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The CONSORT guideline defines a pilot trial as a small-scale version of a desired future efficacy trial that is intended to answer the key questions of whether and how a larger study should be done. For example, a pilot trial might evaluate different approaches to data collection or outcome measurement. However, pilot trials are unreliable for assessing treatment efficacy due to the statistical phenomenon called sampling variability. In this tutorial we use computer simulation to demonstrate the influence of sampling variability on efficacy estimates from pilot trials, illustrating why pilot trial designs should not be used to evaluate whether a treatment is promising or not. We simulate a 2-arm parallel group trial (N=20 per group) with a survival outcome as an example. Simulations are done under two scenarios: 1) the treatment is efficacious at the level of a hypothetical minimum clinically important difference (hazard ratio [HR] = 0.75); and 2) the treatment is not efficacious (HR=1). As expected, in both simulated scenarios the range of observed results is distributed around the true treatment effect, HR=0.75 or HR=1. Importantly, ∼20% of trials simulated under scenario 1 incorrectly suggest the treatment may be harmful (HR > 1). Under scenario 2, half of the simulated studies incorrectly suggest the treatment is beneficial. Treatment effect estimates from pilot trials should not be used to make future development decisions regarding a novel therapy because of the high risk of misleading conclusions. [ABSTRACT FROM AUTHOR]

Purpose: Psychological distress is prevalent in Hodgkin lymphoma (HL). Many patients, regardless of prognosis, receive ABVD chemotherapy as first-line treatment, but few studies have specifically examined the nature of distress during this shared treatment experience. Methods: We conducted a retrospective study of patient-reported distress in HL patients receiving ABVD treatment at a single tertiary care facility. Distress was measured using the National Comprehensive Cancer Network Distress Thermometer and Problem List (PL). We used descriptive statistics and generalized estimating equations to assess the prevalence of distress and specific problem items during treatment and associations with patient- and disease-related factors. Results: We collected data from 50 patients comprising 467 unique encounters, with 369/467 (79.0%) reporting a distress thermometer score. Median distress score was 2 (IQR: 0–5), but actionable distress (distress thermometer ≥4) was noted for 118/369 (32.0%) encounters. Actionable distress was only related to having a prior cancer, which conferred lower odds of actionable distress (OR 0.23, 95% CI 0.07–0.74, p=0.01) Physical and emotional problems were reported for 287/369 (77.8%) and 125/369 (33.9%) visits, respectively. Female patients had greater odds of both physical (OR 3.17, 95% CI 1.32–7.66, p=0.01) and emotional (OR 3.31, 95% CI 1.25–8.73, p=0.02) problems. Conclusion: ABVD treatment is associated with a high frequency of actionable distress, with physical and emotional problems acting as primary drivers. Female patients may be particularly vulnerable, while cancer survivors may be uniquely resilient. These findings demonstrate the need to thoroughly screen for and appropriately tailor distress management strategies for HL patients during treatment with ABVD. [ABSTRACT FROM AUTHOR]

Background A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates. Objectives We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic. Methods We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups. Results Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5–71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0–16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30–1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%. Conclusions These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone. [ABSTRACT FROM AUTHOR]

Purpose: Hodgkin lymphoma (HL) survivors face long-term, elevated risk of treatment-related sequelae, including psychosocial distress associated with poor health outcomes. The magnitude and sources of distress are not well described in the routine care of HL outside of clinical trials.Methods: We conducted a retrospective cohort study of patients visiting a tertiary-care center for treatment or long-term follow-up of HL. Patient-reported distress was documented using the National Comprehensive Cancer Network Distress Thermometer (DT) and Problem List. Three survivor groups were compared using descriptive methods: on treatment, surviving < 5 years, and surviving ≥ 5 years since diagnosis.Results: A total of 1524 DT were abstracted for 304 patients (106 on treatment, 77 surviving < 5 years, and 121 surviving ≥ 5 years). Distress was low overall (median DT = 1, inter-quartile range 0-4) and was similar across survivor groups. However, actionable distress (score ≥ 4) was reported at 29.5% of clinical encounters. Patients on treatment more frequently reported actionable distress (32.5% of visits) compared with patients surviving < 5 years (20.4%) and ≥ 5 years (28.7%) (P = 0.065). Distress was associated primarily with physical and emotional problems, especially fatigue, worry, and sleep. We did not observe any associations between distress and clinical prognostic factors.Conclusions: Distress burden is low in HL, but survivorship is marked by periods of actionable distress, largely related to physical symptoms and emotional issues. This burden may be higher when on treatment and is unrelated to disease-related prognostic factors. Survivorship research typically focuses on the post-therapy period, but our results support testing the efficacy of interventions to address distress in HL during active treatment as well. [ABSTRACT FROM AUTHOR]

