Association of Remote Patient-Reported Outcomes and Step Counts With Hospitalization or Death Among Patients With Advanced Cancer Undergoing Chemotherapy: Secondary Analysis of the PROStep Randomized Trial.

BACKGROUND: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. OBJECTIVE: The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. METHODS: The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. RESULTS: Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively. CONCLUSIONS: In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054675.

Remote Patient-Reported Outcomes and Activity Monitoring to Improve Patient-Clinician Communication Regarding Symptoms and Functional Status: A Randomized Controlled Trial.

PURPOSE: Routine collection of patient-generated health data (PGHD) may promote earlier recognition of symptomatic and functional decline. This trial assessed the impact of an intervention integrating remote PGHD collection with patient nudges on symptom and functional status understanding between patients with advanced cancer and their oncology team. METHODS: This three-arm randomized controlled trial was conducted from November 19, 2020, to December 17, 2021, at a large tertiary oncology practice. We enrolled patients with stage IV GI and lung cancers undergoing chemotherapy. Over 6 months, patients in two intervention arms received PROStep-weekly text message-based symptom surveys and passive activity monitoring using a wearable accelerometer. PGHD were summarized in dashboards given to patients' oncology team before appointments. One intervention arm received an additional text-based active choice prompt to discuss worsening symptoms or functional status with their clinician. Control patients did not receive PROStep. The coprimary outcomes patient perceptions of oncology team symptom and functional understanding at 6 months were measured on a 1-5 Likert scale (5 = high understanding). RESULTS: One hundred eight patients enrolled: 55% male, 81% White, and 77% had GI cancers. Patient-reported clinician understanding did not differ between control and intervention arms for symptoms (4.5 v 4.5; P = .87) or functional status (4.5 v 4.3; P = .31). In the intervention arms, combined patient adherence to weekly symptom reports and daily activity monitoring was 64% and 53%, respectively. Intervention patients in the PROStep versus PROStep + active choice arms reported low burden from wearing the accelerometer (mean burden [standard deviation], 2.7 [1.3] v 2.1 [1.3]; P = .15) and completing surveys (2.1 [1.2] v 1.9 [1.3]; P = .44). CONCLUSION: Patients receiving PROStep reported high understanding of symptoms and functional status from their oncology team, although this did not differ from controls.

A Natural Language Processing-Assisted Extraction System for Gleason Scores: Development and Usability Study.

BACKGROUND: Natural language processing (NLP) offers significantly faster variable extraction compared to traditional human extraction but cannot interpret complicated notes as well as humans can. Thus, we hypothesized that an "NLP-assisted" extraction system, which uses humans for complicated notes and NLP for uncomplicated notes, could produce faster extraction without compromising accuracy. OBJECTIVE: The aim of this study was to develop and pilot an NLP-assisted extraction system to leverage the strengths of both human and NLP extraction of prostate cancer Gleason scores. METHODS: We collected all available clinical and pathology notes for prostate cancer patients in an unselected academic biobank cohort. We developed an NLP system to extract prostate cancer Gleason scores from both clinical and pathology notes. Next, we designed and implemented the NLP-assisted extraction system algorithm to categorize notes into "uncomplicated" and "complicated" notes. Uncomplicated notes were assigned to NLP extraction and complicated notes were assigned to human extraction. We randomly reviewed 200 patients to assess the accuracy and speed of our NLP-assisted extraction system and compared it to NLP extraction alone and human extraction alone. RESULTS: Of the 2051 patients in our cohort, the NLP system extracted a prostate surgery Gleason score from 1147 (55.92%) patients and a prostate biopsy Gleason score from 1624 (79.18%) patients. Our NLP-assisted extraction system had an overall accuracy rate of 98.7%, which was similar to the accuracy of human extraction alone (97.5%; P=.17) and significantly higher than the accuracy of NLP extraction alone (95.3%; P<.001). Moreover, our NLP-assisted extraction system reduced the workload of human extractors by approximately 95%, resulting in an average extraction time of 12.7 seconds per patient (vs 256.1 seconds per patient for human extraction alone). CONCLUSIONS: We demonstrated that an NLP-assisted extraction system was able to achieve much faster Gleason score extraction compared to traditional human extraction without sacrificing accuracy.

