Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study.

OBJECTIVE: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not. DESIGN: Secondary analysis of multicenter retrospective cohort study. SETTING: Ten PICUs in the United States between 2009 and 2021. PATIENTS: Nine hundred thirteen patients 0-21 years old who died after WLST. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality). CONCLUSIONS: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

Admission Functional Status is Associated With Intensivists Perception of Extracorporeal Membrane Oxygenation Candidacy for Pediatric Acute Respiratory Failure.

OBJECTIVES: To determine the association between admission Functional Status Scale (FSS) category and perceived extracorporeal membrane oxygenation (ECMO) candidacy for pediatric acute respiratory failure. DESIGN: Prospective, cross-sectional study. SETTING: Single-center, quaternary, and ECMO referral academic children's hospital between March 2021 and January 2022. SUBJECTS: Pediatric intensivists directly caring for patients admitted with acute respiratory failure secondary to shock or respiratory disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pediatric intensivists were surveyed about current patients within 72 hours of initiation or escalation of invasive mechanical ventilation on whether they would offer ECMO should their patient deteriorate. Baseline functional status was assessed using trichotomized admission FSS: 1) normal/mild dysfunction (6-9), 2) moderate dysfunction (10-15), and 3) severe dysfunction (> 16). Multivariable logistic regression clustered by physician was used to assess the association between admission FSS category with perceived ECMO candidacy. Thirty-seven intensivists participated with 76% (137/180) of survey responses by those with less than 10 years of experience. 81% of patients (146/180) were perceived as ECMO candidates and 19% of patients (34/180) were noncandidates. Noncandidates had worse admission FSS scores than candidates (15.5 vs. 9, p < 0.001). After adjustment for age, admission FSS category of severe dysfunction had lower odds of perceived ECMO candidacy compared with normal to mild dysfunction (odds ratio [OR] 0.18 [95% CI, 0.06-0.56], p < 0.003). Patients with an abnormal communication subscore domain had the lowest odds of being considered a candidate (unadjusted OR 0.44 [95% CI, 0.29-0.68], p < 0.0001). CONCLUSIONS: In this prospective, single-center, cross-sectional study, admission FSS category indicating worse baseline functional status impacted pediatric intensivists' perceptions of ECMO candidacy for patients with acute respiratory failure. Abnormal FSS subscores in the neurocognitive domains were the most important considerations. Future studies should better seek to define the decision-making priorities of both parents and medical specialists for the utilization of ECMO in children with acute respiratory failure.

The Longitudinal Implementation Strategy Tracking System (LISTS): feasibility, usability, and pilot testing of a novel method.

BACKGROUND: Systematic approaches are needed to accurately characterize the dynamic use of implementation strategies and how they change over time. We describe the development and preliminary evaluation of the Longitudinal Implementation Strategy Tracking System (LISTS), a novel methodology to document and characterize implementation strategies use over time. METHODS: The development and initial evaluation of the LISTS method was conducted within the Improving the Management of SymPtoms during And following Cancer Treatment (IMPACT) Research Consortium (supported by funding provided through the NCI Cancer MoonshotSM). The IMPACT Consortium includes a coordinating center and three hybrid effectiveness-implementation studies testing routine symptom surveillance and integration of symptom management interventions in ambulatory oncology care settings. LISTS was created to increase the precision and reliability of dynamic changes in implementation strategy use over time. It includes three components: (1) a strategy assessment, (2) a data capture platform, and (3) a User's Guide. An iterative process between implementation researchers and practitioners was used to develop, pilot test, and refine the LISTS method prior to evaluating its use in three stepped-wedge trials within the IMPACT Consortium. The LISTS method was used with research and practice teams for approximately 12 months and subsequently we evaluated its feasibility, acceptability, and usability using established instruments and novel questions developed specifically for this study. RESULTS: Initial evaluation of LISTS indicates that it is a feasible and acceptable method, with content validity, for characterizing and tracking the use of implementation strategies over time. Users of LISTS highlighted several opportunities for improving the method for use in future and more diverse implementation studies. CONCLUSIONS: The LISTS method was developed collaboratively between researchers and practitioners to fill a research gap in systematically tracking implementation strategy use and modifications in research studies and other implementation efforts. Preliminary feedback from LISTS users indicate it is feasible and usable. Potential future developments include additional features, fewer data elements, and interoperability with alternative data entry platforms. LISTS offers a systematic method that encourages the use of common data elements to support data analysis across sites and synthesis across studies. Future research is needed to further adapt, refine, and evaluate the LISTS method in studies with employ diverse study designs and address varying delivery settings, health conditions, and intervention types.

