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BackgroundHypertension is a major cause of cardiovascular disease. The Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP). However, adherence is typically low. Mindfulness training adapted to improving health behaviors that lower BP could improve DASH adherence, in part through improved interoceptive awareness relevant to dietary consumption. The primary objective of the MB-BP trial was to evaluate effects of the Mindfulness-Based Blood Pressure Reduction (MB-BP) program on interoceptive awareness. Secondary objectives assessed whether MB-BP impacts DASH adherence, and explored whether interoceptive awareness mediates DASH dietary changes.MethodsParallel-group phase 2 randomized clinical trial conducted from June 2017-November 2020 with 6 months follow-up. Data analyst was blinded to group allocation. Participants had elevated unattended office BP (≥120/80 mmHg). We randomized 201 participants to MB-BP (n=101) or enhanced usual care control (n=100). Loss-to-follow-up was 11.9%. Outcomes were the Multidimensional Assessment of Interoceptive Awareness (MAIA; range 0-5) score, and the DASH adherence score (range 0-11) assessed via a 163-item Food Frequency Questionnaire.ResultsParticipants were 58.7% female, 81.1% non-Hispanic white, with mean age 59.5 years. Regression analyses demonstrated that MB-BP increased the MAIA score by 0.54 (95% CI: 0.35,0.74; pConclusionsA mindfulness training program adapted to improving health behaviors that lower BP improved interoceptive awareness and DASH adherence. MB-BP could support DASH dietary adherence in adults with elevated BP.Clinical Trial RegistrationClinicaltrials.govidentifierNCT03859076(https://clinicaltrials.gov/ct2/show/NCT03859076; MAIA) andNCT03256890(https://clinicaltrials.gov/ct2/show/NCT03256890; DASH diet adherence).

ImportanceLow-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in patients undergoing LDCT lung screening. However, the exact nature of these SIF findings has not been described.ObjectiveTo describe SIFs reported in the LDCT arm of the National Lung Screening Trial and classify SIFs as reportable or not reportable to the referring clinician (RC) using the American College of Radiology’s white papers on incidental findings.Design, Setting, and ParticipantsThis was a retrospective case series study of 26 455 participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT. The trial was conducted from 2002 to 2009, and data were collected at 33 US academic medical centers.Main Outcomes and MeasuresSignificant incident findings were defined as a final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer or a positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm.ResultsOf 26 455 participants, 10 833 (41.0%) were women, the mean (SD) age was 61.4 (5.0) years, and there were 1179 (4.5%) Black, 470 (1.8%) Hispanic/Latino, and 24 123 (91.2%) White individuals. Participants were scheduled to undergo 3 screenings during the course of the trial; the present study included 75 126 LDCT screening examinations performed for 26 455 participants. A SIF was reported for 8954 (33.8%) of 26 455 participants who were screened with LDCT. Of screening tests with a SIF detected, 12 228 (89.1%) had a SIF considered reportable to the RC, with a higher proportion of reportable SIFs among those with a positive screen result for lung cancer (7632 [94.1%]) compared with those with a negative screen result (4596 [81.8%]). The most common SIFs reported included emphysema (8677 [43.0%] of 20 156 SIFs reported), coronary artery calcium (2432 [12.1%]), and masses or suspicious lesions (1493 [7.4%]). Masses included kidney (647 [3.2%]), liver (420 [2.1%]), adrenal (265 [1.3%]), and breast (161 [0.8%]) abnormalities. Classification was based on free-text comments; 2205 of 13 299 comments (16.6%) could not be classified. The hierarchical reporting of final diagnosis in NLST may have been associated with an overestimate of severe emphysema in participants with a positive screen result for lung cancer.Conclusions and RelevanceThis case series study found that SIFs were commonly reported in the LDCT arm of the National Lung Screening Trial, and most of these SIFs were considered reportable to the RC and likely to require follow-up. Future screening trials should standardize SIF reporting.

BACKGROUND: The correlations between skilled nursing facility (SNF) admissions, number of hospitalizations, and informal caregiving hours received after adjusting for physical and cognitive function and sociodemographic covariates are not well understood. OBJECTIVE: To better understand risk factors for SNF admissions and the interrelation with hospitalizations and amount of informal caregiving received, this study applied a novel joint modeling analysis to simultaneously explore the correlation and shared information between the three outcomes. RESEARCH DESIGN: Observational follow-up study. SUBJECTS: Data from 4836 older Americans included in the 2011–2015 rounds of the National Health and Aging Trends Study were linked with Centers for Medicare & Medicaid Services. MEASURES: We jointly modeled SNF admission, hospital admissions, and informal caregiving hours received while accounting for possible risk factors. We addressed missing values by multiple imputation with chained equations. RESULTS: SNF admission evidenced a strong positive correlation with hospital admission and SNF admission evidenced a weak positive correlation with the informal caregiving hours received after adjustment for important risk factors. Non-Hispanic white race/ethnicity, living alone, not being Medicaid eligible, Alzheimer’s disease and related dementias diagnosis, activities of daily living disabilities, and frailty were associated with increased risk of SNF admissions and any/number of hospital admission. Lower educational level was also associated with the latter. Medicaid eligibility was the only factor not associated with any nor numbers of informal caregiving hours received. CONCLUSIONS: Sociodemographic and health factors were important for predicting SNF admissions. After adjustment for important risk factors, SNF evidenced a strong positive correlation with the number of hospitalizations and a weak positive correlation with the hours of informal caregiving received.

