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Introduction: Bayesian adaptive designs for clinical trials have gained popularity in the recent years due to the flexibility and efficiency that they offer. We consider the scenario where the outcome of interest comprises events with relatively low risk of occurrence and different case definitions resulting in varying control group risk assumptions. This is a scenario that occurs frequently for infectious diseases in global health research. Methods: We propose a Bayesian adaptive design that incorporates different case definitions of the outcome of interest that vary in stringency. A set of stopping rules are proposed where superiority and futility may be concluded with respect to different outcome definitions and therefore maintain a realistic probability of stopping in trials with low event rates. Through a simulation study, a variety of stopping rules and design configurations are compared. Results: The simulation results are provided in an interactive web application that allows the user to explore and compare the design operating characteristics for a variety of assumptions and design parameters with respect to different outcome definitions. The results for select simulation scenarios are provided in the article. Discussion: Bayesian adaptive designs offer the potential for maximizing the information learned from the data collected through clinical trials. The proposed design enables monitoring and utilizing multiple composite outcomes based on rare events to optimize the trial design operating characteristics.

To generate robust, demographically-adjusted regression-based norms for the Montreal Cognitive Assessment (MoCA) using a large sample of diverse older US adults. Baseline MoCA scores were examined for participants in the Systolic Blood Pressure Intervention Trial (SPRINT). A robust, cognitively-normal sample was drawn from individuals not subsequently adjudicated with cognitive impairment through 4 years of follow-up. Multivariable Beta-Binomial regression was used to model the association of demographic variables with MoCA performance and to create demographically-stratified normative tables. Participants' (N = 5,338) mean age was 66.9 ± 8.8 years, with 35.7% female, 63.1% White, 27.4% Black, 9.5% Hispanic, and 44.5% with a college or graduate education. A large proportion scored below published MoCA cutoffs: 61.4% scored below 26 and 29.2% scored below 23. A disproportionate number falling below these cutoffs were Black, Hispanic, did not graduate from college, or were ≥75 years of age. Multivariable modeling identified education, race/ethnicity, age, and sex as significant predictors of MoCA scores (p

In the SPRINT (Systolic Blood Pressure Intervention Trial), the number of strokes did not differ significantly by treatment group. However, stroke subtypes have heterogeneous causes that could respond differently to intensive blood pressure control. SPRINT participants (N=9361) were randomized to target systolic blood pressures of P =0.09). The interaction between baseline cardiovascular risk factor status and treatment arm on stroke risk did not reach significance ( P =0.05). Similar numbers of stroke subtypes occurred in the intensive BP control and standard control arms of SPRINT.

Background: In the SPRINT (Systolic Blood Pressure Intervention Trial), intensive BP treatment reduced acute decompensated heart failure (ADHF) events. Here, we report the effect on HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF) and their subsequent outcomes. Methods: Incident ADHF was defined as hospitalization or emergency department visit, confirmed, and formally adjudicated by a blinded events committee using standardized protocols. HFpEF was defined as EF ≥45%, and HFrEF was EF Results: Among the 133 participants with incident ADHF who had EF assessment, 69 (52%) had HFpEF and 64 (48%) had HFrEF ( P value: 0.73). During average 3.3 years follow-up in those who developed incident ADHF, rates of subsequent all-cause and HF hospital readmission and mortality were high, but there were no significant differences between those who developed HFpEF versus HFrEF. Randomization to the intensive arm had no effect on subsequent mortality or readmissions after the initial ADHF event, irrespective of EF subtype. During follow-up among participants who developed HFpEF, although relatively modest number of events limited statistical power, age was an independent predictor of all-cause mortality, and Black race independently predicted all-cause and HF hospital readmission. Conclusions: In SPRINT, intensive BP reduction decreased both acute decompensated HFpEF and HFrEF events. After initial incident ADHF, rates of subsequent hospital admission and mortality were high and were similar for those who developed HFpEF or HFrEF. Randomization to the intensive arm did not alter the risks for subsequent all-cause, or HF events in either HFpEF or HFrEF. Among those who developed HFpEF, age and Black race were independent predictors of clinical outcomes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062.

