Multiplexed Serum Biomarkers to Discriminate Nonviable and Ectopic Pregnancy.

OBJECTIVE: The use of multiplexed biomarkers may improve the diagnosis of normal and abnormal early pregnancies. In this study we assessed 24 markers with multiple machine learning-based methodologies to evaluate combinations of top candidates to develop a multiplexed prediction model for identification of 1) viability and 2) location of an early pregnancy. DESIGN: A nested case-control design evaluating the predictive ability and discrimination of biomarkers in patients at risk of early pregnancy failure in the first trimester to classify viability and location SUBJECTS: 218 individuals with a symptomatic (pain and/or bleeding) early pregnancy: 75 with an ongoing intrauterine gestation, 68 ectopic pregnancies, and 75 miscarriages. INTERVENTIONS: Serum values of 24 biomarkers were assessed in the same patients. Multiple machine learning-based methodologies to evaluate combinations of these top candidates to develop a multiplexed prediction model for identification of 1) a nonviable pregnancy (ongoing intrauterine pregnancy vs miscarriage or ectopic pregnancy) and 2) an ectopic pregnancy (ectopic pregnancy vs ongoing intrauterine pregnancy or miscarriage). MAIN OUTCOME MEASURES: The predicted classification by each model was compared to actual diagnosis and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), conclusive classification, and accuracy were calculated. RESULTS: Models using classification regression tree analysis using three markers (PSG3, CG-Alpha and PAPPA) were able to predict a maximum sensitivity 93.3%, a maximum specificity 98.6%. The model with the highest accuracy was 97.4% (with 70.2% receiving classification). Models using an overlapping group of three markers (sFLT, PSG3 and TFP12) achieved a maximum sensitivity of 98.5%. and a maximum specificity of 95.3%. The model with the highest accuracy was 94.4% (with 65.6% receiving classification). When the models were used simultaneously the conclusive classification increased to 72.7% with an accuracy 95.9%. The predictive ability of the biomarkers random forest produced similar test characteristics when using 11 predictive markers. CONCLUSION: We have demonstrated a pool of biomarkers from divergent biological pathways that can be used to classify individuals with potential early pregnancy loss. The biomarkers CG-Alpha, PAPPA and PSG3 can be used to predict viability and sFLT, TPFI2 and PSG3 can be used to predict pregnancy location.

Trajectories and predictors of high-occurrence pain flares in ambulatory cancer patients on opioids.

BACKGROUND: Pain flares have a substantive impact on the quality of life and well-being of patients with cancer. We identified longitudinal trajectories (clusters) of cancer pain flares in ambulatory patients and sociodemographic and clinical predictors of these trajectories. METHODS: In a prospective cohort study using ecological momentary assessment (mEMA), we collected patient-reported daily pain flare ratings data over 5 months and identified predictors and correlates using validated measures. RESULTS: The mean age of the sample (N = 270) was 60.9 years (SD = 11.2), 64.8% were female, and 32.6% self-identified as African American. Four pain flare clusters were identified. The "high-occurrence" cluster (23% of patients) experienced 5.5 (SD = 5.47) daily flares, whereas low-moderate clusters (77%) reported 2.4 (SD = 2.74) daily flares (P < .000). Those in the high-occurrence cluster reported higher pain scores (P = .000), increased pain-related interference (P = .000), depressive symptoms (P = .023), lower quality of life (P = .001), and reduced pain self-efficacy (P = .006). Notably, 67.2% of those prescribed opioids as needed (PRN only) were in the high-occurrence pain flare cluster, compared with 27.9% with PRN and around-the-clock opioid prescriptions (P = .024). Individual predictors of high-occurrence pain flares were income below $30 000, unemployment, being African American, lower education level, Medicaid insurance, current opioid misuse (COMM), baseline inpatient hospital stay duration, and PRN-only opioid regimen. In the multiple predictor model, lower education level, unemployment, COMM score, extended inpatient duration, and PRN-only opioid regimen remained significant. CONCLUSION: In ambulatory patients with cancer, high occurrence of pain flares may be mitigated by attention to opioid prescription factors and addressing social determinants of health needs of underserved patients.