Objectives As the US tests models of care for the seriously ill, patient perceptions of the quality of care are important. Proxies are often needed for this group. We sought to understand the potential impact of proxy reports for the assessment of care quality and experience in cancer. Methods Secondary data analysis of a deidentified prospective study that included surveys of perceived care quality, including symptom management, from patients with advanced cancer receiving chemotherapy and their caregivers. Surveys were administered at diagnosis (time 1) and treatment (time 2), with top-box scoring used for analysis. Overall concordance was assessed using metrics including Gwet’s AC1. The proportion of the highest scores by respondent type within 2 subgroups were examined: (1) symptom burden and (2) practice setting. Results Data from 83 dyads were analyzed. Proxies and patients frequently reported the highest scores for quality (time 1: proxies: 77% and patients: 80%). At time 1, 14% of proxies and 10% of patients reported an unmet need for symptom palliation. Most patients reporting an unmet need gave the top score for quality (75%), but fewer proxies did so (45%). Proxy and patient reports were similar within practice settings. Concordance was at least moderate (nearly all outcomes >0.5 and some >0.8) by Gwet’s AC1. Significance of results Findings of at least moderate concordance and similar experience outcomes within subgroups suggest the use of proxies may not change estimates substantially. However, consideration should be taken when evaluating symptom management, particularly if such evaluations inform assessment of provider performance.

AIMS Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycaemia-mediated declines in cognitive and physical functioning compared with sulphonylureas (SUs), yet comparative studies are unavailable among older adults, particularly nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents. MATERIALS AND METHODS This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after 1:1 propensity score matching using Cox regression models. RESULTS The matched cohort (N = 1784) had a mean ± SD age of 80 ± 8 years and 73% were women. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared with SU users, DPP4I users had lower 180-day rates of cognitive decline [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.31-1.19], altered mental status events (HR = 0.71, 95% CI 0.39-1.27), and functional decline (HR = 0.89, 95% CI 0.51-1.56), but estimates were imprecise. CONCLUSIONS Rates of cognitive and functional decline may be reduced among older NH residents using DPP4Is compared with SUs, but larger studies with greater statistical power should resolve the remaining uncertainty by providing more precise effect estimates.

Background Studies comparing dipeptidyl peptidase-4 inhibitors (DPP4Is) to sulfonylureas (SUs) are unavailable for frail older adults, especially nursing home (NH) residents. We examined the effects of DPP4Is versus SUs on severe adverse glycemic events, cardiovascular events, and death among NH residents. Methods We conducted a national retrospective cohort study of long-stay NH residents aged ≥65 years using 2008-2010 national US Minimum Data Set clinical assessment data and linked Medicare claims. Exposure was new DPP4I versus new SU use assessed via Medicare Part D drug claims. One-year outcomes were severe hypoglycemia, severe hyperglycemia, acute myocardial infarction (AMI), heart failure (HF), major adverse cardiovascular events plus HF (MACE+HF), and death. We compared outcomes after propensity score matching using Cox proportional hazards regression models. Results The cohort (N = 2016) had a mean (SD) age of 81 (8.1) years and was 72% female. Compared with SU users, DPP4I users had a lower 1-year rate of severe hypoglycemic events (HR = 0.57, 95% CI 0.34-0.94), but statistically similar rates of severe hyperglycemic events (HR = 0.94, 95% CI 0.52-1.72), AMI (HR = 0.76, 95% CI 0.44-1.30), HF (HR = 1.01, 95% CI 0.79-1.30), MACE+HF (HR = 0.90, 95% CI 0.72-1.12), and death (HR = 0.97, 95% CI 0.86-1.10). Conclusions DPP4Is should be a preferred treatment option over SUs for NH residents and other frail older adults given the importance of avoiding hypoglycemia.

In cluster randomized trials (CRTs) groups rather than individuals are randomized to different interventions. Individuals’ responses within clusters are commonly more similar than those across clusters. This dependency introduces complexity when calculating the number of clusters required to reach a specified statistical power for nominal significance levels and effect sizes. Current CRTs’ sample size estimation approaches rely on asymptotic-based formulae or Monte Carlo methods. We propose a new Monte Carlo procedure which is based on the potential outcomes framework. By explicitly defining the causal estimand, the data generating, the sampling, and the treatment assignment mechanisms, this procedure allows for sample size calculations in a broad range of study designs including sample size calculations in finite and infinite populations. It can also address financial and administrative considerations by allowing for unequal allocation of clusters. The R package CRTsampleSearch implements the method and we provide examples for using this package.

