Prospective validation of smartphone-based heart rate and respiratory rate measurement algorithms.

Background: Measuring vital signs plays a key role in both patient care and wellness, but can be challenging outside of medical settings due to the lack of specialized equipment. Methods: In this study, we prospectively evaluated smartphone camera-based techniques for measuring heart rate (HR) and respiratory rate (RR) for consumer wellness use. HR was measured by placing the finger over the rear-facing camera, while RR was measured via a video of the participants sitting still in front of the front-facing camera. Results: In the HR study of 95 participants (with a protocol that included both measurements at rest and post exercise), the mean absolute percent error (MAPE) ± standard deviation of the measurement was 1.6% ± 4.3%, which was significantly lower than the pre-specified goal of 5%. No significant differences in the MAPE were present across colorimeter-measured skin-tone subgroups: 1.8% ± 4.5% for very light to intermediate, 1.3% ± 3.3% for tan and brown, and 1.8% ± 4.9% for dark. In the RR study of 50 participants, the mean absolute error (MAE) was 0.78 ± 0.61 breaths/min, which was significantly lower than the pre-specified goal of 3 breaths/min. The MAE was low in both healthy participants (0.70 ± 0.67 breaths/min), and participants with chronic respiratory conditions (0.80 ± 0.60 breaths/min). Conclusions: These results validate the accuracy of our smartphone camera-based techniques to measure HR and RR across a range of pre-defined subgroups.

Impact of mental illness on end-of-life emergency department use in elderly patients with gastrointestinal malignancies.

BACKGROUND: Elderly patients with gastrointestinal cancer and mental illness have significant comorbidities that can impact the quality of their care. We investigated the relationship between mental illness and frequent emergency department (ED) use in the last month of life, an indicator for poor end-of-life care quality, among elderly patients with gastrointestinal cancers. METHODS: We used SEER-Medicare data to identify decedents with gastrointestinal cancers who were diagnosed between 2004 and 2013 and were at least 66 years old at time of diagnosis (median age: 80 years, range: 66-117 years). We evaluated the association between having a diagnosis of depression, bipolar disorders, psychotic disorders, anxiety, dementia, and/or substance use disorders and ED use in the last 30 days of life using logistic regression models. RESULTS: Of 160,367 patients included, 54,661 (34.1%) had a mental illness diagnosis between one year prior to cancer diagnosis and death. Patients with mental illness were more likely to have > 1 ED visit in the last 30 days of life (15.6% vs. 13.3%, p < 0.01). ED use was highest among patients with substance use (17.7%), bipolar (16.5%), and anxiety disorders (16.4%). Patients with mental illness who were male, younger, non-white, residing in lower income areas, and with higher comorbidity were more likely to have multiple end-of-life ED visits. Patients who received outpatient treatment from a mental health professional were less likely to have multiple end-of-life ED visits (adjusted odds ratio 0.82, 95% confidence interval 0.78-0.87). CONCLUSIONS: In elderly patients with gastrointestinal cancers, mental illness is associated with having multiple end-of-life ED visits. Increasing access to mental health services may improve quality of end-of-life care in this vulnerable population.

Longitudinal Analysis of Mental Disorder Burden Among Elderly Patients With Gastrointestinal Malignancies.

BACKGROUND: Patients with cancer are at high risk for having mental disorders, resulting in widespread psychosocial screening efforts. However, there is a need for population-based and longitudinal studies of mental disorders among patients who have gastrointestinal cancer and particular among elderly patients. PATIENTS AND METHODS: We used the SEER-Medicare database to identify patients aged ≥65 years with colorectal, pancreatic, gastric, hepatic/biliary, esophageal, or anal cancer. Earlier (12 months before or up to 6 months after cancer diagnosis) and subsequent mental disorder diagnoses were identified. RESULTS: Of 112,283 patients, prevalence of an earlier mental disorder was 21%, 23%, 20%, 20%, 19%, and 26% for colorectal, pancreatic, gastric, hepatic/biliary, esophageal, and anal cancer, respectively. An increased odds of an earlier mental disorder was associated with pancreatic cancer (odds ratio [OR], 1.17; 95% CI, 1.11-1.23), esophageal cancer (OR, 1.10; 95% CI, 1.02-1.18), and anal cancer (OR, 1.17; 95% CI, 1.05-1.30) compared with colorectal cancer and with having regional versus local disease (OR, 1.09; 95% CI, 1.06-1.13). The cumulative incidence of a subsequent mental disorder at 5 years was 19%, 16%, 14%, 13%, 12%, and 10% for patients with anal, colorectal, esophageal, gastric, hepatic/biliary, and pancreatic cancer, respectively. There was an association with having regional disease (hazard ratio [HR], 1.08; 95% CI, 1.04-1.12) or distant disease (HR, 1.36; 95% CI, 1.28-1.45) compared with local disease and the development of a mental disorder. Although the development of a subsequent mental disorder was more common among patients with advanced cancers, there continued to be a significant number of patients with earlier-stage disease at risk. CONCLUSIONS: This study suggests a larger role for incorporating psychiatric symptom screening and management throughout oncologic care.

