decrease, prescription and synthetic opioid overdoses remained significantly higher than pre-pandemic trends as of December 2022. A multilevel approach to improve awareness of new opioid health policies could ameliorate these alarming rises in the post-pandemic era.

Objective

Our previous studies have shown that "code blue" events can be predicted by SuperAlarm patterns that are multivariate combinations of monitor alarms and laboratory test results cooccurring frequently preceding the events but rarely among control patients. Deploying these patterns to the monitor data streams can generate SuperAlarm sequences. The objective of this study is to test the hypothesis that SuperAlarm sequences may contain more predictive sequential patterns than monitor alarms sequences.

Methods

Monitor alarms and laboratory test results are extracted from a total of 254 adult coded and 2213 control patients. The training dataset is composed of subsequences that are sampled from complete sequences and then further represented as fixed-dimensional vectors by the term frequency inverse document frequency method. The information gain technique and weighted support vector machine are adopted to select the most relevant features and train a classifier to differentiate sequences between coded patients and control patients. Performances are assessed based on an independent dataset using three metrics: sensitivity of lead time (Sen ^L @T), alarm frequency reduction rate (AFRR), and work-up to detection ratio (WDR).

Results

The performance of 12-h-long sequences of SuperAlarm can yield a Sen ^L@2 of 93.33%, an AFRR of 87.28%, and a WDR of 3.01. At an AFRR = 87.28%, Sen ^L@2 for raw alarm sequences and discretized alarm sequences are 73.33% and 70.19%, respectively. At a WDR = 3.01, Sen ^L@2 are 49.88% and 43.33%.

Conclusion and significance

The results demonstrate that SuperAlarm sequences indeed outperform monitor alarm sequences and suggest that one can focus on sequential patterns from SuperAlarm sequences to develop more precise patient monitoring solutions.

Purpose

Young adult childhood cancer survivors (YACCSs) are often impacted by cancer-related cognitive impairment (CRCI) and psychological distress. Using the Project Forward Cohort, we evaluated the relationship between CRCI and substance use behaviors.

Methods

YACCSs were surveyed between 2015 and 2018 (N = 1,106, female = 50.8%, Hispanic = 51.5%, median age = 25.5 years). Associations between CRCI and substance use (tobacco, binge drinking, marijuana, prescription drug misuse, and e-cigarette/vaporizer) were examined in multivariate logistic or log-binomial regressions, adjusting for child at diagnosis (0-14 years), years since diagnosis, sex, race/ethnicity, cancer type, and treatment intensity. Mediation analysis was performed to determine opportunities for interventions.

Results

CRCI was reported by 144 (13.0%) survivors. The highest prevalence was observed in CNS cancers (25.4%) and leukemia (13.3%) survivors. After covariate adjustment, CRCI was associated with 2.26 times the odds of prior 30-day vaping (95% CI, 1.24 to 4.11; P = .007). Mediators with significant indirect effects in the CRCI-vaping relationship include depressive symptoms (Center for Epidemiological Studies Depression Scale) and having two or more cancer-related late effects (P < .05).

Conclusion

CRCI among YACCSs was associated with reports of vaping. Oncologists should screen for vaping behavior if CRCI is apparent. Increasing access to long-term follow-up clinics, addressing physical and mental health issues, and monitoring and educating on vaping and other substance use behaviors is recommended to improve the long-term health of YACCSs.

We investigated 17 metrics derived from four leads of electrocardiographic (ECG) signals from hospital patient monitors to develop new ECG alarms for predicting adult bradyasystolic cardiac arrest events.A retrospective case-control study was designed to analyze 17 ECG metrics from 27 adult bradyasystolic and 304 control patients. The 17 metrics consisted of PR interval (PR), P-wave duration (Pdur), QRS duration (QRSdur), RR interval (RR), QT interval (QT), estimate of serum K  +  using only frontal leads (SerumK2), T-wave complexity (T Complex), ST segment levels for leads I, II, V (ST I, ST II, ST V), and 7 heart rate variability (HRV) metrics. These 7 HRV metrics were standard deviation of normal to normal intervals (SDNN), total power, very low frequency power, low frequency power, high frequency power, normalized low frequency power, and normalized high frequency power. Controls were matched by gender, age (±5 years), admission to the same hospital unit within the same month, and the same major diagnostic category. A research ECG analysis software program developed by co-author D M was used to automatically extract the metrics. The absolute value for each ECG metric, and the duration, terminal value, and slope of the dominant trend for each ECG metric, were derived and tested as the alarm conditions. The maximal true positive rate (TPR) of detecting cardiac arrest at a prescribed maximal false positive rate (FPR) based on the trending conditions was reported. Lead time was also recorded as the time between the first time alarm condition was triggered and the event of cardiac arrest.While conditions based on the absolute values of ECG metrics do not provide discriminative information to predict bradyasystolic cardiac arrest, the trending conditions can be useful. For example, with a max FPR  =  5.0%, some derived alarms conditions are: trend duration of PR  >  2.8 h (TPR  =  48.2%, lead time  =  10.0  ±  6.6 h), trend duration of QRSdur  >  2.7 h (TPR  =  40.7%, lead time  =  8.8  ±  6.2 h), trend duration of RR  >  3.5 h (TPR  =  51.9%, lead time  =  6.4  ±  5.5 h), trend duration of T Complex  >  2.9 h (TPR  =  40.7%, lead time  =  6.8  ±  5.5 h), trend duration of ST I  >  3.0 h (TPR of 51.9%, lead time  =  8.4  ±  8.0 h), trend duration of SDNN  >  3.6 h (TPR of 40.7%, lead time  =  11.0  ±  8.6 h), trend duration of HRV total power  >  3.0 h (TPR of 25.9%, lead time  =  7.5  ±  8.1 h), terminal value of ST I  <  -56 µV (TPR  =  22.2%, lead time  =  12.8  ±  8.3 h), and slope of QR  >  19.4 ms h(-1) (TPR  =  25.9%, lead time  =  6.7  ±  6.9 h). Eleven trend duration alarms, eight terminal value alarms, and ten slope alarms, achieved a positive TPR with zero FPR. Furthermore, these alarms conditions with zero PFR can be combined by the 'OR'logic could further improve the TPR without increasing the FPR.The trend duration, terminal value, and slope of the dominant trend of the ECG metrics considered in this study are able to predict a subset of patients with bradyasystolic cardiac arrests with low or even zero FPR, which can be used for developing new ECG alarms.