Comparing gastrointestinal stromal tumor outcomes between geriatric and non-geriatric patients: A population-based analysis.

BACKGROUND: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients. METHODS: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery. RESULTS: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p < 0.0001). CONCLUSIONS: Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients.

Caring for Patients Requiring Venous Arterial Extracorporeal Membrane Oxygenation: Can Upstream Palliative Care Make a Difference?

OBJECTIVE: Palliative care consultation is relevant for patients requiring Venous-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO); however, evidence is limited to support its value. For this population, we compared length of stay (LOS) (primary outcome), operational metrics and goals of care (GOC) frequency before and after a collaboration between cardiothoracic (CT) surgery and Geriatrics and Palliative Medicine (GaP). METHODS: Retrospective chart review of patients (18+) admitted to a quaternary center that required VA-ECMO between 2019-2021 and received GaP consultation. Demographics, LOS, times to consult, illness severity, GOC, and outcomes were analyzed. RESULTS: 120 patients met inclusion criteria and 64 (53.3%) had GaP consultation. No differences were observed regarding demographics and insertion status (emergent vs elective). Median (IQR) days to GaP consult for 2019, 2020 and 2021 were 6.5 (4.0-14.5), 5.0 (2.0-11.0) and 3.0 (2.0-5.0), respectively (P = .006). Median days from insertion to consult for 2019, 2020 and 2021 were 6.0 (4.0-20.0), 3.0 (1.0-6.0) and 2.0 (1.0-4.0) (P = .003). Among survivors, over the 3-year course, median LOS was not statistically different. Between expired patients, median (IQR) LOS for 2019, 2020, and 2021 was 28.5 (23.0-40.0), 12.0 (8.0-14.0), 11.0 (5.0-17.0) days (P = .013). For patients not seen by GaP, 8 (14.3%) GOC notes were documented, compared with 42 (65.6%) for patients seen. Mortality was similar (53.6% vs 53.1% [GaP]). CONCLUSION: For patient on VA-ECMO, early GaP consultation may improve hospital LOS and GOC rates. We suggest organizations consider early palliative integration when instituting mechanical circulatory support.

Safety and Efficacy of Immune Checkpoint Inhibitors in Cancer Patients and Preexisting Autoimmune Disease: A Systematic Review and Meta-Analysis in Non-Small-Cell Lung Cancer.

BACKGROUND: Cancer patients with preexisting autoimmune diseases (AID) have been traditionally excluded from clinical trials of immune checkpoint inhibitors (ICI) due to concerns for toxicity. As indications for ICI expand, more data are needed on the safety and efficacy of ICI treatment in cancer patients with AID. METHODS: We systematically searched for studies consisting of NSCLC, AID, ICI, treatment response, and adverse events. Outcomes of interest include incidence of autoimmune flare, irAE, response rate, and ICI discontinuation. Study data were pooled using random-effects meta-analysis. RESULTS: Data were extracted from 24 cohort studies, consisting of 11,567 cancer patients (3774 NSCLC patients and 1157 with AID). Pooled analysis revealed an AID flare incidence of 36% (95% CI, 27%-46%) in all cancers and 23% (95% CI, 9%-40%) in NSCLC. Preexisting AID was associated with an increased risk of de novo irAE in all cancer patients (RR 1.38, 95% CI, 1.16-1.65) and NSCLC patients (RR 1.51, 95% CI, 1.12-2.03). There was no difference in de novo grade 3 to 4 irAE and tumor response between cancer patients with and without AID. However, in NSCLC patients, preexisting AID was associated with a 2-fold increased risk of de novo grade 3 to 4 irAE (RR 1.95, 95% CI, 1.01-3.75) but also better tumor response in achieving a complete or partial response (RR 1.56, 95% CI, 1.19-2.04). CONCLUSIONS: NSCLC patients with AID are at a higher risk of grade 3 to 4 irAE but are more likely to achieve treatment response. Prospective studies focused on optimizing immunotherapeutic strategies are needed to improve outcomes for NSCLC patients with AID.