Introduction Older adults comprise an increasingly large proportion of patients with traumatic brain injury (TBI) receiving care in inpatient rehabilitation facilities (IRF). However, high rates of comorbidities and evidence of declining preinjury health among older adults who sustain TBI raise questions about their ability to benefit from IRF care. Objective 1) describe the proportion of older adults with TBI who exhibited minimal detectable change (MDC) and a minimally clinically important difference (MCID) in motor function from IRF admission to discharge; and 2) identify characteristics associated with clinically meaningful improvement in motor function and better discharge functional status. Design In this retrospective cohort study, we utilized Medicare administrative data probabilistically linked to the National Trauma Data Bank to estimate the proportion of patients whose motor function improved during inpatient rehabilitation and identify factors associated with meaningful improvement in motor function and motor function at discharge. Setting Inpatient rehabilitation facilities in the US. Patients Fee-for-service Medicare beneficiaries with TBI. Main outcome measures Minimal Detectable Change (MDC) and Minimally Clinically Important Difference (MCID) in the Functional Independence Measure motor (FIM-M) score from admission to discharge, and FIM-M score at IRF discharge. Results From IRF admission to discharge 84% of patients achieved the MDC threshold, and 68% of patients achieved the MCID threshold for FIM-M scores. Factors associated with a higher probability of achieving the MCID for FIM-M scores included better admission motor and cognitive function, lower comorbidity burden, and a length of stay longer than 10 days but only among individuals with lower admission motor function. Older age was associated with a lower FIM-M discharge score, but not the probability of achieving the MCID in FIM-M score. Conclusion Older adults with TBI have the potential to improve their motor function with IRF care. Baseline functional status and comorbidity burden, rather than acute injury severity, should be used to guide care planning. This article is protected by copyright. All rights reserved.

The International Council for Harmonisation (ICH) recently published an E9(R1) addendum that requires the estimand associated with the study objective in clinical trials to be clearly defined. One of the challenges in defining an estimand is the estimand’s handling of intercurrent events (ICEs) that affect the collection or interpretation of the data for the study. Among the strategies for handling ICEs, sponsors may prefer to examine hypothetical strategies that assess the theoretical or attributable efficacy of test drugs or biologic products. We first look at several estimands under different hypothetical treatment conditions of interest. For these estimands, the data after ICEs are ignored and treated as missing. Analyses are carried out with missing data assumptions under missing at random, control-based imputation, and return-to-baseline imputation. With the explicit forms of these hypothetical estimands derived, we investigate Bayesian approaches to obtain corresponding point and interval estimates and propose a Bayesian sensitivity analysis which avoids the information positive problem. The methods are illustrated with applications to three clinical trials.

Unblinded trials are common in oncology, but patient knowledge of treatment assignment may bias response to questionnaires. We sought to ascertain the extent of possible bias arising from patient knowledge of treatment assignment.This is a retrospective analysis of data from 2 randomized trials in multiple myeloma, 1 double-blind and 1 open label. We compared changes in patient reports of symptoms, function, and health status from prerandomization (screening) to baseline (pretreatment but postrandomization) across control and investigational arms in the 2 trials. Changes from prerandomization scores at ~2 and 6 months on treatment were evaluated only across control arms to avoid comparisons between 2 different experimental drugs. All scores were on 0- to 100-point scales. Inverse probability weighting, entropy balancing, and multiple imputation using propensity score splines were used to compare score changes across similar groups of patients.Minimal changes from screening were seen at baseline in all arms. In the control arm, mean changes of7 points were seen for all domains at 2 and 6 months. The effect of unblinding at 6 months in social function was a decline of less than 6 points (weighting: -3.09; 95% confidence interval -8.41 to 2.23; balancing: -4.55; 95% confidence interval -9.86 to 0.76; imputation: -5.34; 95% confidence interval -10.64 to -0.04).In this analysis, we did not find evidence to suggest that there was a meaningful differential effect on how patients reported their symptoms, function or health status after knowing their treatment assignment.