National Cancer Institute funding for rapid cycle interventional research in cancer care delivery.

BACKGROUND: Rapid cycle interventional research can accelerate improvements to cancer care delivery and patient health outcomes by answering multiple questions as part of a single research study. To complement ongoing efforts to increase awareness of and support for rapid cycle interventional research, we conducted a systematic portfolio analysis of research grants funded by the National Cancer Institute on the topic. METHODS: We used standard portfolio analytic methods for identifying, coding, and synthesizing rapid cycle interventional research funded by the National Cancer Institute between 2016 and 2022. A codebook was used to standardize assessment of the grants by common study characteristics, intervention topics, and cancer care delivery context. RESULTS: We identified 26 grants, mostly funded since 2019, as rapid cycle interventional research. Most studies included adult or older adult target populations, used electronic systems for intervention delivery, and focused primarily on testing different components of interventions. Studies also used a range of study designs, intervention content areas, cancer sites, and across the cancer control continuum. CONCLUSIONS: The current portfolio analysis of funded rapid cycle interventional research grants suggests a growing albeit relatively small number of studies in this area. Several efforts are needed to continue to grow this area of research, including training programs, funding opportunities, and strengthening research-practice partnerships. This analysis provides a snapshot of current studies and highlights the opportunity for growing this important area of research to optimize cancer care delivery and improve patient outcomes.

Characteristics of patient navigation programs in the Cancer Moonshot ACCSIS colorectal cancer screening initiative.

BACKGROUND: Although patient navigation has shown promise for increasing participation in colorectal cancer screening and follow-up, little evidence is available to guide implementation of patient navigation in clinical practice. We characterize 8 patient navigation programs being implemented as part of multi-component interventions of the National Cancer Institute's Cancer Moonshot Accelerating Colorectal Cancer Screening and Follow-Up Through Implementation Science (ACCSIS) initiative. METHODS: We developed a data collection template organized by ACCSIS framework domains. The template was populated by a representative from each of the 8 ACCSIS research projects. We report standardized descriptions of 1) the socio-ecological context in which the navigation program was being conducted, 2) navigation program characteristics, 3) activities undertaken to facilitate program implementation (eg, training), and 4) outcomes used in program evaluation. RESULTS: ACCSIS patient navigation programs varied broadly in their socio-ecological context and settings, the populations they served, and how they were implemented in practice. Six research projects adapted and implemented evidence-based patient navigation programs; the remaining projects developed new programs. Five projects began navigation when patients were due for initial colorectal cancer screening; 3 projects began navigation later in the screening process, when patients were due for follow-up colonoscopy after an abnormal stool-test result. Seven projects relied on existing clinical staff to deliver the navigation; 1 hired a centralized research navigator. All project researchers plan to evaluate the effectiveness and implementation of their programs. CONCLUSIONS: Our detailed program descriptions may facilitate cross-project comparisons and guide future implementation and evaluation of patient navigation programs in clinical practice.

Advancing rapid cycle research in cancer care delivery: a National Cancer Institute workshop report.

Generating actionable research findings quickly and efficiently is critical for improving the delivery of cancer-related care and outcomes. To address this issue, the National Cancer Institute convened subject matter experts, researchers, clinicians, and patients for a 2-day virtual meeting in February 2022. The purpose of this meeting was to identify how rapid cycle interventional research methods can be used to generate findings useful in improving routine clinical practice. The meeting yielded an initial conceptualization of rapid cycle interventional research as being comprised of 6 key elements: use of iterative study designs; reliance on proximal primary outcomes; early and continued engagement with community and clinical partners; use of existing data sources to measure primary outcomes; facilitative features of the study setting and context; and consideration of appropriate rigor relative to intended use of findings. The meeting also identified the types of study designs that can be leveraged to conduct rapid cycle interventional research and provided examples of these; considered this approach from the perspective of key partners; described the clinical and data infrastructure, research resources, and key collaborations needed to support this work; identified research topics best addressed using this approach; and considered needed methodological advances. The National Cancer Institute is committed to exploring opportunities to encourage further development and application of this research approach as a means for better promoting improvements in the delivery of cancer-related care.