Percutaneous Management of Dialysis Access Steal Syndrome: Interventions and Outcomes from a Single Institution's 20-Year Experience.

PURPOSE: To determine safety and effectiveness of percutaneous interventions performed by interventional radiologists at a single institution over 2 decades in patients with dialysis access steal syndrome (DASS). MATERIALS AND METHODS: A retrospective review of fistulograms from 2001 to 2021 (N = 11,658) was performed. In total, 286 fistulograms in 212 patients with surgically created dialysis accesses met inclusion criterion of fistulography for suspected DASS. Chart review collected data regarding patient demographics, comorbidities, access characteristics, fistulography findings, intervention(s) performed, and outcomes. Procedures with and without DASS intervention were compared. Odds ratios (ORs), adjusted for age, sex, comorbidities, access characteristics, and multiple within-patient events, were calculated using logistic regression to determine associations between steal intervention status and outcome variables: (a) major adverse events, (b) access preservation, and (c) follow-up surgery. A percutaneously treatable cause of DASS was present in 128 cases (45%). Treatment of DASS lesions was performed in 118 cases. Fifteen embolizations were also performed in patients without DASS lesions. RESULTS: Technical success of DASS interventions, defined by the Society of Interventional Radiology (SIR) reporting standards, was 94%; 54% of interventions resulted in DASS symptom improvement at a median follow-up of 15 days. Patients with steal intervention had 60% lower odds of follow-up surgery (OR, 0.4; P = .007). There was no difference in major adverse events (P = .98) or access preservation (P = .13) between groups. CONCLUSIONS: In this retrospective cohort study, approximately half of DASS fistulograms revealed a percutaneously treatable cause of steal. Over half of DASS interventions resulted in symptomatic relief. Percutaneous intervention was associated with lower odds of follow-up surgery without compromising access preservation.

Salivary Diurnal Cortisol Predicts Post-Traumatic Stress Symptoms in Parents of Infants With Congenital Heart Disease.

BACKGROUND: Parents of infants born with congenital heart disease (CHD) who require open heart surgery after birth are at risk for prolonged psychological distress. Even after their infants are discharged, parents may experience anxiety, depressive, and post-traumatic stress (PTS) symptoms; yet, it is unclear which parents are at greater risk for ongoing symptoms. The purpose of this study was to explore whether measures of the biomarker cortisol in parents during their infants' postoperative period were associated with subsequent psychological distress symptoms at three-month post discharge. METHODS: This was a prospective, longitudinal exploratory study of 40 parents of infants with CHD after open heart surgery using consecutive enrollment. Parents provided diurnal saliva samples for two consecutive days in the postoperative period. Six predictors were summarized and generated including waking cortisol, bedtime cortisol, cortisol awaking response, area under curve with respect to the ground (AUCg), cortisol index, and cortisol slope. Self-report outcome measures on anxiety, depressive, and PTS symptoms were collected three-months post-discharge. Linear mixed models examined the associations between each predictor and each outcome while accounting for within-dyad variance using an unstructured covariance matrix. RESULTS: Cortisol AUCg was a predictor of PTS at three-months post-discharge (ß = .34, p = .03, Cohen's d = 2.05). No significant relationships were found with the other cortisol measures. CONCLUSIONS & IMPLICATIONS: Findings suggest that cortisol area under curve may help to identify parents at risk for increased PTS in the months following their infants' hospitalization for cardiac surgery, serving as a foundation for future study in this area.

Better Nurse Practitioner Primary Care Practice Environments Reduce Hospitalization Disparities Among Dually-Enrolled Patients.