Estimating relationships between multiple incomplete patient measurements requires methods to cope with missing values. Multiple imputation is one approach to address missing data by filling in plausible values for those that are missing. Multiple imputation procedures can be classified into two broad types: joint modeling (JM) and fully conditional specification (FCS). JM fits a multivariate distribution for the entire set of variables, but it may be complex to define and implement. FCS imputes missing data variable-by-variable from a set of conditional distributions. In many studies, FCS is easier to define and implement than JM, but it may be based on incompatible conditional models. Imputation methods based on multilevel modeling show improved operating characteristics when imputing longitudinal data, but they can be computationally intensive, especially when imputing multiple variables simultaneously. We review current MI methods for incomplete longitudinal data and their implementation on widely accessible software. Using simulated data from the National Health and Aging Trends Study, we compare their performance for monotone and intermittent missing data patterns. Our simulations demonstrate that in a longitudinal study with a limited number of repeated observations and time-varying variables, FCS-Standard is a computationally efficient imputation method that is accurate and precise for univariate single-level and multilevel regression models. When the analyses comprise multivariate multilevel models, FCS-LMM-latent is a statistically valid procedure with overall more accurate estimates, but it requires more intensive computations. Imputation methods based on generalized linear multilevel models can lead to biased subject-level variance estimates when the statistical analyses involve hierarchical models.

This article aimed to develop a predictive model to identify persons with recent gestational diabetes mellitus (GDM) most likely to progress to impaired glucose tolerance postpartum. We conducted an observational study among persons with GDM in their most recent pregnancy, defined by Carpenter-Coustan criteria. Participants were followed up from delivery through 1-year postpartum. We used lasso regression with k-fold cross validation to develop a multivariable model to predict progression to impaired glucose tolerance, defined as HbA1c≥5.7%, at 1-year postpartum. Predictive ability was assessed by the area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Of 203 participants, 71 (35%) had impaired glucose tolerance at 1-year postpartum. The final model had an AUC of 0.79 (95% confidence interval [CI]: 0.72, 0.85) and included eight indicators of weight, body mass index, family history of type 2 diabetes, GDM in a prior pregnancy, GDM diagnosis24 weeks' gestation, and fasting and 2-hour plasma glucose at 2 days postpartum. A cutoff point of ≥ 0.25 predicted probability had sensitivity of 80% (95% CI: 69, 89), specificity of 58% (95% CI: 49, 67), PPV of 51% (95% CI: 41, 61), and NPV of 85% (95% CI: 76, 91) to identify women with impaired glucose tolerance at 1-year postpartum. Our predictive model had reasonable ability to predict impaired glucose tolerance around delivery for persons with recent GDM.· We developed a predictive model to identify persons with GDM most likely to develop IGT postpartum.. · The final model had an AUC of 0.79 (95% CI: 0.72, 0.85) and included eight clinical indicators.. · If validated, our model could help prioritize diabetes prevention efforts among persons with GDM..

OBJECTIVE: To compare rates of incident SARS-CoV-2 infection and 30-day hospitalization or death among residents with confirmed infection in nursing homes with earlier versus later SARS-CoV-2 vaccine clinics. DESIGN: Matched pairs analysis of nursing homes that had their initial vaccine clinics between December 18, 2020, and January 2, 2021, versus between January 3, 2021, and January 18, 2021. Matched facilities had their initial vaccine clinics between 12 and 16 days apart. SETTING AND PARTICIPANTS: Two hundred and eighty nursing homes in 21 states owned and operated by the largest long-term care provider in the United States. MEASUREMENTS: Incident SARS-CoV-2 infections per 100 at-risk residents per week; hospital transfers and/or deaths per 100 residents with confirmed SARS-CoV-2 infection per day, averaged over a week. RESULTS: The early vaccinated group included 136 facilities with 12,157 residents; the late vaccinated group included 144 facilities with 13,221 residents. After 1 week, early vaccinated facilities had a predicted 2.5 fewer incident SARS-CoV-2 infections per 100 at-risk residents per week (95% CI: 1.2-4.0) compared with what would have been expected based on the experience of the late vaccinated facilities. The rates remained significantly lower for several weeks. Cumulatively over 5 weeks, the predicted reduction in new infections was 5.2 cases per 100 at-risk residents (95% CI: 3.2-7.3). By 5 to 8 weeks post-vaccine clinic, early vaccinated facilities had a predicted 1.1 to 3.8 fewer hospitalizations and/or deaths per 100 infected residents per day, averaged by week than expected based on late vaccinated facilities' experience for a cumulative on average difference of 5 events per 100 infected residents per day. CONCLUSIONS: The SARS-CoV-2 vaccines seem to have accelerated the rate of decline of incident infections, morbidity, and mortality in this large multi-state nursing home population.

OBJECTIVE To identify patient, injury, and functional status characteristics associated with successful discharge to the community following a skilled nursing facility (SNF) stay among older adults hospitalized following traumatic brain injury (TBI). SETTING Skilled nursing facilities. PARTICIPANTS Medicare fee-for-service beneficiaries admitted to an SNF after hospitalization for TBI. DESIGN Retrospective cohort study using Medicare administrative data merged with the National Trauma Data Bank using a multilayered Bayesian record linkage approach. MAIN OUTCOME MEASURE Successful community discharge: discharged alive within 100 days of SNF admission and remaining in the community for 30 days or more without dying or admission to a healthcare facility. RESULTS Medicaid enrollment, incontinence, decreased independence with activities of daily living, and cognitive impairment were associated with lower odds of successful discharge, whereas race "other" was associated with higher odds of successful discharge. Injury factors including worse injury severity (Glasgow Coma Scale and Abbreviated Injury Scale scores) and fall-related injury mechanism were not associated with successful discharge. CONCLUSION Among older adults with TBI who discharge to an SNF, sociodemographic and functional status characteristics are associated with successful discharge and may be useful to clinicians for discharge planning. Acute injury severity indices may have limited utility in predicting discharge disposition once a patient is admitted to an SNF for post-acute care.