Introduction Previous research shows immune response to vaccination differs by sex but this has not been explored for IMVAMUNE ® , a replication-deficient smallpox vaccine developed in response to the potential for bioterrorism using smallpox. Methods We conducted a participant-level meta-analysis ( N = 275, 136 men, 139 women) of 3 randomized trials of IMVAMUNE conducted at 13 centers in the US through a federally-funded extramural research program. Studies were eligible for inclusion if they tested the standard dose (1 × 10 8 TCID 50 /mL on Days 0 and 28) of liquid formulation IMVAMUNE, were completed at the time of our search, and enrolled healthy vaccinia -naïve participants. Models of the peak log 2 ELISA and PRNT titers post-second vaccination were constructed for each study with sex as a covariate. Results from these models were combined into random effects meta-analyses of the sex difference in response to IMVAMUNE. We then compared this approach with fixed effects models using the combined participant level data. Results In each study the mean peak log 2 ELISA titer was higher in men than women but no single study demonstrated a statistically significant difference. Combination of the adjusted study-specific estimates into the random effects model showed a higher mean peak log 2 -titer in men compared with women (absolute difference [men–women]: 0.32, 95% CI: 0.02–0.60). Fixed effects models controlling for study showed a similar result (log 2 ELISA titer, men–women: 0.34, 95% CI: 0.04–0.63). This equates to a geometric mean peak titer that is approximately 27% higher in men than women (95% CI: 3–55%). Peak log 2 PRNT titers were also higher (although not significantly) in men (men–women: 0.14, 95% CI: −0.30 to 0.58). Conclusion Our results show statistically significant differences in response to IMVAMUNE comparing healthy, vaccinia-naïve men with women and suggest that sex should be considered in further development and deployment of IMVAMUNE and other MVA-based vaccines. [ABSTRACT FROM AUTHOR]

Introduction: Passive smoke is carcinogenic but its association with head and neck squamous cell carcinoma (HNSCC) is uncertain. Methods: We conducted a case-control study of childhood passive smoke exposure (CPSE) and HNSCC in 858 cases and 806 frequency-matched controls using an interviewer-administered questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression controlling for adult smoking in the total study population, and in never-smokers only (184 cases and 415 controls). CPSE was also studied in oropharyngeal separately from other HNSCC using polytomous logistic regression. Results: CPSE was associated with HNSCC (OR, 1.28; 95% CI, 1.01-1.63) after controlling for adult smoking and other factors. This association was similar in magnitude, although not statistically significant, among subjects who never smoked as adults (OR, 1.19, 95% CI, 0.80-1.76). CPSE was associated more strongly with oropharyngeal cancer (a HNSCC subtype commonly associated with human papillomavirus (HPV) infection) than with HNSCC at nonoropharyngeal sites (OR, 2.02; 95% CI, 1.01-4.06, N = 52 cases vs. OR, 1.04; 95% CI, 0.68-1.60, N = 132 cases; P-for-heterogeneity = 0.08). Conclusions: Data from this large US-based case control study suggest a role for CPSE in HNSCC etiology. [ABSTRACT FROM AUTHOR]

Introduction: Functional polymorphisms in drug metabolizing enzymes (DMEs) may be determinants of survival in oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods: OOSCC cases (N = 159) with a history of either tobacco or alcohol use were genotyped for polymorphisms in eight DMEs. Overall and disease-specific survival were analyzed using Kaplan-Meier plots and the log-rank test. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) in exploratory analyses of patient subgroups. Results: Kaplan-Meier analyses showed Nacteyltransferase- 2 (NAT2) fast acetylators experienced a 19.7% higher 5-year survival rate than slow acetylators (P = 0.03) and this association was similar in oropharyngeal and oral cancer. After multiple adjustment, including tumor site and stage, the NAT2 fast acetylator phenotype was associated with improved overall survival (vs. slow acetylators) provided chemotherapy or radiation were not used (HR, 0.26; 95% CI, 0.10-0.66). However, NAT2 phenotype was unrelated to survival in patients treated with chemoradiotherapy (HR, 1.21; 95% CI, 0.54-2.73) or radiotherapy (HR, 0.67; 95% CI, 0.31-1.59) (P-for- NAT2/treatment-interaction = 0.04). Normal activity GSTP1 was associated with a 19.2% reduction in 5- year disease-specific survival relative to reduced activity GSTP1 (P = 0.04) but this association was not modified by treatment. Conclusions: Our results suggest that functional polymorphisms in NAT2 and GSTP1 are associated with OOSCC survival. Confirmation of these results in larger studies is required. [ABSTRACT FROM AUTHOR]

