Accelerated and interpretable oblique random survival forests

The oblique random survival forest (RSF) is an ensemble supervised learning method for right-censored outcomes. Trees in the oblique RSF are grown using linear combinations of predictors to create branches, whereas in the standard RSF, a single predictor is used. Oblique RSF ensembles often have higher prediction accuracy than standard RSF ensembles. However, assessing all possible linear combinations of predictors induces significant computational overhead that limits applications to large-scale data sets. In addition, few methods have been developed for interpretation of oblique RSF ensembles, and they remain more difficult to interpret compared to their axis-based counterparts. We introduce a method to increase computational efficiency of the oblique RSF and a method to estimate importance of individual predictor variables with the oblique RSF. Our strategy to reduce computational overhead makes use of Newton-Raphson scoring, a classical optimization technique that we apply to the Cox partial likelihood function within each non-leaf node of decision trees. We estimate the importance of individual predictors for the oblique RSF by negating each coefficient used for the given predictor in linear combinations, and then computing the reduction in out-of-bag accuracy. In general benchmarking experiments, we find that our implementation of the oblique RSF is approximately 450 times faster with equivalent discrimination and superior Brier score compared to existing software for oblique RSFs. We find in simulation studies that 'negation importance' discriminates between relevant and irrelevant predictors more reliably than permutation importance, Shapley additive explanations, and a previously introduced technique to measure variable importance with oblique RSFs based on analysis of variance. Methods introduced in the current study are available in the aorsf R package.Comment: 40 pages, 6 figure

The Dementia Care Study (D-Care): Recruitment Strategies and Demographic Characteristics of Participants in a Pragmatic Randomized Trial of Dementia Care

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare. METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients. RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), 58.4% were women, and 8.8% were Hispanic/Latino, and 11.9% were Black/African American. Caregivers were mostly children of the PLWD (46.5%) or spouses/partners (45.2%), 75.8% were women, 9.4% were Hispanic/Latino, and 11.6% were Black/African American. DISCUSSION: Health systems can successfully enroll diverse dyads in a pragmatic clinical trial

Patient Perspectives on a Targeted Text Messaging Campaign to Encourage Screening for Diabetes: Qualitative Study

BackgroundA sizeable proportion of prediabetes and diabetes cases among adults in the United States remain undiagnosed. Patient-facing clinical decision support (CDS) tools that leverage electronic health records (EHRs) have the potential to increase diabetes screening. Given the widespread mobile phone ownership across diverse groups, text messages present a viable mode for delivering alerts directly to patients. The use of unsolicited text messages to offer hemoglobin A1c (HbA1c) screening has not yet been studied. It is imperative to gauge perceptions of “cold texts” to ensure that information and language are optimized to promote engagement with text messages that affect follow-through with health behaviors. ObjectiveThis study aims to gauge the perceptions of and receptiveness to text messages to inform content that would facilitate engagement with text messages intended to initiate a mobile health (mHealth) intervention for targeted screening. Messages were designed to invite those not already diagnosed with diabetes to make a decision to take part in HbA1c screening and walk them through the steps required to perform the behavior based solely on an automated text exchange. MethodsIn total, 6 focus groups were conducted at Wake Forest Baptist Health (WFBH) between September 2019 and February 2020. The participants were adult patients without diabetes who had completed an in-person visit at the Family and Community Medicine Clinic within the previous year. We displayed a series of text messages and asked the participants to react to the message content and suggest improvements. Content was deductively coded with respect to the Health Belief Model (HBM) and inductively coded to identify other emergent themes that could potentially impact engagement with text messages. ResultsParticipants (N=36) were generally receptive to the idea of receiving a text-based alert for HbA1c screening. Plain language, personalization, and content, which highlighted perceived benefits over perceived susceptibility and perceived severity, were important to participants’ understanding of and receptiveness to messages. The patient-physician relationship emerged as a recurring theme in which patients either had a desire or held an assumption that their provider would be working behind the scenes throughout each step of the process. Participants needed further clarification to understand the steps involved in following through with HbA1c screening and receiving results. ConclusionsOur findings suggest that patients may be receptive to text messages that alert them to a risk of having an elevated HbA1c in direct-to-patient alerts that use cold texting. Using plain and positive language, integrating elements of personalization, and defining new processes clearly were identified by participants as modifiable content elements that could act as facilitators that would help overcome barriers to engagement with these messages. A patient’s relationship with their provider and the financial costs associated with texts and screening may affect receptiveness and engagement in this process

