Sutter Institute for Medical Research

With more women entering the medical workforce, caregiving challenges and family-work conflicts are of growing importance to today's neurologists. The aim of this study was to assess the impact of caregiver (CG) status on academic achievements in neurology, analyze the division of labor and time devoted to domestic responsibilities, and measure family-work conflict in US academic neurology faculty. A total of 19 US neurology departments completed a survey on baseline demographics, academic achievements, CG status, division of domestic time and labor, and responses on a FWC scale. Variables were assessed using independent samples t tests (or Mann-Whitney U for non-normally distributed data) and X2 analyses as appropriate, with CGs vs noncaregivers (N-CGs) serving as the independent groups. Women were twice as likely as men to categorize themselves as caregivers (p = 0.005). There were no significant differences in academic achievements between the CG and N-CG groups. However, CG men had a statistically significantly higher number of leadership positions (p = 0.022), number of publications as first or last author (p = 0.020), and number of awards (p = 0.004) when compared with CG women. The percentage of CG women faculty who reported spending more than 22 hours per week on child care was significantly higher than that of CG men (p = 0.003). Caregiver women also reported doing more work at home; taking care of children when they are sick; taking days off work when children are sick; handling more chores related to child care (e.g., managing activities/schedules); and doing laundry, cooking, and cleaning related to child care. Finally, the CG group experienced a higher level of FWC, as evidenced by responses on the FWC scale (p < 0.001). This finding was same for CG women compared with CG men (p = 0.034). Although the caregiving burden did not directly affect academic productivity, it significantly increased FWC in US academic neurology faculty surveyed. Female CG faculty disproportionately shouldered domestic and household responsibilities. Beyond recognizing CG challenges, advocating for a change in paradigm and providing solutions to these pervasive issues could be instrumental in preventing further attrition of professionals from our field, particularly women with caregiving roles.

Abstract Background: Multi-cancer early detection (MCED) tests are being established as a novel approach to screen for multiple cancer types with one test. A blood-based MCED test using cell-free DNA targeted methylation patterns to detect a shared cancer signal and predict a cancer signal origin (CSO) has demonstrated feasibility. An initial return of results study (PATHFINDER; NCT04241796) reported performance of a refined version of the MCED test, including a 43.1% positive predictive value (PPV), 98.5% negative predictive value (NPV), 99.5% specificity, and 88.0% CSO accuracy. To build on this work, the PATHFINDER 2 study (NCT05155605) will evaluate safety and performance of the MCED test in larger, more diverse populations. Methods: PATHFINDER 2 is a prospective, multicenter, interventional study. Participants ≥50 years of age will be enrolled, with specific targets to improve diversity (age, sex, race/ethnicity) and few exclusions due to comorbid conditions. Exclusion criteria include current clinical suspicion of cancer or recent cancer/treatment (within 3 years). Participants will undergo blood draw for MCED testing, followed by return of results (cancer signal detection and CSO) to the investigator and diagnostic evaluations if a cancer signal is detected. A confirmatory PET-CT scan will be performed when CSO-directed workups do not result in a cancer diagnosis. Participants will be followed for approximately 3 years. Primary endpoints include 1) MCED test safety in terms of diagnostic testing triggered by a positive result (number/type of procedures and adverse events) and 2) test performance (PPV, NPV, specificity, sensitivity, CSO accuracy, cancer detection rate and number needed to screen). Secondary endpoints include participant reported outcomes (eg, anxiety), utilization of guideline-recommended cancer screening, and cancer detection rate of confirmatory PET-CT, amongst others. The study plans to enroll approximately 35,000 participants across North America. Sites were selected based on geographic location, catchment area demographics, and practice setting (academic vs non-academic). Enrollment targets for age, sex and race/ethnicity (White [non-Hispanic] 72%; Hispanic or Latino 11%; African American or Black 11%; Asian, Native Hawaiian or Other Pacific Islander 6%; American Indian/Alaska Native 1%) were derived from US Census data. Strategies to promote diverse recruitment include translation of participant-facing documents across multiple languages, participant and healthcare provider educational material, and site-led community outreach campaigns. MCED testing is an emerging, potentially paradigm-changing strategy in cancer screening, and PATHFINDER 2 is designed to characterize the safety, performance, and clinical implementation of the MCED test as a screening tool in a broad and representative population. Citation Format: Karthik V. Giridhar, Michael J. Demeure, Raymond H. Kim, Justin A. Chen, Shirish Gadgeel, Dax Kurbegov, Margarita Lopatin, Roland Matthews, Marc Matrana, Charles McDonnell, Donald Richards, Benjamin Rybicki, Gretchen Stipec, Nima Nabavizadeh. PATHFINDER 2: A prospective study to evaluate safety and performance of a multi-cancer early detection test in a population setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4784.