Prospective studies of lifestyle and non-Hodgkin lymphoma (NHL) are conflicting, and some are inconsistent with case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was used to evaluate risk of NHL and its subtypes in association with anthropometric factors, smoking, and alcohol consumption in a prospective cohort study. Lifestyle was assessed via questionnaire among 142,982 male and female participants aged 55–74 years enrolled in the PLCO Trial during 1993–2001. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards regression. During 1,201,074 person-years of follow-up through 2006, 1,264 histologically confirmed NHL cases were identified. Higher body mass index (BMI; weight (kg)/height (m)2) at ages 20 and 50 years and at baseline was associated with increased NHL risk (Ptrend < 0.01 for all; e.g., for baseline BMI ≥30 vs. 18.5–24.9, hazard ratio = 1.32, 95% confidence interval: 1.13, 1.54). Smoking was not associated with NHL overall but was inversely associated with follicular lymphoma (ever smoking vs. never: hazard ratio = 0.62, 95% confidence interval: 0.45, 0.85). Alcohol consumption was unrelated to NHL (drinks/week: Ptrend = 0.187). These data support previous studies suggesting that BMI is positively associated with NHL, show an inverse association between smoking and follicular lymphoma (perhaps due to residual confounding), and do not support a causal association between alcohol and NHL. [ABSTRACT FROM PUBLISHER]

• Machine learning (ML) predicted improvement in a community behavioral health treatment program. • Unique client profiles were identified for children with and without autism spectrum disorder. • Child and Adolescent Needs and Strengths (CANS) decision support initiatives can improve using ML. The CANS is the most popular measurement tool in the System of Care (SoC), with the potential to generate an estimated 1.9 million evaluations per year in the United States. This dataset has broad potential for decision support and outcomes monitoring, yet many SoC services do not yet leverage this information asset. We report here the results of a pilot project in which we applied machine learning methods to CANS data for the purpose of identifying clinical profiles associated with improvement in a public community-based behavioral health program in Pennsylvania. We analyzed over 7,000 CANS from 3,385 children who participated in Pennsylvania's Medicaid-funded behavioral health rehabilitation services (BHRS) program during 2013–2019. A gradient boosting classifier was developed to identify children most likely to experience a total score improvement on the CANS while participating in BHRS. Separate models were constructed for children with and without autism spectrum disorder (ASD). CANS-based clinical profiles associated with improvement were also identified. Analyses were run using Python Sci-Ki version 0.20.3 and Linearly Interpretable Model-agnostic Explanations (LIME) version 0.1.1.33. The mean age of BHRS participants was 9.85 years (standard deviation: 3.47) and the majority were white (54%) or African American (11.5%). The median length of stay was 963 days (range: 541–2,008) and 39% (N = 1,330) had a diagnosis of ASD. A total of 49.9% of children had a CANS total score improvement. Precision of the gradient boosting classifier was 70% and 79% for children with and without ASD, respectively. Fourteen profiles were associated with improvement in ASD (mean probability of improvement per profile = 0.95, range: 0.88–1.0) and 55 such profiles were identified in children without ASD (mean probability of improvement: 0.91, range: 0.86–1.0). Machine learning can be applied to the CANS to identify children who have high probability of improvement in BHRS. These methods may have utility as an adjunct to existing decision support systems for SoC services. [ABSTRACT FROM AUTHOR]

More than 25 million Americans have limited English proficiency (LEP) and are more likely than English-proficient (EP) patients to have poor health literacy, not understand their diagnosis, or experience complications from adverse drug effects. Hematopoietic stem cell transplantation (HSCT) is a potentially curative procedure for a variety of malignant and non-malignant diseases. However, HSCT requires prolonged hospitalization and excellent medication adherence to achieve good outcomes. Communication barriers between providers and LEP families of pediatric HSCT patients may further complicate this process and negatively affect clinical outcomes. The objectives of this study were to compare HSCT outcomes of Hispanic pediatric patients with LEP and EP families. Outcomes included overall survival, relapse, length of hospitalization, frequency of re-hospitalization and post-transplant complications including infections and graft-versus-host disease (GVHD). We hypothesized that LEP would be associated with worse outcomes. We conducted a retrospective review of Hispanic or Latino pediatric patients receiving HSCT at Duke University from January 1, 2000 through March 15, 2019. Patients and families were identified as LEP or EP based on clinicians' notes, social work documentation or the signature of a Spanish interpreter on treatment consents. A total of 84 Hispanic/Latino patients were identified with 53 (63.1%) having LEP. There were no significant differences in age at transplant, sex, and race between these groups. Donor types, graft sources, and diagnoses were similar with the exception of more genetic diagnoses in the EP group (32%) than LEP (13%). The cumulative incidence of relapse, neutrophil engraftment, and acute GVHD were similar in both groups, as were the frequency of post-transplant infection and readmission. LEP patients were hospitalized on average 13 days longer than EP patients (Figure 1, p=0.06) and were more likely to have pre-transplant CMV reactivity (66%) than EP patients (30%, Figure 2, p=0.001). Overall survival was lower in LEP than EP but was not statistically significant (Figure 3). Multivariable Cox modeling suggested a potentially higher risk of death in LEP vs EP (hazard ratio=1.56, 95% CI: 0.38, 6.23). Spanish-speaking patients with LEP undergoing HSCT may be at risk for prolonged hospitalization and are more likely to have pre-transplant CMV reactivity. These factors are known to be associated with post-transplant complications and death. Our results suggest LEP families are at higher risk for poor HSCT outcomes. Further study is warranted in a larger cohort. [ABSTRACT FROM AUTHOR]