BACKGROUND: Over 12 million Americans are dually enrolled in Medicare and Medicaid. These individuals experience over twice as many hospitalizations for chronic diseases such as coronary artery disease and diabetes compared with Medicare-only patients. Nurse practitioners (NPs) are well-positioned to address the care needs of dually-enrolled patients, yet NPs often work in unsupportive clinical practice environments. The purpose of this study was to examine the association between the NP primary care practice environment and hospitalization disparities between dually-enrolled and Medicare-only patients with chronic diseases. METHODS: Using secondary cross-sectional data from the Nurse Practitioner Primary Care Organizational Climate Questionnaire and Medicare claims files, we examined 135,648 patients with coronary artery disease and/or diabetes (20.0% dually-eligible, 80.0% Medicare-only), cared for in 450 practices employing NPs across 4 states (PA, NJ, CA, FL) in 2015. We compared dually-enrolled patients' odds of being hospitalized when cared for in practice environments characterized as poor, mixed, and good based on practice-level Nurse Practitioner Primary Care Organizational Climate Questionnaire scores. RESULTS: After adjusting for patient and practice characteristics, dually-enrolled patients in poor practice environments had the highest odds of being hospitalized compared with their Medicare-only counterparts [odds ratio (OR): 1.48, CI: 1.37, 1.60]. In mixed environments, dually-enrolled patients had 27% higher odds of a hospitalization (OR: 1.27, CI: 1.12, 1.45). However, in the best practice environments, hospitalization differences were nonsignificant (OR: 1.02, CI: 0.85, 1.23). CONCLUSIONS: As policymakers look to improve outcomes for dually-enrolled patients, addressing a modifiable aspect of care delivery in NPs' clinical practice environment is a key opportunity to reduce hospitalization disparities.

Impact of Atrial Fibrillation on Heart Failure in Patients Treated With Anthracycline Chemotherapy.

Atrial fibrillation (AF) and anthracyclines are known risk factors for heart failure (HF). The magnitude of the effect of preexisting AF (preanthracycline AF) and newly developed AF (postanthracycline AF) in patients treated with anthracyclines on the occurrence of HF is unknown. The aim of our study was to characterize the impact of preanthracycline and postanthracycline AF on the subsequent occurrence of HF in patients treated with anthracyclines. In 5,598 patients treated with new anthracycline therapy at a tertiary center between 2008 and 2021, propensity score matching was used to match 204 pairs with or without preanthracycline AF and 135 pairs with or without postanthracycline AF. The primary outcome was new-onset symptomatic HF defined by the American Heart Association/American College of Cardiology guidelines. Patients with and without preanthracycline and postanthracycline AF were well matched for age, gender, medications, and cardiovascular risk factors. A total of 45 patients with preanthracycline AF and 23 matched patients developed HF (5-year cumulative incidence: 29% in the preanthracycline AF group and 13% in the matched group, p = 0.003; hazard ratio 2.1, 95% confidence interval 1.3 to 3.4, p = 0.004). A total of 161 patients (2.9%) developed postanthracycline AF. A total of 39 patients (5-year cumulative incidence: 40%) with postanthracycline AF and 9 matched patients (5-year cumulative incidence: 7%) developed HF (hazard ratio 6.1, 95% confidence interval 3.0 to 12.4, p <0.001). Preanthracycline AF and postanthracycline AF are associated with a high incidence of subsequent HF in patients treated with anthracyclines. Prospective studies of therapies are required to decrease HF in these high-risk patients.

Mental Health Symptoms in Parents of Infants 3 Months After Discharge Following Neonatal Cardiac Surgery.