Sutter Institute for Medical Research, Sacramento, California University of California, Davis, School of Medicine and the Sutter Institute for Medical Research, Sacramento, California Financial Disclosure The authors did not report any potential conflicts of interest.

Abstract Unlike most other viral pneumonitis, SARS-CoV-2 often causes hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. We questioned (1) if the severity of pneumonitis observed on lung ultrasound was associated with hospitalization and (2) could lung ultrasound be used to stratify which children needed blood tests?MethodsWe did a retrospective cross-sectional review of children aged between 14 days and 21 years of age being evaluated for Covid-19 in our pediatric emergency department from 30/November/2019 to 14/August/2021 who had had a point-of-care lung ultrasound. Lung ultrasounds were categorized using a 6-point ordinal scale. We used logistic regression to estimate the adjusted effect of lung ultrasound on hospital admission. We performed ordinary least square regression for the association between lung ultrasound severity and laboratory abnormalities. We adjusted these using propensity score derived inverse probability weighting to account for the non-random decision to obtain laboratory investigations.ResultsWe identified 500 point-of-care lung ultrasounds of which 427 could be assigned a severity category. Increasing lung ultrasound severity was associated with increased hospital admission OR 1.36(95% CI 1.08, 1.72.) Ferritin, LDH, transaminases, and D-dimer, but not CRP or troponin were significantly associated with more than moderately severe lung ultrasounds. D-Dimer, CRP, and troponin were sometimes elevated even when lung ultrasound was normal.ConclusionSeverity of pneumonitis was associated with hospital admission. Ferritin, LDH, transaminases, and D-dimer were increased in more than moderately severe pneumonitis but lung ultrasound did not predict elevation of other markers.

Le frottis sanguin est un étalement de sang sur une lame porte-objet qui permet la répartition régulière des cellules sanguines sur une seule épaisseur. Il devrait accompagner tout hémogramme chez les bovins. La réalisation d’un frottis de qualité nécessite : un prélèvement sanguin adéquat, un étalement et une coloration maitrisés.