Risk Factors for Postdischarge Major Thromboembolism and Mortality in Hospitalized Patients with COVID-19 with Cardiovascular Comorbidities: Insights from the CORE-19 Registry.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with venous and arterial thromboembolism (VTE and ATE) and all-cause mortality (ACM) in hospitalized patients. High-quality data are needed on postdischarge outcomes in patients with cardiovascular disease. OBJECTIVES: To analyze outcomes and identify risk factors for ATE, VTE, and ACM in a high-risk subgroup of hospitalized COVID-19 patients with baseline cardiovascular disease. METHODS: We investigated postdischarge rates and associated risk factors of ATE, VTE, and ACM in 608 hospitalized COVID-19 patients with coronary artery disease, carotid artery stenosis (CAS), peripheral arterial disease (PAD), or ischemic stroke. RESULTS: Through 90 days postdischarge, outcome rates were: ATE 27.3% (10.2% myocardial infarction, 10.1% ischemic stroke, 13.2% systemic embolism, 12.7% major adverse limb event); VTE 6.9% (4.1% deep vein thrombosis, 3.6% pulmonary embolism); composite of ATE, VTE, or ACM 35.2% (214/608). Multivariate analysis showed significant association between this composite endpoint and age >75 years (odds ratio [OR]: 1.90, 95% confidence interval [CI]: 1.22-2.94, p = 0.004), PAD (OR: 3.23, 95% CI: 1.80-5.81, p ≤ 0.0001), CAS (OR: 1.74, 95% CI: 1.11-2.75, p = 0.017), congestive heart failure (CHF) (OR: 1.84, 95% CI: 1.02-3.35, p = 0.044), previous VTE (OR: 3.08, 95% CI: 1.75-5.42, p < 0.0001), and intensive care unit (ICU) admission (OR: 2.93, 95% CI: 1.81-4.75, p < 0.0001). CONCLUSION: COVID-19 inpatients with cardiovascular disease experience high rates of ATE, VTE, or ACM through 90 days postdischarge. Age >75 years, PAD, CAS, CHF, previous VTE, and ICU admission are independent risk factors.

Patient Experience Performance at a Primary Cancer Center Versus Affiliated Community Facilities.

Purpose: Patient experience tools are used throughout health care to evaluate physician and departmental performance. In radiation medicine, these tools are important in evaluating patient-specific metrics throughout their care journey. This study compared patient experience outcomes from a central tertiary cancer program with network clinics in a health care network. Methods and Materials: Radiation medicine patient experience surveys (Press Ganey, LLC) were collected from a central facility and 5 network locations from January 2017 through June 2021. Surveys were distributed to patients after treatment completion. The study cohort was divided into the central facility and satellites. Questions were converted to a 0 to 100 scale from the Likert scale (1-5). To compare scores between site types, 2-way analysis of variance tests for the significance of sites adjusted for years of operations and adjustments for multiple comparisons (Dunnett's test) were completed on each question. Results: The number of consecutively returned surveys analyzed was 3777; a response rate of 33.3% was observed. The central site conducted 117,583 linear accelerator, 1425 Gamma Knife, 273 stereotactic radiosurgery, and 830 stereotactic body radiation therapy procedures. All satellites combined conducted 76,788 linear accelerator, 131 Gamma Knife, 95 stereotactic radiosurgery, and 355 stereotactic body radiation therapy procedures. The central facility fared better than the satellites on "Convenience of parking" (95.9 vs 87.9; P = .0001) but worse in other domains of care. Conclusions: All sites yielded exemplary patient experience rates. Community clinics scored higher than the main campus. The higher scores at the network sites require a deeper analysis of factors influencing the central facility, as the survey did not account for varying patient volumes and disparities in care complexity across sites. Attributes to satellites include lower patient volumes and easily navigable layouts. These results counter the impression that increased resources at the main campus create a better patient experience relative to network clinics and suggest that high-volume tertiary facilities will require unique initiatives to improve the patient experience.

A Retrospective Analysis of Three Focused Attention Meditation Techniques: Mantra, Breath, and External-Point Meditation.