Circadian disruptions precede high-fat diet (HFD)-induced obesity (DIO). Deviation of the endogenous circadian rhythm period length (tau) from 24 hours correlates with mice inter-strain DIO under t...

Background/objectives To assess whether an advance care planning (ACP) video intervention impacts care among short-stay nursing home (NH) patients. Design PRagmatic trial of Video Education in Nursing Homes (PROVEN) was a pragmatic cluster randomized clinical trial. Setting A total of 360 NHs (N = 119 intervention, N = 241 control) owned by two healthcare systems. Participants A total of 2,538 and 5,290 short-stay patients with advanced dementia or cardiopulmonary disease (advanced illness) in the intervention and control arms, respectively; 23,302 and 50,815 short-stay patients without advanced illness in the intervention and control arms, respectively. Intervention Five ACP videos were available on tablets or online. Designated champions at each intervention facility were instructed to offer a video to patients (or proxies) on admission. Control facilities used usual ACP practices. Measurements Follow-up time was at most 100 days for each patient. Outcomes included hospital transfers per 1000 person-days alive and the proportion of patients experiencing more than one hospital transfer, more than one burdensome treatment (tube-feeding, parenteral therapy, invasive mechanical intervention, and intensive care unit admission), and hospice enrollment. Champions recorded whether a video was offered in the patients' electronic medical record. Results There was no significant reduction in hospital transfers per 1000 person-days alive in the intervention versus control groups with advanced illness (rate (95% confidence interval (CI)), 12.3 (11.6-13.1) vs 13.2 (12.5-13.7); rate difference: -0.8; 95% CI = -1.8-0.2)). There was a nonsignificant reduction in hospital transfers per 1000 person-days alive in the intervention versus control among short-stay patients without advanced illness. Secondary outcomes did not differ between groups among patients with and without advanced illness. Based on champion only reports 14.2% and 15.3% of eligible short-stay patients with and without advanced illness were shown videos, respectively. Conclusion An ACP video program did not significantly reduce hospital transfers, burdensome treatment, or hospice enrollment among short-stay NH patients; however, fidelity to the intervention was low.

Obesity reduces the quality of life and life expectancy, whereas nonoperative interventions have shown poor results so far. Statins effectively combat hypercholesterolemia but are not well tolerated at high doses, raising the need for coprescription with cholesterol sorbents and/or absorption inhibitors. Montmorillonite (MMT) clay was found to attenuate hypercholesterolemia and obesity by reducing cholesterol and fat absorption. However, acicular clay-like sepiolite may offer better results due to its more substantial adsorption of nonpolar molecules. We herein aimed at (1) assessing in vitro the capacity of sepiolite to adsorb edible oil and cholesterol compared with that of MMT and (2) assessing in vivo the effect of continuous feeding on a high-fat high-cholesterol diet (HFD) (53.6% w/w fat and 0.2% cholesterol) supplemented with 5% (w/w) edible sepiolite, on diet-induced obesity rate, hypercholesterolemia, and hyperlipidemia. Fourier transform infrared spectroscopy showed in vitro that sepiolite adsorption of olive oil and cholesterol was five to eight times greater than that of MMT clay. Sepiolite supplementation to HFD fed to mature mice for 12.5 weeks resulted in lower total blood cholesterol and triacylglycerol levels and attenuated body weight gain, by reducing fat gain. Sepiolite supplementation did not affect energy intake but increased fecal extraction of sterols and lipids, without notable side effects. These results demonstrate that supplementing a HFD with sepiolite attenuates gastrointestinal absorption of dietary lipids and sterols, thus mitigating obesity, hyperlipidemia, and hypercholesterolemia. Further exploration of the efficacy, mechanism of action, and safety of sepiolite as a food supplement for combating the metabolic syndrome is needed.