With increased access to biomedical and electronic health records data and the complexity of research questions, individuals in residency programmes who aim to conduct research require specialized educational programmes and biostatistics support. Biostatistics collaboration units in academic health centres often work with residents to conduct data‐intensive research. These units face numerous challenges related to providing training in statistical literacy and collaborating on resident‐led research within very restricted timelines. Since 2019, the Duke Biostatistics, Epidemiology, and Research Design (BERD) Methods Core has supported over 247 resident‐led projects by developing tools and resources to address these challenges. This manuscript presents novel processes and training materials that other institutions can use to help biostatistics collaboration units effectively support resident training programmes. We provide a framework to support the development of collaborative teams, along with specialized training materials for residents who collaborate with these teams. [ABSTRACT FROM AUTHOR]

Collaborative quantitative scientists, including biostatisticians, epidemiologists, bioinformaticists, and data‐related professionals, play vital roles in research, from study design to data analysis and dissemination. It is imperative that academic health care centers (AHCs) establish an environment that provides opportunities for the quantitative scientists who are hired as staff to develop and advance their careers. With the rapid growth of clinical and translational research, AHCs are charged with establishing organizational methods, training tools, best practices, and guidelines to accelerate and support hiring, training, and retaining this staff workforce. This paper describes three essential elements for building and maintaining a successful unit of collaborative staff quantitative scientists in academic health care centers: (1) organizational infrastructure and management, (2) recruitment, and (3) career development and retention. Specific strategies are provided as examples of how AHCs can excel in these areas. [ABSTRACT FROM AUTHOR]

Palliative Care (PC) is poorly understood by laypersons. However, little is known about what ambulatory patients with cancer understand about PC or what barriers to access exist. Outpatients undergoing cancer treatment completed a survey evaluating their familiarity and knowledge of PC, Palliative Care Knowledge Scale (PaCKS), feelings towards PC (before and after reading a definition of PC), barriers to PC, and prognostic understanding. We summarized responses descriptively and used logistic regression models to examine variables associated with familiarity and interest. The survey response rate was 32%. Of 151 participants, 58.9% reported familiarity with PC. The average PaCKs score was 11.9 out of 13 (standard deviation, 1.4), with 46.4% receiving a perfect score, indicating high knowledge of PC. Patients diagnosed more than one year ago had significantly increased odds of being familiar with PC (OR 2.93; 95% CI 1.37–6.25). More participants reported future interest in PC compared to current interest (74.2% vs 44.4%, respectively). Patients with stage III or IV cancer had significantly increased odds of having a current interest in receiving PC compared to patients with stage I or II disease (OR 2.66; 95% CI: 1.05, 6.76). Participants reported feeling significantly less anxious and more reassured after reading a standardized definition of PC (P < 0.05). Outpatients with cancer who are being treated at a large academic cancer center exhibit high awareness and knowledge of PC, but anxiety toward PC persists. Factors beyond knowledge may perpetuate the delayed or lack of involvement with PC. In this cross-sectional study of outpatients with cancer, findings suggest that high knowledge of PC may co-exist with a lingering uneasiness towards the service. Additionally, factors beyond knowledge, such as logistic barriers, anxiety, and oncologists' preference may be perpetuating the delay or lack of involvement in PC. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success. Unrelated umbilical cord blood transplantation (UCBT) provides a readily available alternative donor source for patients lacking matched related donors. Accordingly, we report the results of UCBT in 14 children treated between 1998 and 2016. All children received standard HLH chemotherapy before UCBT. The median age at diagnosis was 2.7 months (range, .8 to 10.4) and at transplantation was 7.5 months (range, 3.8 to 17). Ten patients received MAC with busulfan/cyclophosphamide/etoposide /antithymocyte globulin (ATG) (n = 5), busulfan/cyclophosphamide /ATG (n = 4), or busulfan /melphalan/ATG (n = 1). Four patients received reduced-toxicity conditioning (RTC) with alemtuzumab/fludarabine/melphalan/hydroxyurea ± thiotepa. Cord blood units were mismatched at either 1 (n = 9) or 2 (n = 5) loci and delivered a median total nucleated cell dose of 11.9 × 10 7 /kg (range, 4.6 to 27.9) and CD34 + dose of 3.1 × 10 5 /kg (range, 1.1 to 6.8). The cumulative incidence of neutrophil engraftment by day 42 was 78.6% (95% confidence interval [CI], 42.9% to 93.4%) with a median of 19 days (range, 13 to 27), and that for platelet (50,000) engraftment by day 100 was 64.3% (95% CI, 28.2% to 85.7%) with a median of 51 days (range, 31 to 94). Six patients developed either grade II (n = 5) or grade IV (n = 1) acute graft-versus-host disease (GVHD); no extensive chronic GVHD was seen. Ten patients (71.4%) are alive and well at a median of 11.2 years after transplantation (range, .85 to 18.25), 9 of whom maintain sustained full donor chimerism after a single UCBT, whereas 1 patient with autologous recovery after first UCBT with RTC has achieved full donor chimerism after a second UCBT with MAC. This series demonstrates that, in combination with standard HLH therapy, UCBT after MAC or RTC conditioning can provide long-term survival with durable complete donor chimerism comparable to that of conventional donors. UCBT should be considered for patients with HLH lacking a fully matched related or unrelated adult donor. [ABSTRACT FROM AUTHOR]