BACKGROUND: Parents of newborns with congenital heart disease (CHD) are at risk for anxiety, depression, and post-traumatic stress. Few studies have examined whether modifiable factors that influence parents' mental health after discharge are present during postoperative care in the pediatric cardiac intensive care unit (PCICU). OBJECTIVE: To describe mental health symptoms of parents of infants with CHD 3 months after PCICU discharge and to determine factors during the PCICU stay that are predictors of such symptoms. METHODS: A longitudinal cohort pilot study of 56 parents (28 mother-father dyads) of 28 infants with CHD. During the first postoperative week after cardiac surgery, parents completed questionnaires measuring factors potentially influencing mental health. Three months after discharge, 42 parents of 22 infants completed validated measures of anxiety, depression, and posttraumatic stress. RESULTS: Three months after discharge, 26% of parents had clinically elevated levels of anxiety symptoms, 21% had clinically significant levels of depressive symptoms, and 19% had posttraumatic stress symptoms. In multi-variable analysis, parental role alteration in the PCICU was predictive of anxiety (P = .002), depressive (P = .02), and posttraumatic stress (P = .02) symptoms 3 months after discharge. Higher education level was predictive of anxiety symptoms (P = .009). Postnatal CHD diagnosis was predictive of posttraumatic stress symptoms (P = .04). CONCLUSIONS: Parental role alteration perceived by parents during the PCICU stay is a modifiable stressor contributing to adverse mental health symptoms 3 months after discharge. Interventions targeting parental role alteration in the PCICU are critically needed.

The Association of Metformin With Heart Failure in Patients With Diabetes Mellitus Receiving Anthracycline Chemotherapy.

Background: The prevention of heart failure (HF) is an important issue in patients treated with anthracyclines. Metformin, widely used to treat diabetes mellitus (DM), protects from anthracycline-induced cardiotoxicity in vitro and in animal models. Objectives: The aim of our study was to test the association of metformin with the occurrence of symptomatic HF in patients with DM receiving anthracyclines. Methods: A total of 561 patients with DM received new anthracycline therapy between 2008 and 2021 in a tertiary care center; propensity score matching was used to compare patients with or without metformin treatment. The primary outcome was new onset symptomatic HF occurring within 1 year of the initiation of anthracyclines. Results: A total of 315 patients (65 ± 11 years of age, 33.7% male) were included. Patients with and without metformin were well matched for age, sex, type of cancer, medications, and cardiovascular risk factors. Six patients treated with metformin and 17 matched patients developed HF within 1 year of anthracycline initiation. The incidence of HF in patients treated with metformin was lower than patients without metformin within 1 year after anthracyclines (cumulative incidence: 3.6% vs 10.5%; P = 0.022; HR: 0.35; 95% CI: 0.14-0.90; P = 0.029). The use of metformin (HR: 0.71; 95% CI: 0.50-1.00; P = 0.049), was also associated with lower mortality. Conclusions: The use of metformin was associated with a lower incidence of HF and overall mortality in patients with DM receiving anthracyclines. Our findings should be further confirmed by randomized control trials.

Evaluating Consistency of Documented ICD Codes for Hospitalized Patients With Sickle Cell Disease.

OBJECTIVES: Conducting health services research relies on consistent diagnosis code documentation; however, it is unknown if consistent documentation in claims data occurs among patients with sickle cell disease (SCD) and/or trait (SCT). The objective of this study was to examine the consistency of International Classification of Diseases (ICD) code documentation for SCD/SCT and identify coding discrepancies between patients' hospitalizations. PATIENTS: A total of 80 031 hospitalization records across 528 hospitals belonging to 15 380 unique patients who had at least 1 documentation of SCD/SCT and 2 or more hospitalizations during the study period (April 2015-December 2016). METHODS: Secondary analysis of patient discharge abstracts in California, Florida, New Jersey, and Pennsylvania. ICD 9 and ICD 10 codes identified patients with SCD/SCT. Variations in documentation consistency across hospitals were examined. RESULTS: Only 51% of patients were consistently documented. There were statistically significant differences in whether a patient was or was not consistently documented based on: age, race/ethnicity, sex, insurer, and disease type. Twenty-five percent of hospitalization records were not consistently documented with an SCD code. Hospitalization records, for patients not consistently documented (49%), often included primary admitting diagnoses for conditions associated with SCD. Few hospitals (18%) were above average in consistently documenting SCD/SCT. CONCLUSIONS: Not consistent documentation for SCD/SCT occurs with variation among patients and across disease type and hospitals. These findings signal to researchers the importance of thoroughly identifying all hospitalizations when studying populations with chronic disease. Without accurate documentation, research relying on claims data may produce inaccurate findings.