BACKGROUND: Home-delivered meals promote food security, socialization, and independence among homebound older adults. However, it is unclear which of the two predominant modes of meal delivery, daily-delivered vs. drop-shipped, frozen meals, promotes community living for homebound older adults with dementia. Our objective is to present the protocol for a pilot multisite, two-arm, pragmatic feasibility trial comparing the effect of two modes of meal delivery on nursing home placement among people with dementia. We include justifications for individual randomization with different consent processes and waivers for specific elements of the trial. METHODS: 236 individuals with dementia on waiting lists at three Meals on Wheels programs’ in Florida and Texas will be randomized to receive either: 1) meals delivered multiple times per week by a Meals on Wheels volunteer or paid driver who may socialize with and provide an informal wellness check or 2) frozen meals that are mailed to participants’ homes every two weeks. We will evaluate and refine processes for recruitment and randomization; assess adherence to the intervention; identify common themes in participant experience; and test processes for linking participant data with Medicare records and nursing home assessment data. We will conduct exploratory analyses examining time to nursing home placement, the primary outcome for the larger trial. CONCLUSION: This pilot will inform the follow-on large-scale, definitive pragmatic trial. In addition, the justifications for individual randomization with differing consent procedures for elements of a pragmatic trial provide a model for future trialists looking to develop ethical and feasible pragmatic studies enrolling people with dementia.

Fatty acid levels vary between day and night milking. Many dairy cows are kept under whole light at night (LAN) illumination using a white light-emitting diode (W-LED) suspected of disrupting circadian rhythms. We investigated the effect of W-LED LAN and same lux level red LED (R-LED) LAN, which is known not to disrupt circadian rhythms in other mammals, on milk yield and circadian composition, compared to a natural light-dark (LD)-cycle of 10-11 h light. Cows under the natural LD-cycle showed circadian variation in milk-fat composition, characterized by higher health-promoting monounsaturated fatty acid (MUFA) and lower saturated fatty acid (SFA) levels in 13:30-h (day milk, DM) than 03:30-h (night milk, NM). W-LED did not affect milk and milk-fat yields, yet abolished the circadian pattern of milk-fat composition towards a less healthy fatty acid profile by lowering MUFA levels of DM. Switching W-LED to R-LED reversed these circadian disruptions. Therefore, R-LED and W-LED have no commercial advantage over the tested LD-cycle, while W-LED is disadvantageous, showing a circadian disruption. Accordingly, if the illumination is indispensable, the R-LED regime is preferable over W-LED for cow’s wellbeing and for preserving the natural milk-fat profile; while differentiating DM from NM from a commercial-health-promoting perspective.

Missing data are common in empirical studies. Multiple imputation is a method to handle missing values by replacing them with plausible values. A common imputation method is multiple imputation with chain equations (MICE). MICE defines a series of conditional distributions to impute missing values. Although MICE is relatively easy to implement, it may not converge to a proper joint distribution. An alternative strategy is to model the variables jointly using the general location model, but this model can become complex when the number of variables increases. Both approaches require integration of prior information when there are more variables than cases. We propose a Bayesian model that is based on the singular value decomposition components of a continuous data matrix to impute missing values. The model assumes that the matrix is of low rank by applying double exponential prior distributions on the singular values. We describe an efficient sampling algorithm to estimate the model’s parameters and impute the missing data. The performance of the model is compared to current imputation methods in simulated and real datasets. Of all the methods considered and in most of the simulated and real datasets, the proposed procedure appears to be the most accurate and precise. Supplementary materials for this article are available online.

Background: Blinding is a cornerstone of trial methodology. Prior work indicates participant-perceived assignment may be associated with trial outcomes. Less is known about how perception changes over time and if this is associated with outcomes. Objectives: To evaluate if participants change their perception of assignment over time in a blinded trial, and if perception is associated with different types of patient-reported outcomes (PROs). Methods: This was a secondary analysis of data from the Achieving Cannabis Cessation-Evaluating N-Acetylcysteine Treatment (ACCENT) trial, which evaluated the efficacy of N-acetylcysteine (NAC) relative to placebo for treating cannabis use disorder. Participants (N = 234; 164 men, 70 women) were asked at weeks 5 and 9 what treatment (placebo or NAC) they believed they were receiving. We included PROs proximal (cannabis-associated problems, craving) and distal (anxiety) to the intervention. Analysis was by multiple linear regression and mixed models. Results: Approximately 20% of participants in both arms changed their perception over time. Relative to participants who consistently perceived assignment to placebo, participants who consistently perceived assignment to NAC did not always have comparatively better average scores (coefficient −3.3 [95% CI: −7.0, 0.5]). In some analyses, participants who switched to guessing NAC from placebo had comparatively better average scores (coefficient −3.0 [95% CI: −9.3, 3.4]), but this was inconsistent across outcomes or strata defined by actual assignment or guess accuracy. Conclusion: The study suggests that the proportion of individuals who switch their perception over time is modest. However, this group may influence the estimates of intervention effects on some PROs.