• We describe the mNSCLC patient experience with immunotherapy vs chemotherapies. • Distress was worst before treatment start and decreased over time. • Patients receiving immunotherapy had lower rates of unplanned healthcare encounters. • One-third of all patients were seen by palliative care. • There are potential unmet supportive care needs in the mNSCLC/IO treatment era. There are limited real-world data about patient-reported outcomes with immunotherapies (IO) in metastatic non-small cell lung cancer (mNSCLC). We describe patient-reported distress and clinical outcomes with IO-based treatments or cytotoxic chemotherapies (Chemo). We conducted a single-institution retrospective chart review of adults with mNSCLC treated at Duke from 03/2015 to 06/2020. At each visit, patients self-reported their distress level and sources of distress using the NCCN Distress Thermometer (DT) and its 39-item Problem List. We abstracted demographic, clinical, distress, and investigator assessed-clinical response data, then analyzed these using descriptive statistics and generalized estimating equations. Data from 152 patients were analyzed in four groups: Chemo alone, IO + Chemo, single agent IO, dual agent IO. Distress was worse before treatment start in all groups, and the odds of actionable distress (DT score > 4) decreased by 10 % per month. The most frequent sources of distress were physical symptoms (e.g., fatigue, pain), which remained high longitudinally. Patients receiving IO had higher clinical response rates and a lower rate of unplanned healthcare encounters compared to patients treated with Chemo alone. Only one-third of all patients were seen by palliative care. This single-center, real-world evidence study demonstrates that patients with mNSCLC experience significant distress prior to starting first-line treatment. IO treatment was associated with higher clinical benefit rates and lower healthcare utilization compared to chemotherapy. Symptom distress persists over time, highlighting potential unmet palliative and supportive care needs in mNSCLC care in the IO treatment era. [ABSTRACT FROM AUTHOR]

This manuscript describes an experiential learning programme for future collaborative biostatisticians (CBs) developed within an academic medical centre. The programme is a collaborative effort between the Biostatistics, Epidemiology, and Research Design (BERD) Methods Core and the Master of Biostatistics (MB) programme, both housed in the Department of Biostatistics and Bioinformatics at Duke University School of Medicine and supported in partnership with the Duke Clinical and Translational Science Institute. To date, the BERD Core Training and Internship Program (BCTIP) has formally trained over 80 students to work on collaborative teams that are integrated throughout the Duke School of Medicine. This manuscript focuses on the setting for the training programme, the experiential learning model on which it is based, the structure of the programme, and lessons learned to date. [ABSTRACT FROM AUTHOR]

Background: Inflammatory responses from benign conditions can cause non‐cancer‐related elevations in tumor markers. The severe acute respiratory coronavirus 2 (SARS‐CoV‐2) induces a distinct viral inflammatory response, resulting in coronavirus disease 2019 (COVID‐19). Clinical data suggest carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA 19–9), and cancer antigen 125 (CA 125) levels might rise in patients with COVID‐19. However, available data excludes cancer patients, so little is known about the effect of COVID‐19 on tumor markers among cancer patients. Methods: We conducted a case series and identified patients with a positive SARS‐CoV‐2 PCR test, diagnosis of a solid tumor malignancy, and a CEA, CA 19–9, CA 125, or CA 27–29 laboratory test. Cancer patients with documented COVID‐19 infection and at least one pre‐ and two post‐infection tumor marker measurements were included. We abstracted the electronic health record for demographics, cancer diagnosis, treatment, evidence of cancer progression, date and severity of COVID‐19 infection, and tumor marker values. Results: Seven patients were identified with a temporary elevation of tumor marker values during the post‐COVID‐19 period. Elevation in tumor marker occurred within 56 days of COVID‐19 infection for all patients. Tumor markers subsequently decreased at the second time point in the post‐infectious period among all patients. Conclusion: We report temporary elevations of cancer tumor markers in the period surrounding COVID‐19 infection. To our knowledge this is the first report of this phenomenon in cancer patients and has implications for clinical management and future research. [ABSTRACT FROM AUTHOR]