The clinical and financial cost of mental disorders among elderly patients with gastrointestinal malignancies.

The clinical and financial effects of mental disorders are largely unknown among gastrointestinal (GI) cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified patients whose first cancer was a primary colorectal, pancreatic, gastric, hepatic/biliary, esophageal, or anal cancer as well as those with coexisting depression, anxiety, psychotic, or bipolar disorder. Survival, chemotherapy use, total healthcare expenditures, and patient out-of-pocket expenditures were estimated and compared based on the presence of a mental disorder. We identified 112,283 patients, 23,726 (21%) of whom had a coexisting mental disorder. Median survival for patients without a mental disorder was 52 months (95% CI 50-53 months) and for patients with a mental disorder was 43 months (95% CI 42-44 months) (p < 0.001). Subgroup analysis identified patients with colorectal, gastric, or anal cancer to have a significant association between survival and presence of a mental disorder. Chemotherapy use was lower among patients with a mental disorder within regional colorectal cancer (43% vs. 41%, p = 0.01) or distant colorectal cancer subgroups (71% vs. 63%, p < 0.0001). The mean total healthcare expenditures were higher for patients with a mental disorder in first year following the cancer diagnosis (increase of $16,823, 95% CI $15,777-$18,173), and mean patient out-of-pocket expenses were also higher (increase of $1,926, 95% CI $1753-$2091). There are a substantial number of GI cancer patients who have a coexisting mental disorder, which is associated with inferior survival, higher healthcare expenditures, and greater personal financial burden.

Intensified systemic therapy and stereotactic ablative radiotherapy dose for patients with unresectable pancreatic adenocarcinoma.

PURPOSE: We aimed to report the long-term impact of modern chemotherapy and SABR dose regimens on oncologic outcomes of unresectable pancreatic adenocarcinoma (PA). MATERIALS AND METHODS: We reviewed the treatment characteristics and outcomes of all patients who received multi-fraction SABR for unresectable PA between February 2007 and August 2018 at our institution. Time-to-events were calculated from date of diagnosis treating death as a competing risk. RESULTS: A total of 149 patients were identified. Median follow-up was 15 months (range: 5-47). Median SABR dose was 33 Gy (range: 20-45) delivered in 5 fractions in 143 patients, and 3 or 6 fractions in 6 patients. 107 patients (72%) received gemcitabine-based chemotherapy while 31 (21%) received modified FOLFIRINOX (mFFX). Median OS was 16 months (95% CI, 14-17), with a 1-year cumulative incidence of LF of 14%. The combination of SABR doses ≥40 Gy and mFFX (n = 21) showed a superior PFS and OS to the use of GEM-based chemotherapy with <40 Gy SABR doses (median PFS: 14 vs. 10 months, HR: 0.46, 95% CI: 0.29-0.71, P = 0.003; median OS: 24 vs. 14 months, HR: 0.36, 95% CI: 0.22-0.59, P = 0.002), with 1-year PFS and OS of 67% and 90% compared to 35% and 59% for those who received GEM-based chemotherapy with <40 Gy SABR doses, respectively. CONCLUSIONS: The use of mFFX and a SABR dose ≥40 Gy in 5 fractions may be superior compared to regimens that utilize gemcitabine-based chemotherapy or SABR doses <40 Gy.

Development and validation of phenotype classifiers across multiple sites in the observational health data sciences and informatics network.