Influence of Cost-Related Considerations on Clinical Trial Participation: Results from the 2020 Health Information National Trends Survey (HINTS).

BACKGROUND: People experiencing financial burden are underrepresented in clinical trials. OBJECTIVE: Describe the prevalence of cost-related considerations influential to trial participation and their associations with person-level characteristics. DESIGN: This cross-sectional study used and assessed how three cost-related considerations would influence the decision to participate in a hypothetical clinical trial. PARTICIPANTS: A total of 3682 US adult respondents to the Health Information National Trends Survey MAIN MEASURES: Survey-weighted multivariable logistic regression estimated associations between respondent characteristics and odds of reporting cost-related considerations as very influential to participation. KEY RESULTS: Among 3682 respondents, median age was 48 (IQR 33-61). Most were non-Hispanic White (60%), living comfortably or getting by on their income (74%), with ≥ 1 medical condition (61%). Over half (55%) of respondents reported at least one cost-related consideration as very influential to trial participation, including if usual care was not covered by insurance (reported by 42%), payment for participation (24%), or support for participation (24%). Respondents who were younger (18-34 vs. ≥ 75, adjusted odds ratio [aOR] 4.3, 95% CI 2.3-8.1), more educated (high school vs.

Organ Donation From Patients on Extracorporeal Membrane Oxygenation at the Time of Death.

To describe the clinical characteristics and organ donation rate of patients supported by extracorporeal membrane oxygenation (ECMO) at the time of death. DESIGN: Retrospective observational study. Pearson chi-square and Fisher exact tests were used in statistical analyses. SETTING: One hundred twenty-seven acute care hospitals in New Jersey, Pennsylvania, and Delaware. PATIENTS: Adult and pediatric patients who were on ECMO at the time of referral to a large organ procurement organization (OPO) between 2016 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nineteen thousand nine hundred thirty patients were referred to the OPO between November 2016 and September 2020, of which 5,034 were medically suitable potential donors. Of this cohort, 143 patients were supported on ECMO at the time of OPO referral and 141 were included in analyses (median age 47 yr, 60% male). Thirty-three percent (46/141, median age 48 yr, 52% male) donated organs, compared with 50% of non-ECMO patients (p ≤ 0.0005). ECMO and non-ECMO patients had organs recovered but not transplanted at similar rates (11% vs 10%, p = 0.8). There were no significant differences in sex (p = 0.16) or ethnicity (p = 0.50) between organ donor and nondonor groups. Fifty-one percent (21/41) of organ donors donated after circulatory death and 49% (20/41) after brain death. Patients declared dead by neurologic criteria were more likely to donate (51%) than those declared dead by circulatory criteria (21%, p < 0.001). Frequency of cardiac arrest prior to ECMO was similar between donors and nondonors (p = 0.68). Thirty-nine percent (16/41) of donors had an out-of-hospital cardiac arrest (OHCA) and 51% (21/41) were cannulated via extracorporeal cardiopulmonary resuscitation (ECPR). The most common reason patients were not donors was that family declined (57%). CONCLUSIONS: One-third of patients referred to the OPO on ECMO at the time of death donated organs. While donation occurred less frequently after ECMO, ECMO and non-ECMO patients had organs used rather than discarded at a similar rate. Patients successfully donated following OHCA and/or ECPR. Clinicians should not consider ECMO a barrier to organ donation.

A Taxonomy of Objections to Brain Death Determination.

Family objections to evaluating a patient for death by neurologic criteria, or "brain death," are challenging for the family and the medical team. In this article, we categorize brain death evaluation refusals into a taxonomy: informational objections, emotional objections, and principled objections. We offer suggested approaches for clinicians to respond to refusals on the basis of the category. The category of objection may also be important in considering when accommodation of refusals should be considered. The goal in all such situations is to promote compassionate, ethical, and equitable care for the patient and family.

It's a worm-eat-worm world: Consumption of parasite free-living stages protects hosts and benefits predators.