Patient-reported outcome and experience measures are increasingly important in health care and health research. The use of these measures is growing in the US and overseas, and performance measures that incorporate patient-reported outcomes are being considered, particularly in cancer. A major challenge for the use of these measures is patient non-response, especially for diseases such as cancer and dementia. A commonly used approach is to ask a proxy such as the patient’s spouse or child to complete the measure on their behalf. Proxy reporting is used in major surveys, including those used in pay-for-performance approaches. No standards exist regarding how to adjust for the use of proxy-reported measures in analyses. As patients requiring proxies likely differ in important ways from those who can self-report, adjusting for these differences is important. In this paper, we evaluate the use of propensity score models when adjusting for proxy-reported data, including weighting, matching with replacement, and non-parametric multiple imputation. Additionally, because previous analyses using propensity scores for proxy reports have employed stepwise or p value based algorithms, we evaluated the sensitivity of our results to the inclusion of respondent-sensitive variables such as proxy reports of patient health status, as well as auxiliary covariates. Under all propensity score methods, estimates obtained from propensity scores using respondent-insensitive variables were different from those obtained when respondent-sensitive variables were incorporated in the propensity score. Propensity score methods have limitations in these contexts and their assumptions should be carefully examined.

Background Prior studies have identified lower mortality in Black Veterans compared with White Veterans after hospitalization for common medical conditions, but these studies adjusted for comorbid conditions identified in administrative claims. Objectives The objectives of this study were to compare mortality for non-Hispanic White (hereafter, "White"), non-Hispanic Black (hereafter, "Black"), and Hispanic Veterans hospitalized for heart failure (HF) and pneumonia and determine whether observed mortality differences varied according to whether claims-based comorbid conditions and/or clinical variables were included in risk-adjustment models. Research design This was an observational study. Subjects The study cohort included 143,520 admissions for HF and 127,782 admissions for pneumonia for Veterans hospitalized in 132 Veterans Health Administration (VA) Medical Centers between January 2009 and September 2015. Measures The primary independent variable was racial/ethnic group (ie, Black, Hispanic, and non-Hispanic White), and the outcome was all-cause mortality 30 days following admission. To compare mortality by race/ethnicity, we used logistic regression models that included different combinations of claims-based, clinical, and sociodemographic variables. For each model, we estimated the average marginal effect (AME) for Black and Hispanic Veterans relative to White Veterans. Results Among the 143,520 (127,782) hospitalizations for HF (pneumonia), the average patient age was 71.6 (70.9) years and 98.4% (97.1%) were male. The unadjusted 30-day mortality rates for HF (pneumonia) were 7.2% (11.0%) for White, 4.1% (10.4%) for Black and 8.4% (16.9%) for Hispanic Veterans. Relative to White Veterans, when only claims-based variables were used for risk adjustment, the AME (95% confidence interval) for the HF [pneumonia] cohort was -2.17 (-2.45, -1.89) [0.08 (-0.41, 0.58)] for Black Veterans and 1.32 (0.49, 2.15) [4.51 (3.65, 5.38)] for Hispanic Veterans. When clinical variables were incorporated in addition to claims-based ones, the AME, relative to White Veterans, for the HF [pneumonia] cohort was -1.57 (-1.88, -1.27) [-0.83 (-1.31, -0.36)] for Black Veterans and 1.50 (0.71, 2.30) [3.30 (2.49, 4.11)] for Hispanic Veterans. Conclusions Compared with White Veterans, Black Veterans had lower mortality, and Hispanic Veterans had higher mortality for HF and pneumonia. The inclusion of clinical variables into risk-adjustment models impacted the magnitude of racial/ethnic differences in mortality following hospitalization. Future studies examining racial/ethnic disparities should consider including clinical variables for risk adjustment.

Choosing between multiple healthcare providers requires us to simultaneously compare the expected outcomes under each provider. This comparison is complex because the composition of patients treated by each provider may differ. Similar issues arise when simultaneously comparing the adverse effects of interventions using non-randomized data. To simultaneously estimate the effects of multiple providers/interventions we propose procedures that explicitly impute the set of potential outcomes for each subject. The procedures are based on different specifications of the generalized additive models (GAM) and the Bayesian additive regression trees (BART). We compare the performance of the proposed procedures to previously proposed matching and weighting procedures using an extensive simulation study for continuous outcomes. Our simulations show that when the distributions of the covariates across treatment groups have adequate overlap, the multiple imputation procedures based on separate BART or GAM models in each treatment group are generally superior to weighting based methods and have similar and sometimes better performance than matching on the logit of the generalized propensity score. Another advantage of these multiple imputation procedures is the ability to provide point and interval estimates to a wide range of causal effect estimands. We apply the proposed procedures to comparing multiple nursing homes in Massachusetts for readmission outcomes. The proposed approach can be applied to other causal effects applications with multiple treatments.

The aim was to examine the association of patient-reported physician awareness of biological CAM use and patient perceptions of care experience and quality with a population-based study of patients with incident lung and colorectal cancer. This was a secondary data analysis using regression models. Outcomes of interest were patient reports of medical care experience and quality ratings. Among 716 patients who reported biological CAM use, 69% reported their physicians were aware of this. Patients who reported physician awareness of biological CAM use had higher adjusted scores for medical care experience ( + 5.4, 95%CI:2.3,8.6) and care quality ( + 3.6, 95%CI:−0.3, + 7.5). These associations suggest that physicians should be encouraged to inquire about biological CAM use.