Rationale: Cognitive impairment after critical illness is common in observational studies of older intensive care unit (ICU) survivors. The rate of screening for and diagnosis of cognitive impairment in ICU survivors in nonresearch settings is unknown. Objectives: To determine how often cognitive impairment was detected in older adults in the year after critical illness at an academic medical center as part of 1) the Medicare Annual Wellness Visit (AWV) and 2) routine clinical care. Methods: This study was a retrospective cohort study conducted at an urban academic medical center. The study included 696 patients aged 65 years and older admitted to the medical ICU between October 1, 2016, and October 1, 2018, and discharged alive. Patients were also required to have a health system–affiliated primary care provider. Patients were followed for 1 year. We defined cognitive impairment detected in the AWV as either an indicated diagnosis of cognitive impairment or dementia or patient, family, or provider indication of memory concerns during the AWV. We modeled the incidence of AWV completion and the detection of cognitive impairment using semiparametric additive models accounting for the competing risk of death. Results: Over 1 year of follow-up, the cumulative incidence of mortality was 23.0% (95% confidence interval [CI], 19.9–26.1%), with 24.7% (95% CI, 21.5–27.9%) completing the AWV. The cumulative incidence of cognitive impairment first detected through the AWV was 3.4% (95% CI, 1.8–5.0%) at 1 year, with a higher cumulative incidence for diagnoses of cognitive impairment or dementia first indicated via encounter diagnosis codes or the electronic health record problem list (5.9%; 95% CI, 3.9–7.9%). Conclusions: The results of our study suggest that the currently implemented AWV is unlikely to be an adequate mechanism for detecting cognitive impairment in a high-risk population such as those recovering from critical illness.

BACKGROUND: Frailty is associated with numerous post-operative adverse outcomes in older adults. Current pre-operative frailty screening tools require additional data collection or objective assessments, adding expense and limiting large-scale implementation. OBJECTIVE: To evaluate the association of an automated measure of frailty integrated within the Electronic Health Record (EHR) with post-operative outcomes for nonemergency surgeries. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center. PARTICIPANTS: Patients 65 years or older that underwent nonemergency surgery with an inpatient stay 24 hours or more between October 8th, 2017 and June 1st, 2019. EXPOSURES: Frailty as measured by a 54-item electronic frailty index (eFI). OUTCOMES AND MEASUREMENTS: Inpatient length of stay, requirements for post-acute care, 30-day readmission, and 6-month all-cause mortality. RESULTS: Of 4,831 unique patients (2,281 females (47.3%); mean (SD) age, 73.2 (5.9) years), 4,143 (85.7%) had sufficient EHR data to calculate the eFI, with 15.1% categorized as frail (eFI > 0.21) and 50.9% pre-frail (0.10 < eFI ≤ 0.21). For all outcomes, there was a generally a gradation of risk with higher eFI scores. For example, adjusting for age, sex, race/ethnicity, and American Society of Anesthesiologists class, and accounting for variability by service line, patients identified as frail based on the eFI, compared to fit patients, had greater needs for post-acute care (odds ratio (OR) = 1.68; 95% confidence interval (CI) = 1.36–2.08), higher rates of 30-day readmission (hazard ratio (HR) = 2.46; 95%CI = 1.72–3.52) and higher all-cause mortality (HR = 2.86; 95%CI = 1.84–4.44) over 6 months’ follow-up. CONCLUSIONS: The eFI, an automated digital marker for frailty integrated within the EHR, can facilitate pre-operative frailty screening at scale.

Background Physical activity (PA) preserves mobility, but few practices screen older adults for mobility impairment or counsel on PA. Design "Promoting Active Aging" (PAA) was a mixed-methods randomized-controlled pilot, to test the feasibility and acceptability of a video-based PA counseling tool and implementation into practice of two mobility assessment tools. Setting Three primary care practices affiliated with Wake Forest Baptist Health. Participants Adults aged 65 years and older who presented for primary care follow-up and were willing and able to answer self-report questions and walk 4 meters (n = 59). Intervention Video-based PA counseling intervention versus control video, "Healthy Eating." Measurements Potential participants completed mobility assessments: self-report (Mobility Assessment Tool-short form (MAT-sf)) and performance based (4-meter walk test). We assessed PAA's implementation-feasibility, acceptability, and value-via interviews and surveys. Effectiveness was measured via participant attendance at a PA information session. Results Of 92 patients approached, 89 (96.7%) agreed to mobility assessment. Eighty-nine completed MAT-sf, and 97.8% (87/89) completed 4-meter walk test. Sixty-seven (75%) met eligibility criteria, and 59 (88%) consented to be randomized either to the PA counseling intervention (Video-PA) or to active control (Video-C). Most participants viewed the walk test positively (51/59; 86.4%). Staff reported that completion of patient surveys, MAT-sf, and videos required significant staff time and support (median = 26 minutes for all), resulting in low acceptability of MAT-sf and the videos. Attendance at a PA information session did not differ by randomization group (Video-PA = 11/29 (37.9%); Video-C = 12/30 (40%); 95% confidence interval for difference in proportion = -0.29 to 0.25). Conclusions Mobility assessment, particularly a 4-meter walk test, was feasible in primary care. Tablet-based assessment (MAT-sf) and video counseling tools, selected to reduce staff effort, instead required significant time to implement. Future work to promote PA should identify effective ways to facilitate adoption of PA in sedentary older adults that do not burden staff.