Predation on parasites is a common interaction with multiple, concurrent outcomes. Free-living stages of parasites can comprise a large portion of some predators' diets and may be important resources for population growth. Predation can also reduce the density of infectious agents in an ecosystem, with resultant decreases in infection rates. While predator-parasite interactions likely vary with parasite transmission strategy, few studies have examined how variation in transmission mode influences contact rates with predators and the associated changes in consumption risk. To understand how transmission mode mediates predator-parasite interactions, we examined associations between an oligochaete predator Chaetogaster limnaei that lives commensally on freshwater snails and nine trematode taxa that infect snails. Chaetogaster is hypothesized to consume active (i.e. mobile), free-living stages of trematodes that infect snails (miracidia), but not the passive infectious stages (eggs); it could thus differentially affect transmission and infection prevalence of parasites, including those with medical or veterinary importance. Alternatively, when infection does occur, Chaetogaster can consume and respond numerically to free-living trematode stages released from infected snails (cercariae). These two processes lead to contrasting predictions about whether Chaetogaster and trematode infection of snails correlate negatively ('protective predation') or positively ('predator augmentation'). Here, we tested how parasite transmission mode affected Chaetogaster-trematode relationships using data from 20,759 snails collected across 4 years from natural ponds in California. Based on generalized linear mixed modelling, snails with more Chaetogaster were less likely to be infected by trematodes that rely on active transmission. Conversely, infections by trematodes with passive infectious stages were positively associated with per-snail Chaetogaster abundance. Our results suggest that trematode transmission mode mediates the net outcome of predation on parasites. For trematodes with active infectious stages, predatory Chaetogaster limited the risk of snail infection and its subsequent pathology (i.e. castration). For taxa with passive infectious stages, no such protective effect was observed. Rather, infected snails were associated with higher Chaetogaster abundance, likely owing to the resource subsidy provided by cercariae. These findings highlight the ecological and epidemiological importance of predation on free-living stages while underscoring the influence of parasite life history in shaping such interactions.

Resilience of native amphibian communities following catastrophic drought: Evidence from a decade of regional-scale monitoring.

The increasing frequency and severity of drought may exacerbate ongoing global amphibian declines. However, interactions between drought and coincident stressors, coupled with high interannual variability in amphibian abundances, can mask the extent and underlying mechanisms of drought impacts. We synthesized a decade (2009 - 2019) of regional-scale amphibian monitoring data (2273 surveys, 233 ponds, and seven species) from across California's Bay Area and used dynamic occupancy modeling to estimate trends and drivers of species occupancy. An extreme drought during the study period resulted in substantial habitat loss, with 51% of ponds drying in the worst year of drought, compared to <20% in pre-drought years. Nearly every species exhibited reduced breeding activity during the drought, with the occupancy of some species (American bullfrogs and California newts) declining by >25%. Invasive fishes and bullfrogs were also associated with reduced amphibian occupancy, and these taxa were locally extirpated from numerous sites during drought, without subsequent recovery-suggesting that drought may present an opportunity to remove invaders. Despite a historic, multi-year drought, native amphibians rebounded quickly to pre-drought occupancy levels, demonstrating evidence of resilience. Permanent waterbodies supported higher persistence of native species during drought years than did temporary waterbodies, and we therefore highlight the value of hydroperiod diversity in promoting amphibian stability.

A scoping review of de-implementation frameworks and models.

BACKGROUND: Reduction or elimination of inappropriate, ineffective, or potentially harmful healthcare services and public health programs can help to ensure limited resources are used effectively. Frameworks and models (FM) are valuable tools in conceptualizing and guiding the study of de-implementation. This scoping review sought to identify and characterize FM that can be used to study de-implementation as a phenomenon and identify gaps in the literature to inform future model development and application for research. METHODS: We searched nine databases and eleven journals from a broad array of disciplines (e.g., healthcare, public health, public policy) for de-implementation studies published between 1990 and June 2020. Two raters independently screened titles and abstracts, and then a pair of raters screened all full text records. We extracted information related to setting, discipline, study design, methodology, and FM characteristics from included studies. RESULTS: The final search yielded 1860 records, from which we screened 126 full text records. We extracted data from 27 articles containing 27 unique FM. Most FM (n = 21) were applicable to two or more levels of the Socio-Ecological Framework, and most commonly assessed constructs were at the organization level (n = 18). Most FM (n = 18) depicted a linear relationship between constructs, few depicted a more complex structure, such as a nested or cyclical relationship. Thirteen studies applied FM in empirical investigations of de-implementation, while 14 articles were commentary or review papers that included FM. CONCLUSION: De-implementation is a process studied in a broad array of disciplines, yet implementation science has thus far been limited in the integration of learnings from other fields. This review offers an overview of visual representations of FM that implementation researchers and practitioners can use to inform their work. Additional work is needed to test and refine existing FM and to determine the extent to which FM developed in one setting or for a particular topic can be applied to other contexts. Given the extensive availability of FM in implementation science, we suggest researchers build from existing FM rather than recreating novel FM. REGISTRATION: Not registered.