Telehealth utilization in gynecologic oncology clinical trials.

OBJECTIVE: Prior to the COVID-19 pandemic, telehealth visits and remote clinical trial operations (such as local collection of laboratory tests or imaging studies) were underutilized in gynecologic oncology clinical trials. Current literature on these operational changes provides anecdotal experience and expert opinion with few studies describing patient-level safety data. We aimed to evaluate the safety and feasibility of telehealth and remote clinical trial operations during the COVID-19 Pandemic. METHODS: Gynecologic oncology patients enrolled and actively receiving treatment on a clinical trial at a single, academic institution during the designated pre-Telehealth and Telehealth periods were identified. Patients with at least 1 provider or research coordinator telehealth visit were included. Patient demographics, health system encounters, adverse events, and protocol deviations were collected. Pairwise comparisons were performed between the pre-Telehealth and Telehealth period with each patient serving as their own control. RESULTS: Thirty-one patients met inclusion criteria. Virtual provider visits and off-site laboratory testing increased during the Telehealth period. Delays in provider visits, imaging, and laboratory testing did not differ between time periods. Total and minor protocol deviations increased in incidence during the Telehealth period and were due to documentation of telehealth and deferment of non-therapeutic testing. Major protocol deviations, emergency department visits, admissions, and severe adverse events were of low incidence and did not differ between time periods. CONCLUSIONS: Telehealth and remote clinical trial operations appeared safe and did not compromise clinical trial protocols in a small, single institutional study. Larger scale evaluations of such trial adaptations should be performed to determine continued utility following the Pandemic.

Anesthesia and Sedation Exposure and Neurodevelopmental Outcomes in Infants Undergoing Congenital Cardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Children undergoing complex cardiac surgery are exposed to substantial cumulative doses of sedative medications and volatile anesthetics and are more frequently anesthetized with ketamine, compared with healthy children. This study hypothesized that greater exposure to sedation and anesthesia in this population is associated with lower neurodevelopmental scores at 18 months of age. METHODS: A secondary analysis was conducted of infants with congenital heart disease who participated in a prospective observational study of environmental exposures and neurodevelopmental outcomes to assess the impact of cumulative volatile anesthetic agents and sedative medications. Cumulative minimum alveolar concentration hours of exposure to volatile anesthetic agents and all operating room and intensive care unit exposures to sedative and anesthesia medications were collected before administration of Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley III), at 18 months of age. RESULTS: The study cohort included 41 (37%) single-ventricle and 69 (63%) two-ventricle patients. Exposures to volatile anesthetic agents, opioids, benzodiazepines, and dexmedetomidine were not associated with abnormal Bayley III scores. At 18-month follow-up, after adjusting for confounders, each mg/kg increase in ketamine exposure was associated with a 0.34 (95% CI, -0.64 to -0.05) point decrease in Bayley III motor scores (P = 0.024). CONCLUSIONS: Total cumulative exposures to volatile anesthetic agents were not associated with neurodevelopmental impairment in infants with congenital heart disease undergoing various imaging studies and procedures, whereas higher ketamine doses were associated with poorer motor performance.

Development of the perceived miscommunication measure in the pediatric intensive care unit.