Risk of Persistent Opioid Use following Major Surgery in Matched Samples of Patients with and without Cancer.

BACKGROUND: The opioid crisis has reached epidemic proportions, yet risk of persistent opioid use following curative intent surgery for cancer and factors influencing this risk are not well understood. METHODS: We used electronic health record data from 3,901 adult patients who received a prescription for an opioid analgesic related to hysterectomy or large bowel surgery from January 1, 2013, through June 30, 2018. Patients with and without a cancer diagnosis were matched on the basis of demographic, clinical, and procedural variables and compared for persistent opioid use. RESULTS: Cancer diagnosis was associated with greater risk for persistent opioid use after hysterectomy [18.9% vs. 9.6%; adjusted OR (aOR), 2.26; 95% confidence interval (CI), 1.38-3.69; P = 0.001], but not after large bowel surgery (28.3% vs. 24.1%; aOR 1.25; 95% CI, 0.97-1.59; P = 0.09). In the cancer hysterectomy cohort, persistent opioid use was associated with cancer stage (increased rates among those with stage III cancer compared with stage I) and use of neoadjuvant or adjuvant chemotherapy; however, these factors were not associated with persistent opioid use in the large bowel cohort. CONCLUSIONS: Patients with cancer may have an increased risk of persistent opioid use following hysterectomy. IMPACT: Risks and benefits of opioid analgesia for surgical pain among patients with cancer undergoing hysterectomy should be carefully considered.

Implementation of a Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: the Optimizing Antibiotic Strategies in Sepsis (OASIS) II Study.

BACKGROUND: Biomarkers can facilitate safe antibiotic discontinuation in critically ill patients without bacterial infection. METHODS: We tested the ability of a biomarker-based algorithm to reduce excess antibiotic administration in patients with systemic inflammatory response syndrome (SIRS) without bacterial infections (uninfected) in our pediatric intensive care unit (PICU). The algorithm suggested that PICU clinicians stop antibiotics if (1) C-reactive protein <4 mg/dL and procalcitonin <1 ng/mL at SIRS onset and (2) no evidence of bacterial infection by exam/testing by 48 hours. We evaluated excess broad-spectrum antibiotic use, defined as administration on days 3-9 after SIRS onset in uninfected children. Incidence rate ratios (IRRs) compared unadjusted excess length of therapy (LOT) in the 34 months before (Period 1) and 12 months after (Period 2) implementation of this algorithm, stratified by biomarker values. Segmented linear regression evaluated excess LOT among all uninfected episodes over time and between the periods. RESULTS: We identified 457 eligible SIRS episodes without bacterial infection, 333 in Period 1 and 124 in Period 2. When both biomarkers were below the algorithm's cut-points (n = 48 Period 1, n = 31 Period 2), unadjusted excess LOT was lower in Period 2 (IRR, 0.53; 95% confidence interval, 0.30-0.93). Among all 457 uninfected episodes, there were no significant differences in LOT (coefficient 0.9, P = .99) between the periods on segmented regression. CONCLUSIONS: Implementation of a biomarker-based algorithm did not decrease overall antibiotic exposure among all uninfected patients in our PICU, although exposures were reduced in the subset of SIRS episodes where biomarkers were low.

Clinical Features and Outcomes of Children with Culture-Negative Septic Arthritis.