Objective To determine the relationship between an advance care planning (ACP) video intervention, Pragmatic Trial of Video Education in Nursing Homes (PROVEN), and end-of-life health care transitions among long-stay nursing home residents with advanced illness. Design Pragmatic cluster randomized clinical trial. Five ACP videos were available on tablets or online at intervention facilities. PROVEN champions employed by nursing homes (usually social workers) were directed to offer residents (or their proxies) ≥1 video under certain circumstances. Control facilities employed usual ACP practices. Setting and Participants PROVEN occurred from February 2016 to May 2019 in 360 nursing homes (119 intervention, 241 control) owned by 2 health care systems. This post hoc study of PROVEN data analyzed long-stay residents ≥65 years who died during the trial who had either advanced dementia or cardiopulmonary disease (advanced illness). We required an observation time ≥90 days before death. The analytic sample included 923 and 1925 advanced illness decedents in intervention and control arms; respectively. Methods Outcomes included the proportion of residents with 1 or more hospital transfer (ie, hospitalization, emergency department use, or observation stay), multiple (≥3) hospital transfers during the last 90 days of life, and late transitions (ie, hospital transfer during the last 3 days or hospice admission on the last day of life). Results Hospital transfers in the last 90 days of life among decedents with advanced illness were significantly lower in the intervention vs control arm (proportion difference = −1.7%, 95% CI –3.2%, −0.1%). The proportion of decedents with multiple hospital transfers and late transitions did not differ between the trial arms. Conclusions and Implications Video-assisted ACP was modestly associated with reduced hospital transfers in the last 90 days of life among nursing home residents with advanced illness. The intervention was not significantly associated with late health care transitions and multiple hospital transfers.

Background Agitated and aggressive behaviors (behaviors) are common in nursing home (NH) residents with dementia. Medications commonly used to manage behaviors have dangerous side effects. NHs are adopting non-pharmacological interventions to manage behaviors, despite a lack of effectiveness evidence and an understanding of optimal implementation strategies. We are conducting an adaptive trial to evaluate the effects of personalized music on behaviors. Adaptive trials may increase efficiency and reduce costs associated with traditional RCTs by learning and making modifications to the trial while it is ongoing. Methods We are conducting two consecutive parallel cluster-randomized trials with 54 NHs in each trial (27 treatment, 27 control). Participating NHs were recruited from 4 corporations which differ in size, ownership structure, geography, and residents’ racial composition. After randomization, there were no significant differences between the NHs randomized to each trial with respect to baseline behaviors, number of eligible residents, degree of cognitive impairment, or antipsychotic use. Agitated behavior frequency is assessed via staff interviews (primary outcome), required nursing staff conducted resident assessments (secondary outcome), and direct observations of residents (secondary outcome). Between the two parallel trials, the adaptive design will be used to test alternative implementation strategies, increasingly enroll residents who are likely to benefit from the intervention, and seamlessly conduct a stage III/IV trial. Discussion This adaptive trial allows investigators to estimate the impact of a popular non-pharmaceutical intervention (personalized music) on residents’ behaviors, under pragmatic, real-world conditions testing two implementation strategies. This design has the potential to reduce the research timeline by improving the likelihood of powered results, increasingly enrolling residents most likely to benefit from intervention, sequentially assessing the effectiveness of implementation strategies in the same trial, and creating a statistical model to reduce the future need for onsite data collection. The design may also increase research equity by enrolling and tailoring the intervention to populations otherwise excluded from research. Our design will inform pragmatic testing of other interventions with limited efficacy evidence but widespread stakeholder adoption because of the real-world need for non-pharmaceutical approaches. {2a} Trial registration ClinicalTrials.govNCT03821844. Registered on January 30, 2019. This trial registration meets the World Health Organization (WHO) minimum standard.

AimsDipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycemia-mediated declines in cognitive and physical functioning compared to sulfonylureas (SUs), yet comparative studies are unavailable among older adults, especially nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents.Materials and MethodsThis new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after propensity score matching using Cox regression models.ResultsThe cohort (N=1,784) had a mean (SD) age of 80 (8) years and was 73% female. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared to SU users, DPP4I users had statistically similar 180-day rates of cognitive decline (HR=0.61, 95%CI 0.31-1.19), altered mental status events (HR=0.71, 95%CI 0.39-1.27), and functional decline (HR=0.89, 95%CI 0.51-1.56).ConclusionsRates of cognitive and functional decline were not markedly reduced among DPP4I users compared to SU users, but the point estimates and lower 95% confidence bounds do not rule out the possibility that DPP4Is result in reduced rates. Larger studies with greater statistical power should resolve this remaining uncertainty.