Banked, unrelated umbilical cord blood provides access to hematopoietic stem cell transplantation for patients lacking matched bone marrow donors, yet 10% to 15% of patients experience graft failure or delayed engraftment. This may be due, at least in part, to inadequate potency of the selected cord blood unit (CBU). CBU potency is typically assessed before cryopreservation, neglecting changes in potency occurring during freezing and thawing. Colony-forming units (CFUs) have been previously shown to predict CBU potency, defined as the ability to engraft in patients by day 42 posttransplant. However, the CFU assay is difficult to standardize and requires 2 weeks to perform. Consequently, we developed a rapid multiparameter flow cytometric CBU potency assay that enumerates cells expressing high levels of the enzyme aldehyde dehydrogenase (ALDH bright [ALDHbr]), along with viable CD45+ or CD34+ cell content. These measurements are made on a segment that was attached to a cryopreserved CBU. We validated the assay with prespecified criteria testing accuracy, specificity, repeatability, intermediate precision, and linearity. We then prospectively examined the correlations among ALDHbr, CD34+, and CFU content of 3908 segments over a 5-year period. ALDHbr (r = 0.78; 95% confidence interval [CI], 0.76-0.79), but not CD34+ (r = 0.25; 95% CI, 0.22-0.28), was strongly correlated with CFU content as well as ALDHbr content of the CBU. These results suggest that the ALDHbr segment assay (based on unit characteristics measured before release) is a reliable assessment of potency that allows rapid selection and release of CBUs from the cord blood bank to the transplant center for transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Cancer patients' sources of distress are often unaddressed, and patient-reported distress data could be utilized to identify those with unmet and impending care needs. We explored the association between moderate/severe distress and healthcare utilization in a large sample of non-small cell lung cancer (NSCLC) and non-colorectal gastrointestinal cancer patients. Methods and materials: Adult patients treated between July 2013 and March 2019. Data from the NCCN Distress Thermometer (DT) and the accompanying "Problem List" were extracted from the EHR. A DT score of ≥ 4 indicates "actionable distress." Statistical analysis was performed using descriptive analysis for patient characteristics, clinical outcomes, and sources of distress. Generalized linear mixed models were fit to determine the relationship between distress and healthcare utilization (hospitalization, emergency department (ED) visit, or both). Results: The ten most frequently reported problems were from the Physical and Emotional domains of the Problem List. Distress was mostly related to physical symptoms (pain, fatigue) and emotional issues (worry, fears, sadness, nervousness). Patients with actionable distress generally reported more problems across all their visits. Actionable distress was associated with higher odds of the composite outcome measure of hospitalization or visiting the ED, within both the next 3 months (OR = 1.37; 95% CI = 1.19, 1.58; p < 0.001) and 6 months (OR = 1.19; 95% CI = 1.03, 1.37; p = 0.019). Conclusion: Patients with significant distress had marked utilization of ED and inpatient services. DT scores are a source of untapped data in the EHR that can highlight patients in need of intervention, including palliative care and cancer support services. [ABSTRACT FROM AUTHOR]

Purpose: Adults with acute myeloid leukemia (AML) face considerable distress and often have a poor prognosis. However, little is known about these patients' perceptions of prognosis and how this relates to emotional well-being (EWB). Methods: We conducted a prospective, observational study of 50 adult patients with AML initiating chemotherapy, and surveyed them longitudinally for 6 months about their prognosis, treatment goals, quality of life, and EWB (by FACT-G). We derived a prognostic estimate for each patient based on data from published trials summarized in National Comprehensive Care Network Guidelines. We used descriptive statistics and longitudinal modeling to test the hypothesis that more accurate prognostic awareness is associated with worse EWB. Results: Most patients (n = 43; 86%) had an objectively poor prognosis attributable to relapsed disease, complex karyotype, or FLT3 mutation. Yet, 74% of patients reported expecting a 50% or greater chance of cure. Patients with a poor prognosis more often had discordant prognostic estimates, compared to those with favorable risk AML (OR = 7.25, 95% CI 1.21, 43.37). Patient-reported prognostic estimates did not vary significantly over time. At baseline, patients who better understood their prognosis had worse EWB and overall quality-of-life scores (EWB 12 vs. 19.5; p = 0.01; FACT-G 65 vs. 75.5; p = 0.01). Conclusion: Patients with AML overestimate their prognosis, and awareness of a poor prognosis is associated with worse emotional well-being. Efforts are needed to improve patients' understanding of their prognosis, and to provide more psychosocial support and attention to well-being as part of high-quality leukemia care. [ABSTRACT FROM AUTHOR]

Purpose: Acute myeloid leukemia (AML) is a hematologic malignancy characterized by a poor prognosis but also a paradoxical possibility of cure. This renders decision-making complex and imminent. Unfortunately, many patients with AML misestimate their prognosis and treatment risk. While decision aids can improve illness understanding and reduce decisional conflict, there are no validated decision aids for AML. We developed and tested a novel AML decision aid (NCT03442452).Methods: Patients (n = 20) were recruited at Duke University from May 2018 to February 2019. Participants completed assessments of AML knowledge and decisional conflict, before and after using the electronic decision aid. The primary endpoint was feasibility (endpoint met if > 80% of study participants completed all study components). Secondary analyses of efficacy were conducted using paired t tests for dependent pre-/post-samples.Results: The primary endpoint of feasibility was met (100% of participants completed all study components). Secondary analyses showed improved knowledge and reduced decisional conflict after using the decision aid. Knowledge scores improved from a mean of 11.8 (out of 18) correct items at baseline to 15.1 correct items after using the decision aid (mean difference 3.35; p < 0.0001). Decisional conflict scores reduced significantly from baseline to post-test as well (mean difference - 6.5; p = 0.02).Conclusion: These findings suggest that our AML decision aid is a useful tool to improve the patient experience and promote shared decision-making in AML. A randomized efficacy trial is planned. [ABSTRACT FROM AUTHOR]