Abstract • Background: Patients with acute low back pain frequently request diagnostic imaging, and clinicians feel pressure to acquiesce to such requests to sustain patient trust and satisfaction. Spinal imaging in patients with acute low back pain poses risks from diagnostic evaluation of false-positive findings, patient labeling and anxiety, and unnecessary treatment (including spinal surgery). Watchful waiting advice has been an effective strategy to reduce some low-value treatments, and some evidence suggests a watchful waiting approach would be acceptable to many patients requesting diagnostic tests. • Methods: We will use key informant interviews of clinicians and focus groups with primary care patients to refine a theory-informed standardized patient-based intervention designed to teach clinicians how to advise watchful waiting when patients request low-value spinal imaging for low back pain. We will test the effectiveness of the intervention in a cluster randomized clinical trial. We will recruit 8-10 primary care and urgent care clinics (~55 clinicians) in Sacramento, CA; clinicians will be randomized 1:1 to intervention and control groups. Over a 3 to 6 month period, clinicians in the intervention group will receive 3 visits with standardized patient instructors (SPIs) portraying patients with acute back pain; SPIs will instruct clinicians in a three-step model emphasizing establishing trust, empathic communication, and negotiation of a watchful waiting approach. Control physicians will receive no intervention. The primary outcome is the post-intervention rate of spinal imaging among actual patients with acute back pain seen by the clinicians adjusted for rate of imaging during a baseline period. Secondary outcomes are: use of targeted communication techniques during a follow-up visit with an SP; clinician self-reported use of watchful waiting with actual low back pain patients; post-intervention rates of diagnostic imaging for other musculoskeletal pain syndromes (to test for generalization of intervention effects beyond back pain); and patient trust and satisfaction with physicians. • Discussion: This trial will determine whether standardized patient instructors can help clinicians develop skill in negotiating a watchful waiting approach with patients with acute low back pain, thereby reducing rates of low-value spinal imaging. The trial will also examine the possibility that intervention effects generalize to other diagnostic tests. • Trial registration: NCT 04255199, ClinicalTrials.gov (January 20, 2020)

e24111 Background: Despite the fact that cannabis is still illegal in some states, two-thirds of all patients with cancer may have used cannabis at some point in their life to alleviate anorexia, nausea, chronic pain, and/or insomnia. Cannabis remains a Schedule 1 drug on the federal list with drugs such as heroin and LSD, which limits the ability to conduct quality clinical trials. This purpose of this study was to assess the prevalence, reasons for use, methods of use, and perceived benefits of medical cannabis in an adult community oncology clinic. Methods: Patients completed a questionnaire when they checked in for their appointment at the outpatient oncology clinic at Sutter Medical Center, Sacramento. Patients who used marijuana were asked questions regarding the mode of ingestion, perceived benefits, types of underlying cancer, and estimated monthly cost. Results: Of the 775 patients who completed the study to date, 129 men (29.3%) and 54 women (70.1%) responded that they used medical cannabis. Approximately 72% were white, 29.3% had breast cancer, and 13% had lung cancer. 39% percent had a diagnosis of metastatic cancer and 44% were undergoing chemotherapy. The most often stated reasons for use were pain (45%), sleep (43%), nausea (38%); and anxiety/mood (38%). Over 50% reported use of oils and tinctures and 44% used edibles. A smaller percentage preferred vaping (26%) or smoking (30%). Topical use was preferred by fewer patients (17%). Over 58% of patients stated they used more than one method. Most patients felt that use of cannabis helped alleviate symptoms. Marked improvement was reported by 40% patients; moderate improvement by another 41%. Only 13% users stated that they noted little to no improvement. The majority of patients (66%) spent $100 or less per month on marijuana whereas 22% spent between $100 and$200 per month. Conclusions: Medical cannabis is used by approximately one-fourth of all patients in an urban community cancer center in Northern California and the majority reported that cannabis provided improvements in symptoms associated with cancer and its treatment. Further research regarding mechanism of actions and associated risks is warranted.

Prior studies have demonstrated successful irritability treatment using dopaminergic antagonists in autistic patients. The purpose of this pilot study was to assess the effect of dextromethorphan/quinidine (DM/Q) in autistic adults (18-60years of age). This was a randomized, blinded, crossover, study of 14 patients randomized to DM/Q or a placebo for 8weeks, washed out for 4weeks, then crossed over to the opposite treatment. There were no serious adverse events. Subjects were significantly lower on the Aberrant Behavioral Checklist for Irritability (ABC-IR) (F1,10=7.42; p=0.021). Improvements in aggression and Clinical Global Impression were also seen. The findings suggest that DM/Q is well-tolerated and associated with improvements in irritability and aggression in adults with autism.

BackgroundStandard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma.MethodsAfter surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).ResultsFor the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone.ConclusionsAddition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival.Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1; initially registered 19 September 2002