BACKGROUND: Septic arthritis is a serious infection, but the results of blood and joint fluid cultures are often negative in children. We describe here the clinical features and management of culture-negative septic arthritis in children at our hospital and their outcomes. METHODS: We performed a retrospective review of a cohort of children with septic arthritis who were hospitalized at Children's Hospital of Philadelphia between January 2002 and December 2014. Culture-negative septic arthritis was defined as a joint white blood cell count of >50000/µL with associated symptoms, a clinical diagnosis of septic arthritis, and a negative culture result. Children with pretreatment, an intensive case unit admission, Lyme arthritis, immunodeficiency, or surgical hardware were excluded. Treatment failure included a change in antibiotics, surgery, and/or reevaluation because of a lack of improvement/worsening. RESULTS: We identified 157 children with septic arthritis. The patients with concurrent osteomyelitis (n = 28) had higher inflammatory marker levels at presentation, had a longer duration of symptoms (median, 4.5 vs 3 days, respectively; P < .001), and more often had bacteremia (46.4% vs 6.2%, respectively; P < .001). Among children with septic arthritis without associated osteomyelitis, 69% (89 of 129) had negative culture results. These children had lower C-reactive protein levels (median, 4.0 vs 7.3 mg/dL, respectively; P = .001) and erythrocyte sedimentation rates (median, 39 vs 51 mm/hour, respectively; P = .01) at admission and less often had foot/ankle involvement (P = .02). Among the children with culture-negative septic arthritis, the inpatient treatment failure rate was 9.1%, and treatment failure was more common in boys than in girls (17.1% vs 3.8%, respectively; P = .03). We found no association between treatment failure and empiric antibiotics or patient age. No outpatient treatment failures occurred during the 6-month follow-up period, although 17% of the children discharged with a peripherally inserted central catheter line experienced complications, including 3 with bacteremia. CONCLUSIONS: The majority of septic arthritis infections at our institution were culture negative. Among patients with culture-negative infection, empiric antibiotics failed for 9% and necessitated a change in therapy. More sensitive diagnostic testing should be implemented to elucidate the causes of culture-negative septic arthritis in children.

Relationship of SULT1A1 copy number variation with estrogen metabolism and human health.

Human cytosolic sulfotransferase 1A1 (SULT1A1) is considered to be one of the most important SULT isoforms for metabolism, detoxification, and carcinogenesis. This theory is driven by observations that SULT1A1 is widely expressed in multiple tissues and acts on a wide range of phenolic substrates. SULT1A1 is subject to functional common copy number variation (CNV) including deletions or duplications. However, it is less clear how SULT1A1 CNV impacts health and disease. To better understand the biological role of SULT1A1 in human health, we genotyped CNV in 14,275 Marshfield Clinic patients linked to an extensive electronic health record. Since SULT1A1 is linked to steroid metabolism, select serum steroid hormones were measured in 100 individuals with a wide spectrum of SULT1A1 CNV genotypes. Furthermore, comprehensive phenome-wide association studies (PheWAS) were conducted using diagnostic codes and clinical text data. For the first time, individuals homozygous null for SULT1A1 were identified in a human population. Thirty-six percent of the population carried >2 copies of SULT1A1 whereas 4% had ≤1 copy. Results indicate SULT1A1 CNV was negatively correlated with estrone-sulfate to estrone ratio predominantly in males (E1S/E1; p=0.03, r=-0.21) and may be associated with increased risk for common allergies. The effect of SULT1A1 CNV on circulating estrogen metabolites was opposite to the predicted CNV-metabolite trend based on enzymatic function. This finding, and the potential association with common allergies reported herein, warrants future studies.

The impact of music therapy versus music medicine on psychological outcomes and pain in cancer patients: a mixed methods study.

PURPOSE: The purpose of this study was to compare the impact of music therapy (MT) versus music medicine (MM) interventions on psychological outcomes and pain in cancer patients and to enhance understanding of patients' experiences of these two types of music interventions. METHODS: This study employed a mixed methods intervention design in which qualitative data were embedded within a randomized cross-over trial. Thirty-one adult cancer patients participated in two sessions that involved interactive music making with a music therapist (MT) and two sessions in which they listened to pre-recorded music without the presence of a therapist (MM). Before and after each session, participants reported on their mood, anxiety, relaxation, and pain by means of visual analogue and numeric rating scales. Thirty participants completed an exit interview. RESULTS: The quantitative data suggest that both interventions were equally effective in enhancing target outcomes. However, 77.4 % of participants expressed a preference for MT sessions. The qualitative data indicate that music improves symptom management, embodies hope for survival, and helps connect to a pre-illness self, but may also access memories of loss and trauma. MT sessions helped participants tap into inner resources such as playfulness and creativity. Interactive music making also allowed for emotional expression. Some participants preferred the familiarity and predictability of listening to pre-recorded music. CONCLUSIONS: The findings of this study advocate for the use of music in cancer care. Treatment benefits may depend on patient characteristics such as outlook on life and readiness to explore emotions related to the cancer experience.