PURPOSE: Miscommunication between parents and healthcare providers in the Pediatric Intensive Care Unit (PICU) can affect family-provider relationships and outcomes. This paper reports on the development and psychometric testing of a measure for parent perceived miscommunication, defined as the failure to communicate clearly as perceived by relevant stakeholders in the PICU. DESIGN AND METHODS: Miscommunication items were identified through a review of the literature with interdisciplinary experts. In a cross-sectional quantitative survey, the scale was tested with 200 parents of children discharged from a PICU at a large Northeastern Level 1 Pediatric hospital. The psychometric properties of a 6-item miscommunication measure were assessed using exploratory factor analysis and internal consistency reliability. RESULTS: Exploratory factor analysis yielded one factor explaining 66.09% of the variance. Internal consistency reliability in the PICU sample was α = 0.89. As hypothesized, there was a significant correlation between parental stress, trust, and perceived miscommunication in the PICU (p < .001). Confirmatory factor analysis supported good fit indices in testing the measurement model (χ2/df = 2.57, Goodness of Fit Index (GFI) = 0.979, Confirmatory Fit Index (CFI) =0.993 and Standardized Mean Residual (SMR) = 0.0136). CONCLUSIONS: This new six-item miscommunication measure shows promising psychometric properties including content and construct validity, which can be further tested and refined in future studies of miscommunication and outcomes in PICU. PRACTICE IMPLICATIONS: Awareness of perceived miscommunication in the PICU can benefit stakeholders within the clinical environment by recognizing the importance of clear and effective communication and how language affects the parent-child-provider relationship.

Comparison of Transthoracic Contrast Echocardiography with High-Resolution Chest CT after Embolization of Pulmonary Arteriovenous Malformation.

PURPOSE: To compare postembolotherapy follow-up graded transthoracic contrast echocardiography (TTCE) and high-resolution computed tomography (CT) of the chest and to evaluate the use of graded TTCE in the early postembolic period. MATERIALS AND METHODS: Thirty-five patients (6 men and 29 women; mean age, 56 years; range, 27-78 years) presenting for postembolotherapy follow-up between 2017 and 2021 with concurrent high-resolution CT and graded TTCE were analyzed retrospectively. Untreated pulmonary arteriovenous malformations (PAVMs) with a feeding artery of ≥2 mm were considered treatable. RESULTS: Ninety-four percent of patients (33 of 35) did not have treatable PAVMs on high-resolution CT. TTCE was negative for shunts (Grade 0) in 34% of patients (n = 12). Of patients with a TTCE positive for shunts (23 of 35, 66%), 83% had a Grade 1 shunt, 13% had a Grade 2 shunt, and 4% had a Grade 3 shunt. No patient with a Grade 0 or 1 shunt had a treatable PAVM on high-resolution CT. Of the 2 patients with PAVMs requiring treatment, one had a Grade 2 shunt and one had a Grade 3 shunt. TTCE grade was significantly associated with the presence of a treatable PAVM on high-resolution CT (P < .01). CONCLUSIONS: Graded TTCE predicts the need for repeat embolotherapy and does so reliably in the early postembolotherapy period. This suggests that graded TTCE can be utilized in the postembolotherapy period for surveillance, which has the potential to lead to a decrease in cumulative radiation in this patient population.

Patient Experience of Photobiomodulation Therapy in Head and Neck Chronic Lymphedema.

Purpose: Lymphedema is a common late effect of head and neck cancer treatment that causes various symptoms, functional impairment, and poor quality of life. We completed a pilot, prospective, single-arm clinical trial to determine the feasibility and potential efficacy of the use of photobiomodulation (PBM) therapy for head and neck lymphedema. In this study, we report patients' perceived treatment experience of PBM therapy and provide suggestions to better understand head and neck cancer survivors' experience of PBM therapy. Methods: Head and neck cancer patients who underwent PBM therapy completed face-to-face semi-structured interviews. Interviews were audio-recorded and then transcribed verbatim. Qualitative content analysis was used to analyze the transcriptions from the interviews. Results: Among 12 participants who consented for the study, 11 (91.7%) completed the PBM therapy. Participants described positive experiences and unique benefits about the PBM therapy, for example, decreased swelling, reduced tightness, increased range of motion, increased saliva production, and improved ability to swallow. Some participants (n = 5, 45.5%) delineated challenges related to traffic, travel time, and distance from study location. Many participants proposed suggestions for future research on PBM therapy, for example, research on internal edema and its relationship with swallowing, and indicated patients with severe lymphedema and fibrosis may be more likely to benefit. Conclusions: Findings from this study suggested the potential benefits of PBM therapy in treatment of chronic head and neck lymphedema. Rigorously designed clinical trials are needed to evaluate the effect of PBM therapy for head and neck cancer-related lymphedema. Trial Registration Number and Date of Registration: ClinicalTrials.gov Identifier: NCT03738332; date of registration: November 13, 2018.