Demographic and Health Behavior Factors Associated With Clinical Trial Invitation and Participation in the United States.

Importance: Representative enrollment in clinical trials is critical to ensure equitable and effective translation of research to practice, yet disparities in clinical trial enrollment persist. Objective: To examine person-level factors associated with invitation to and participation in clinical trials. Design, Setting, and Participants: This cross-sectional study analyzed responses from 3689 US adults who participated in the nationally representative Health Information National Trends Survey, collected February through June 2020 via mailed questionnaires. Exposures: Demographic, clinical, and health behavior-related characteristics. Main Outcomes and Measures: History of invitation to and participation in a clinical trial, primary information sources, trust in information sources, and motives for participation in clinical trials were described. Respondent characteristics are presented as absolute numbers and weighted percentages. Associations between respondent demographic, clinical, and health behavior-related characteristics and clinical trial invitation and participation were estimated using survey-weighted logistic regression models. Results: The median (IQR) age of the 3689 respondents was 48 (33-61) years, and most were non-Hispanic White individuals (2063 [59%]; non-Hispanic Black, 452 [10%]; Hispanic, 521 [14%]), had more than a high school degree (2656 [68%]), were employed (1809 [58%]), and had at least 1 medical condition (2535 [61%]). Overall, 439 respondents (9%) had been invited to participate in any clinical trial. Respondents with increased odds of invitation were non-Hispanic Black compared with non-Hispanic White (adjusted odds ratio [aOR], 1.85; 95% CI, 1.13-3.02), had greater than a high school education compared with less than high school education (eg, ≥college degree: aOR, 4.84; 95% CI, 1.89-12.39), were single compared with married or living as married (aOR, 1.68; 95% CI, 1.04-2.73), and had at least 1 medical condition compared to none (eg, 1 medical condition: aOR, 2.25; 95% CI, 1.32-3.82). Respondents residing in rural vs urban areas had 77% decreased odds of invitation to a clinical trial (aOR 0.33; 95% CI 0.17-0.65). Of invited respondents, 199 (47%) participated. Compared with non-Hispanic White respondents, non-Hispanic Black respondents had 72% decreased odds of clinical trial participation (aOR, 0.28; 95% CI, 0.09-0.87). Respondents most frequently reported "health care providers" as the first and most trusted source of clinical trial information (first source: 2297 [59%]; most trusted source: 2597 [70%]). The most frequently reported motives for clinical trials participation were "wanting to get better" (2294 [66%]) and the standard of care not being covered by insurance (1448 [41%]). Conclusions and Relevance: The findings of this study suggest that invitation to and participation in clinical trials may differ by person-level demographic and clinical characteristics. Strategies toward increasing trial invitation and participation rates across diverse patient populations warrant further research to ensure equitable translation of clinical benefits from research to practice.

DeImplementing Ineffective and Low-Value Clinical Practices: Research and Practice Opportunities in Community Oncology Settings.

Patients, practitioners, and policy makers are increasingly concerned about the delivery of ineffective or low-value clinical practices in cancer care settings. Research is needed on how to effectively deimplement these types of practices from cancer care. In this commentary, we spotlight the National Cancer Institute Community Oncology Research Program (NCORP), a national network of community oncology practices, and elaborate on how it is an ideal infrastructure for conducting rigorous, real-world research on deimplementation. We describe key multilevel issues that affect deimplementation and also serve as a guidepost for developing strategies to drive deimplementation. We describe optimal study designs for testing deimplementation strategies and elaborate on how and why the NCORP network is uniquely positioned to conduct rigorous and impactful deimplementation trials. The number and diversity of affiliated community oncology care sites, coupled with the overall objective of improving cancer care delivery, make the NCORP an opportune infrastructure for advancing deimplementation research while simultaneously improving the care of millions of cancer patients nationwide.