Purpose: Utilization of electronic patient-reported outcomes (ePROs) in the clinic can improve quality of life and prolong survival in cancer care. However, there remain unanswered questions regarding trends in missing data and the potential effect on real-time patient care. Methods: This study utilized a prospectively collected dataset of ePROs from oncology clinics that administered the Patient Care Monitor 2.0 (PCM), a validated symptoms survey assessing 78 items for men, and 86 for women. We tabulated the frequency of missing items, by item and domain (emotional, functional and physical symptom-related), and examined these by age, gender, education, race and marital status. Results: Within 20,986 encounters, there were responses to at least 1 PCM item from 6933 unique patients. The highest frequency of missing answers occurred for: "attend a paid job" (10.7%), "reduced sexual enjoyment" (3.8%), and "run" (3.7%). By domain, 12.3% of functional, 8.4% of physical symptom-related, and 1.6% of emotional constructs contained at least one missing item. For functional and physical symptom-related items, missingness was most common in patients >60 years old. Conclusion: The frequency of missingness was highest for functional items, like attending a paid job, suggesting that some respondents (e.g., retirees without a paid job) skipped questions that were less applicable to them. More universal issues for cancer patients, such as emotional well-being, had much lower frequencies of missingness. This suggests differential item completion that warrants further study to understand the inherent drivers. Identifying causes of missingness could improve the clinical utility of ePROs and highlight opportunities to personalize care. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS), a spectrum of heterogeneous hematopoietic stem cell diseases, vary in clinical severity, response to therapy, and propensity toward progression to acute myeloid leukemia. These are acquired clonal disorders resulting from somatic mutations within the hematopoietic stem or progenitor cell population. Understanding the natural history and the risk of developing leukemia and other adverse outcomes is dependent on access to well-annotated biospecimens linked to robust clinical and molecular data. To facilitate the acquisition and distribution of MDS biospecimens to the wider scientific community and support scientific discovery in this disease, the National MDS Natural History study was initiated by the National Heart, Lung, and Blood Institute (NHLBI) and is being conducted in collaboration with community hospitals and academic medical centers supported by the National Cancer Institute (NCI). The study will recruit up to 2000 MDS patients or overlapping myeloproliferative neoplasms (MDS/MPN) and up to 500 cases of idiopathic cytopenia of undetermined significance (ICUS). The National MDS Natural History Study (NCT02775383) will offer the world's largest disease-focused tissue biobank linked to longitudinal clinical and molecular data in MDS. Here, we report on the study design features and describe the vanguard phase of 200 cases. The study assembles a comprehensive clinical database, quality of life results, laboratory data, histopathology slides and images, genetic information, hematopoietic and germline tissues representing high-quality biospecimens and data from diverse centers across the United States. These resources will be available to the scientific community for investigator-initiated research. [ABSTRACT FROM AUTHOR]

Objective, quantitative measures of caregiver-child interaction during play are needed to complement caregiver or examiner ratings for clinical assessment and tracking intervention responses. In this exploratory study, we examined the feasibility of using automated video tracking, Noldus EthoVision XT, to measure 159 2-to-7-year-old autistic children’s patterns of movement during play-based, caregiver-child interactions and examined their associations with standard clinical measures and human observational coding of caregiver-child joint engagement. Results revealed that autistic children who exhibited higher durations and velocity of movement were, on average, younger, had lower cognitive abilities, greater autism-related features, spent less time attending to the caregiver, and showed lower levels of joint engagement. After adjusting for age and nonverbal cognitive abilities, we found that children who remained in close proximity to their caregiver were more likely to engage in joint engagement that required support from the caregiver. These findings suggest that video tracking offers promise as a scalable, quantitative, and relevant measure of autism-related behaviors. [ABSTRACT FROM AUTHOR]

Background: The cell dose infused for cord blood transplantation strongly correlates with outcomes following transplantation. Post thaw recoveries can be improved by washing cord blood units (CBUs) in dextran/albumin. Early methods used a labor-intensive manual process. We have recently developed and validated an automated washing method. We now report our results of a study comparing cellular recoveries achieved after manual and automated wash, as well as the impact on engraftment following allogeneic transplantation.Study Design and Methods: CBUs distributed by the Carolinas Cord Blood Bank for clinical use at Duke University after manual or automated wash were included in this report. Precryopreservation total nucleated cell count, total CD34+, colony-forming units, recoveries, and sterility were analyzed by wash method. Patient age, cell dose/weight, diagnosis, conditioning regimen, immunosuppression, and time to neutrophil engraftment were also analyzed.Results: Manual and automated washed CBUs yielded similar total nucleated cell count and total CD34+ recoveries. Significantly higher colony-forming units recoveries were achieved after automated washing. Patients who received CBUs washed via an automated method experienced earlier neutrophil engraftment.Conclusion: While manual and automated washing achieved similar post thaw cellular recoveries, automated washed CBUs demonstrated higher colony-forming unit recovery, which is an important predictor of potency and engraftment. Furthermore, we demonstrated that automated washing was associated with earlier neutrophil engraftment. Our findings favor the use of an automated wash method over a manual approach. [ABSTRACT FROM AUTHOR]