Concordance between clinical outcomes in the Systolic Blood Pressure Intervention Trial and in the electronic health record

BACKGROUND: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied. METHODS: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets. Among participants with available EHR data concurrent to trial-ascertained outcomes, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for EHR-recorded cardiovascular disease (CVD) events, using the gold standard of SPRINT-adjudicated outcomes (myocardial infarction (MI)/acute coronary syndrome (ACS), heart failure, stroke, and composite CVD events). We additionally compared the incidence of non-CVD adverse events (hyponatremia, hypernatremia, hypokalemia, hyperkalemia, bradycardia, and hypotension) in trial versus EHR data. RESULTS: 2468 SPRINT participants were included (mean age 68 (SD 9) years; 26% female). EHR data demonstrated ≥80% sensitivity and specificity, and ≥ 99% negative predictive value for MI/ACS, heart failure, stroke, and composite CVD events. Positive predictive value ranged from 26% (95% CI; 16%, 38%) for heart failure to 52% (95% CI; 37%, 67%) for MI/ACS. EHR data uniformly identified more non-CVD adverse events and higher incidence rates compared with trial ascertainment. CONCLUSIONS: These results support a role for EHR data collection in clinical trials, particularly for capturing laboratory-based adverse events. EHR data may be an efficient source for CVD outcome ascertainment, though there is clear benefit from adjudication to avoid false positives

Effect of Intensive versus Standard BP Control on AKI and Subsequent Cardiovascular Outcomes and Mortality: Findings from the SPRINT EHR Study

Background: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality. Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality. Results: A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD. Conclusions: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control

D-CARE: The Dementia Care Study: Design of a Pragmatic Trial of the Effectiveness and Cost Effectiveness of Health System-Based Versus Community-Based Dementia Care Versus Usual Dementia Care.

Background/objectivesAlthough several approaches have been developed to provide comprehensive care for persons living with dementia (PWD) and their family or friend caregivers, the relative effectiveness and cost effectiveness of community-based dementia care (CBDC) versus health system-based dementia care (CBDC) and the effectiveness of both approaches compared with usual care (UC) are unknown.DesignPragmatic randomized three-arm superiority trial. The unit of randomization is the PWD/caregiver dyad.SettingFour clinical trial sites (CTSs) based in academic and clinical health systems.ParticipantsA total of 2,150 English- or Spanish-speaking PWD who are not receiving hospice or residing in a nursing home and their caregivers.InterventionsEighteen months of (1) HSDC provided by a nurse practitioner or physician's assistant dementia care specialist who works within the health system, or (2) CBDC provided by a social worker or nurse care consultant who works at a community-based organization, or (3) UC with as needed referral to the Alzheimer's Association Helpline.MeasurementsPrimary outcomes: PWD behavioral symptoms and caregiver distress as measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Modified Caregiver Strain Index scales.Secondary outcomesNPI-Q Distress, caregiver unmet needs and confidence, and caregiver depressive symptoms. Tertiary outcomes: PWD long-term nursing home placement rates, caregiver-reported PWD functional status, cognition, goal attainment, "time spent at home," Dementia Burden Scale-Caregiver, a composite measure of clinical benefit, Quality of Life of persons with dementia, Positive Aspects of Caregiving, and cost effectiveness using intervention costs and Medicare claims.ResultsThe results will be reported in the spring of 2024.ConclusionD-CARE will address whether emphasis on clinical support and tighter integration with other medical services has greater benefit than emphasis on social support that is tied more closely to community resources. It will also assess the effectiveness of both interventions compared with UC and will evaluate the cost effectiveness of each intervention

The return of the Phoenix: the 1963 International Congress of Zoology and American zoologists in the twentieth century

This paper examines the International Congress of Zoology held in Washington D.C. in 1963 as a portrait of American zoologists’ search for effective and rewarding relationships with both each other and the public. Organizers of the congress envisioned the congress as a last ditch effort to unify the disparate subdisciplines of zoology, overcome the barriers of specialization, and ward off the heady claims of more reductionist biologists. The problems zoologists faced as they worked to fulfill these ambitious goals illuminate some of the challenges faced by members of the naturalist tradition as they worked to establish disciplinary unity while seeking public support in the competitive world of twentieth century science