Effects of a mobile health nutrition intervention on dietary intake in children who have autism spectrum disorder.

Background: Children who have Autism Spectrum Disorder (ASD) show preferences for processed foods, such as salty and sugary snacks (SSS) and sugar-sweetened beverages (SSB), while healthier foods, such as fruits and vegetables (FV), are consumed less. Innovative tools are needed that can efficiently disseminate evidence-based interventions and engage autistic children to improve their diet. Aim: The aim of this 3-month randomized trial was to test the initial efficacy of a mobile health (mHealth) nutrition intervention on changing consumption of targeted healthy (FV) and less healthy foods/beverages (SSS, SSB) in children who have ASD, ages 6-10, who were picky eaters. Methods: Thirty-eight parent-child dyads were randomly assigned to either an intervention (technology) group or a wait list control (education) group. The intervention included behavioral skills training, a high level of personalization for dietary goals, and involved parents as "agents of change." Parents in the education group received general nutrition education and the dietary goals but did not receive skills training. Children's intake was assessed at baseline and at 3 months using 24-hour dietary recalls. Results: While there were no significant group-by-time interactions (P > 0.25) for any of the primary outcomes, we found a significant main effect of time for FV intake (P = 0.04) indicating that both groups consumed more FV at 3 months (2.58 ± 0.30 servings/day) than at baseline (2.17 ± 0.28 servings/day; P = 0.03). Children in the intervention group who consumed few FV at baseline and showed high engagement with the technology increased their FV intake by 1.5 servings/day (P < 0.01). Children's taste/smell sensitivity significantly predicted their FV intake (P = 0.0446); for each unit of lower taste/smell sensitivity (indicating greater sensory processing abnormalities), FV intake increased by 0.13 ± 0.1 servings/day. Discussion: This mHealth intervention did not yield significant between-group differences for changing consumption of targeted foods/beverages. Only children who consumed few FV at baseline and highly engaged with the technology increased their FV intake at 3 months. Future research should test additional strategies to expand the intervention's impact on a wider range of foods while also reaching a broader group of children who have ASD. This trial was registered at clinicaltrials.gov as NCT03424811.Clinical Trial Registration: This study was registered at clinicaltrials.gov as NCT03424811.

Don't Throw the Baby Out With the Bathwater: Meta-Analysis of Advance Care Planning and End-of-life Cancer Care.

CONTEXT: There is ongoing discourse about the impact of advance care planning (ACP) on end-of-life (EOL) care. No meta-analysis exists to clarify ACP's impact on patients with cancer. OBJECTIVE: To investigate the association between, and moderators of, ACP and aggressive vs. comfort-focused EOL care outcomes among patients with cancer. METHODS: Five databases were searched for peer-reviewed observational/experimental ACP-specific studies that were published between 1990-2022 that focused on samples of patients with cancer. Odds ratios were pooled to estimate overall effects using inverse variance weighting. RESULTS: Of 8,673 articles, 21 met criteria, representing 33,541 participants and 68 effect sizes (54 aggressive, 14 comfort-focused). ACP was associated with significantly lower odds of chemotherapy, intensive care, hospital admissions, hospice use fewer than seven days, hospital death, and aggressive care composite measures. ACP was associated with 1.51 times greater odds of do-not-resuscitate orders. Other outcomes-cardiopulmonary resuscitation, emergency department admissions, mechanical ventilation, and hospice use-were not impacted. Tests of moderation revealed that the communication components of ACP produced greater reductions in the odds of hospital admissions compared to other components of ACP (e.g., documents); and, observational studies, not experimental, produced greater odds of hospice use. CONCLUSION: This meta-analysis demonstrated mixed evidence of the association between ACP and EOL cancer care, where tests of moderation suggested that the communication components of ACP carry more weight in influencing outcomes. Further disease-specific efforts to clarify models and components of ACP that work and matter to patients and caregivers will advance the field.