Nucleotide excision repair (NER) plays a critical role in the development of smoking-related cancers. We hypothesize that mRNA expression levels of NER genes are associated with risk of the squamous cell carcinoma of head and neck (SCCHN). To test this hypothesis, we conducted a case-control study of 260 SCCHN patients and 246 cancer-free controls by measuring the mRNA expression levels of eight core NER genes in cultured peripheral lymphocytes. Compared with the controls, cases had statistically signifcantly lower expression levels of DDB1 and ERCC3 (P = 0.015 and 0.041, respectively). Because DDB1 and ERCC3 expression levels were highly correlated, we used DDB1 for further multivariate analyses and modeling. After dividing the subjects by controls' quartiles of expression levels, we found an association between an increased risk of SCCHN and low DDB1 expression levels [adjusted ORs and 95% CIs: 1.92 and 1.11-3.32, 1.48 and 0.85-2.59, 2.00 and 1.15-3.45 for the 2nd-4th quartiles, respectively, compared with the 1st quartile; Ptrend = 0.026]. We also identified a multiplicative interaction between sex and DDB1 expression levels (P = 0.007). Finally, the expanded model with gene expression levels, in addition to demographic and clinical variables, on SCCHN risk was significantly improved, especially among men. In conclusion, reduced DDB1 expression levels were associated with an increased risk of SCCHN. However, these results need to be validated in larger studies. [ABSTRACT FROM AUTHOR]

1. Describe deficiencies in the educational quality of YouTube videos and recommendations for improvement 2. Assemble a toolkit of strategies to increase YouTube video search rank and viewer engagement Insufficient knowledge and misconceptions about hospice philosophy engender hospice underutilization. Given its increasing use for health-related queries, YouTube may be an information source for hospice patients and caregivers. We examined hospice videos on YouTube for their hospice relevance, information coverage, quality, understandability, and character representations. We used the YouTube Data API to search YouTube for the top 100 videos with the keyword "hospice" under the "relevance" search setting. After examining all videos, we excluded videos that were irrelevant, >6 min, non-English, or duplicative. Using a multireviewer consensus technique, we assessed whether videos addressed features and misconceptions about hospice, their quality, and their understandability via the mDISCERN and PEMAT-A/V tools, respectively, and attributes of depicted characters. Among 100 videos, 4 irrelevant videos (2 among the top 20 search results) made up nearly one-third of all views and had more views, likes, dislikes, and comments than hospice-relevant videos (p < 0.01). Among included videos (n = 50), many failed to address fundamental information about hospice, including its eligibility criteria (86.0%) and services (60.0%). Only 12.0% of videos mentioned that hospice does not imply "giving up" and 6.0% that hospice is not for only the final days of life. Most videos (64.0%) had high quality but rarely provided additional resources for viewers. Additionally, 62.0% of videos had high understandability, albeit with organizational deficiencies. Racial and ethnic minorities were poorly represented (89.3% Caucasian). Chaplains, social workers, therapists, and volunteers were each depicted in, at most, 4.0% of videos. YouTube has limitations in its usefulness as an information source for hospice patients and caregivers. Our study identifies a need for hospice and palliative care organizations to improve their presence on YouTube by better leveraging the YouTube search algorithm and addressing information silos and viewer engagement gaps. [ABSTRACT FROM AUTHOR]

DUOC-01 is a cord-blood derived, macrophage-based cell therapy product, developed by our group to treat demyelinating conditions of the central nervous system. Recently, we demonstrated that DUOC-01 accelerated remyelination, decreased gliosis, and reduced cellular infiltration in the corpus callosum of immune-incompetent mice treated with cuprizone. To explore the mechanism and investigate whether DUOC-01 will be effective in other experimental models of demyelination, we tested DUOC-01 in lysophosphatidylcholine (LPC) mediated demyelinated murine organotypic cerebellar brain slices and a mouse model of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. In the cerebellar brain slices, we found that DUOC-01 enhanced remyelination, reduced gliosis, and promoted the proliferation of oligodendrocyte progenitor cells in brain slices demyelinated by LPC compared to the untreated control samples. When we injected DUOC-01 cells into the cerebrospinal fluid of mice immunized for EAE, we found decreased severity of clinical disease compared to the vehicle injected control. Currently we are analyzing single cell sequencing data to determine various populations present in DUOC-01 cultures and to understand the functional pathways responsible for promoting remyelination and reducing neuroinflammation. Overall, our data suggest that DUOC-01 could be beneficial in treating diverse neurological conditions with demyelination. [ABSTRACT FROM AUTHOR]