OBJECTIVE: Accurate electronic phenotyping is essential to support collaborative observational research. Supervised machine learning methods can be used to train phenotype classifiers in a high-throughput manner using imperfectly labeled data. We developed 10 phenotype classifiers using this approach and evaluated performance across multiple sites within the Observational Health Data Sciences and Informatics (OHDSI) network. MATERIALS AND METHODS: We constructed classifiers using the Automated PHenotype Routine for Observational Definition, Identification, Training and Evaluation (APHRODITE) R-package, an open-source framework for learning phenotype classifiers using datasets in the Observational Medical Outcomes Partnership Common Data Model. We labeled training data based on the presence of multiple mentions of disease-specific codes. Performance was evaluated on cohorts derived using rule-based definitions and real-world disease prevalence. Classifiers were developed and evaluated across 3 medical centers, including 1 international site. RESULTS: Compared to the multiple mentions labeling heuristic, classifiers showed a mean recall boost of 0.43 with a mean precision loss of 0.17. Performance decreased slightly when classifiers were shared across medical centers, with mean recall and precision decreasing by 0.08 and 0.01, respectively, at a site within the USA, and by 0.18 and 0.10, respectively, at an international site. DISCUSSION AND CONCLUSION: We demonstrate a high-throughput pipeline for constructing and sharing phenotype classifiers across sites within the OHDSI network using APHRODITE. Classifiers exhibit good portability between sites within the USA, however limited portability internationally, indicating that classifier generalizability may have geographic limitations, and, consequently, sharing the classifier-building recipe, rather than the pretrained classifiers, may be more useful for facilitating collaborative observational research.

Predicting per-lesion local recurrence in locally advanced non-small cell lung cancer following definitive radiation therapy using pre- and mid-treatment metabolic tumor volume.

BACKGROUND: We evaluated whether pre- and mid-treatment metabolic tumor volume (MTV) predicts per lesion local recurrence (LR) in patients treated with definitive radiation therapy (RT, dose≥60 Gy) for locally advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed records of patients with stage III NSCLC treated from 2006 to 2018 with pre- and mid-RT PET-CT. We measured the MTV of treated lesions on the pre-RT (MTVpre) and mid-RT (MTVmid) PET-CT. LR was defined per lesion as recurrence within the planning target volume. Receiver operating characteristic (ROC) curves, cumulative incidence rates, and uni- and multivariable (MVA) competing risk regressions were used to evaluate the association between MTV and LR. RESULTS: We identified 111 patients with 387 lesions (112 lung tumors and 275 lymph nodes). Median age was 68 years, 69.4% were male, 46.8% had adenocarcinoma, 39.6% had squamous cell carcinoma, and 95.5% received concurrent chemotherapy. Median follow-up was 38.7 months. 3-year overall survival was 42.3%. 3-year cumulative incidence of LR was 26.8% per patient and 11.9% per lesion. Both MTVpre and MTVmid were predictive of LR by ROC (AUC = 0.71 and 0.76, respectively) and were significantly associated with LR on MVA (P = 0.004 and P = 7.1e-5, respectively). Among lesions at lower risk of LR based on MTVpre, higher MTVmid was associated with LR (P = 0.001). CONCLUSION: Per-lesion, larger MTVpre and MTVmid predicted for increased risk of LR. MTVmid was more highly predictive of LR than MTVpre and if validated may allow for further discrimination of high-risk lesions at mid-RT informing dose painting strategies.

SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age.

L1 retrotransposons are an abundant class of transposable elements that pose a threat to genome stability and may have a role in age-related pathologies such as cancer. Recent evidence indicates that L1s become more active in somatic tissues during the course of ageing; however the mechanisms underlying this phenomenon remain unknown. Here we report that the longevity regulating protein, SIRT6, is a powerful repressor of L1 activity. Specifically, SIRT6 binds to the 5'-UTR of L1 loci, where it mono-ADP ribosylates the nuclear corepressor protein, KAP1, and facilitates KAP1 interaction with the heterochromatin factor, HP1α, thereby contributing to the packaging of L1 elements into transcriptionally repressive heterochromatin. During the course of ageing, and also in response to DNA damage, however, we find that SIRT6 is depleted from L1 loci, allowing the activation of these previously silenced retroelements.