Objective The goal of this study is to compare the effectiveness of three different meditation techniques (two internal focus techniques and one external focus technique) using a low-cost portable electroencephalography (EEG) device, namely, MUSE, for an objective comparison. Methods This is an IRB-approved retrospective study. All participants in the study were healthy adults. Each study participant (n = 34) was instructed to participate in three meditation sessions: mantra (internal), breath (internal), and external point. The MUSE brain-sensing headband (EEG) was used to document the "total time spent in the calm state" and the "total time spent in the calm or neutral state" (outcomes) in each three-minute session to conduct separate analyses for the meditation type. Separate generalized linear models (GLM) with unstructured covariance structures were used to examine the association between each outcome and the explanatory variable (meditation type). For all models, if there was a significant association between the outcome and the explanatory variable, pairwise comparisons were carried out using the Tukey-Kramer correction. Results The median time (in seconds) spent in the calm state while practicing mantra meditation was 131.5 (IQR: 94-168), while practicing breath meditation was 150 (IQR: 113-164), and while practicing external-point meditation was 100 (IQR: 62-126). Upon analysis, there was a significant association between the meditation type and the time spent in the calm state (p-value = 0.0006). Conclusion This is the first study comparing "internal" versus "external" meditation techniques using an objective measure. Our study shows the breath and mantra technique as superior to the external-point technique as regards time spent in the calm state. Additional research is needed using a combination of "EEG" and patient-reported surveys to compare various meditative practices. The findings from this study can help incorporate specific meditation practices in future mindfulness-based studies that are focused on healthcare settings and on impacting clinical outcomes, such as survival or disease outcomes.

Empirical likelihood confidence interval for sensitivity to the early disease stage.

Disease status can naturally be classified into three or more ordinal stages rather than just being binary stages. Many works have been done for the estimation and inference procedure regarding three ordinal disease stages, which are non-disease, early disease, and full disease stages. The early disease stage can be very important for therapeutic intervention and prevention potentiality. As a diagnostic measure, sensitivity to the early disease stage is often used. In this article, we propose confidence intervals for the sensitivity to early disease stage based on given target specificity for non-disease stage and target sensitivity to full disease stage using both empirical likelihood (EL) and adjusted EL procedures. We compare the performance of the proposed EL confidence intervals with other procedures in our simulation study. The proposed procedures are further applied to Alzheimer's Disease Neuroimaging Initiative data set.

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial.

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective: To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, Setting, and Participants: The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions: Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main Outcomes and Measures: The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Results: Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). Conclusions and Relevance: In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04401293.

In-Hospital 30-Day Survival Among Young Adults With Coronavirus Disease 2019: A Cohort Study.

BACKGROUND: Our objective was to characterize young adult patients hospitalized with coronavirus disease 2019 (COVID-19) and identify predictors of survival at 30 days. METHODS: This retrospective cohort study took place at 12 acute care hospitals in the New York City area. Patients aged 18-39 hospitalized with confirmed COVID-19 between March 1 and April 27, 2020 were included in the study. Demographic, clinical, and outcome data were extracted from electronic health record reports. RESULTS: A total of 1013 patients were included in the study (median age, 33 years; interquartile range [IQR], 28-36; 52% female). At the study end point, 940 (92.8%) patients were discharged alive, 18 (1.8%) remained hospitalized, 5 (0.5%) were transferred to another acute care facility, and 50 (4.9%) died. The most common comorbidities in hospitalized young adult patients were obesity (51.2%), diabetes mellitus (14.8%), and hypertension (13%). Multivariable analysis revealed that obesity (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.28-5.73; P = .002) and Charlson comorbidity index score (aHR, 1.20; 95% CI, 1.07-1.35; P = .002) were independent predictors of in-hospital 30-day mortality. CONCLUSIONS: Obesity was identified as the strongest negative predictor of 30-day in-hospital survival in young adults with COVID-19.

Treatment-Dose LMWH versus Prophylactic/Intermediate Dose Heparins in High-Risk COVID-19 Inpatients: Rationale and Design of the HEP-COVID Trial.

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15-30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.