Nurse, Provider, and Emergency Department Technician: Perceptions and Experiences of Violence and Aggression in the Emergency Department.

INTRODUCTION: Patient/visitor violence and aggression (V&A) in the emergency department occurs daily. Few interventions exist to decrease V&A. Research describing prevalence, severity, and perceived safety among ED clinicians is limited. METHODS: A descriptive survey explored V&A against ED clinicians in one urban emergency department. A sample of nurses, ED technicians, physicians and advanced practice providers participated. Participants completed a demographic survey, Personal Workplace Safety Instrument for Emergency Nurses (PWSI-EN), and ENA V&A frequency checklist. Analysis of Variance (ANOVA) for unadjusted and Analysis of Covariance (ANCOVA) for adjusted associations were used to assess differences in the PWSI-EN survey composite score and "feeling safe in the ED" among ED roles. ANCOVA was adjusted for potential confounders: sex, race, years working in emergency department, and shift worked. RESULTS: Sixty-five (46.4%) of the 140 ED clinicians returned surveys, which were almost evenly distributed between ED clinician roles and sex. Mean age was 37.2 (range: 21-64) years. All (100%) nurses and providers reported being verbally abused. More nurses reported physical violence (n = 21, 87.5%) than providers (n = 7, 36.8%) and ED technicians (n = 11, 55%). Nurses and ED technicians reported experiencing greater prevalence of physical violence than providers (P < .05). Nurses (mean 3.29, range 2.95 to 3.63) were more fearful for their personal safety than ED technicians (mean 3.88, range 3.48 to 4.28) (P < .03). DISCUSSION: V&A are common creating a fearful environment. However, little research regarding clinician perceptions exists. Our study aids in identifying areas for clinician-targeted strategies to prevent ED V&A.

Incidence of MACE in Patients Treated With CAR-T Cell Therapy: A Prospective Study.

Background: Previous retrospective studies have shown that chimeric antigen receptor T (CAR-T) cell therapy may be associated with major adverse cardiovascular events (MACE), especially in the context of cytokine-release syndrome (CRS) events. Objectives: The aim of this prospective observational study was to define the occurrence of MACE in adults undergoing treatment with CAR-T cell therapy and identify associated risk factors. Methods: Vital signs, blood samples, and an echocardiogram were collected prior to and 2 days, 1 week, 1 month, and 6 months after CAR-T cell infusion, and charts were consulted at 12 months. In the event of CRS, echocardiography was repeated within 72 hours. MACE were defined as cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke, and de novo cardiac arrhythmia. Results: A total of 44 patients were enrolled (mean age 58 ± 11 years, 77% men). The median follow-up duration was 487 days (Q1-Q3: 258-622 days). There were 24 episodes of CRS in 23 patients (52%) (13 grade 1, 10 grade 2, and 1 grade 3), with a median time to CRS of 4 days. Two patients had MACE (heart failure with preserved ejection fraction and atrial fibrillation) within 1 year and 6 and 7 days after CAR-T cell infusion. There was no change in left ventricular ejection fraction, but a modest decrease in global longitudinal strain was noted. Conclusions: There were few cardiac effects associated with contemporary CAR-T cell therapy. As MACE occurred after CRS episodes, aggressive treatment and close follow-up during CRS events are essential.

A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m2 and 102 (15%) had diabetes. Death occurred in 41 participants. Compared with placebo, fenofibrate had no effect on the primary endpoint. The median (interquartile range) rank in the placebo arm was 347 (172, 453) versus 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in secondary and exploratory endpoints, including all-cause death, across arms. There were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group. Overall, among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes ( NCT04517396 ).

A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019.

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro . Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m 2 , and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.