Advance care planning (ACP), especially among vulnerable older adults, remains underused in primary care. Additionally, many ACP initiatives fail to integrate directly into the electronic health record (EHR), resulting in infrequent and disorganized documentation.To determine whether a nurse navigator-led ACP pathway combined with a health care professional-facing EHR interface improves the occurrence of ACP discussions and their documentation within the EHR.This was a randomized effectiveness trial using the Zelen design, in which patients are randomized prior to informed consent, with only those randomized to the intervention subsequently approached to provide informed consent. Randomization began November 1, 2018, and follow-up concluded November 1, 2019. The study population included patients 65 years or older with multimorbidity combined with either cognitive or physical impairments, and/or frailty, assessed from 8 primary care practices in North Carolina.Participants were randomized to either a nurse navigator-led ACP pathway (n = 379) or usual care (n = 380).The primary outcome was documentation of a new ACP discussion within the EHR. Secondary outcomes included the usage of ACP billing codes, designation of a surrogate decision maker, and ACP legal form documentation. Exploratory outcomes included incident health care use.Among 759 randomized patients (mean age 77.7 years, 455 women [59.9%]), the nurse navigator-led ACP pathway resulted in a higher rate of ACP documentation (42.2% vs 3.7%, P .001) as compared with usual care. The ACP billing codes were used more frequently for patients randomized to the nurse navigator-led ACP pathway (25.3% vs 1.3%, P .001). Patients randomized to the nurse navigator-led ACP pathway more frequently designated a surrogate decision maker (64% vs 35%, P .001) and completed ACP legal forms (24.3% vs 10.0%, P .001). During follow-up, the incidence of emergency department visits and inpatient hospitalizations was similar between the randomized groups (hazard ratio, 1.17; 95% CI, 0.92-1.50).A nurse navigator-led ACP pathway integrated with a health care professional-facing EHR interface increased the frequency of ACP discussions and their documentation. Additional research will be required to evaluate whether increased EHR documentation leads to improvements in goal-concordant care.ClinicalTrials.gov Identifier: NCT03609658.

The current standard of care for the prevention and treatment of scarring after burn injury is pressure garment therapy. Although this therapy has been used clinically for many years, controversy remains regarding its efficacy. The authors evaluated the efficacy of pressure garment therapy in a female red Duroc pig burn model in which wound depth could be tightly controlled.Full-thickness burn wounds were generated on female red Duroc pigs. At day 28 after burn, pressure garment therapy was applied to half the wounds (10 mmHg), with control wounds covered with garments that exerted no compression. Scar area, perfusion, hardness, and elasticity were quantified at days 0, 28, 42, 56, and 72 using computerized planimetry, laser Doppler, and torsional ballistometry. Scar morphology was assessed at days 28, 56, and 76 using histology, immunohistochemistry, and transmission electron microscopy.Pressure garment therapy significantly hindered scar contraction, with control scars contracting to 64.6 percent + 13.9 percent original area at day 72, whereas pressure garment therapy scars contracted to 82.7 percent + 17.9 percent original area. Pressure garments significantly reduced skin hardness and increased skin strength by 1.3 times. No difference in perfusion or blood vessel density was observed. The average collagen fiber diameter was greater in control burns than in pressure garment therapy.Pressure garment therapy was effective at reducing scar contraction and improving biomechanics compared with control scars. These results confirm the efficacy of pressure garments and highlight the need to further investigate the role of pressure magnitude and the time of therapy application to enhance efficacy for optimal biomechanics and patient mobility.