Faculty Bibliography

RATIONALE & OBJECTIVE:Current dietary guidelines recommend that patients with chronic kidney disease (CKD) restrict individual nutrients, such as sodium, potassium, phosphorus, and protein. This approach can be difficult for patients to implement and ignores important nutrient interactions. Dietary patterns are an alternative method to intervene on diet. Our objective was to define the associations of 4 healthy dietary patterns with risk for CKD progression and all-cause mortality among people with CKD. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:and dietary data in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURES:Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean diet (aMed), and Dietary Approaches to Stop Hypertension (DASH) diet scores were calculated from food frequency questionnaires. OUTCOMES:(1) CKD progression defined as≥50% estimated glomerular filtration rate decline, kidney transplantation, or dialysis and (2) all-cause mortality. ANALYTICAL APPROACH:Cox proportional hazards regression models adjusted for demographic, lifestyle, and clinical covariates to estimate hazard ratios (HRs) and 95% CIs. RESULTS:There were 855 cases of CKD progression and 773 deaths during a maximum of 14 years. Compared with participants with the lowest adherence, the most highly adherent tertile of Alternative Healthy Eating Index-2010, aMed, and DASH had lower adjusted risk for CKD progression, with the strongest results for aMed (HR, 0.75; 95% CI, 0.62-0.90). Compared with participants with the lowest adherence, the highest adherence tertiles for all scores had lower adjusted risk for all-cause mortality for each index (24%-31% lower risk). LIMITATIONS:Self-reported dietary intake. CONCLUSIONS:Greater adherence to several healthy dietary patterns is associated with lower risk for CKD progression and all-cause mortality among people with CKD. Guidance to adopt healthy dietary patterns can be considered as a strategy for managing CKD.

BACKGROUND:Telemedicine use rapidly increased during the COVID-19 pandemic. This study assessed quality aspects of rapid expansion of a virtual urgent care (VUC) telehealth system and the effects of a secondary telephonic screening initiative during the pandemic. METHODS:A retrospective cohort analysis was performed in a single health care network of VUC patients from March 1, 2020, through April 20, 2020. Researchers abstracted demographic data, comorbidities, VUC return visits, emergency department (ED) referrals and ED visits, dispositions, intubations, and deaths. The team also reviewed incomplete visits. For comparison, the study evaluated outcomes of non-admission dispositions from the ED: return visits with and without admission and deaths. We separately analyzed the effects of enhanced callback system targeting higher-risk patients with COVID-like illness during the last two weeks of the study period. RESULTS:A total of 18,278 unique adult patients completed 22,413 VUC visits. Separately, 718 patient-scheduled visits were incomplete; the majority were no-shows. The study found that 50.9% of all patients and 74.1% of patients aged 60 years or older had comorbidities. Of VUC visits, 6.8% had a subsequent VUC encounter within 72 hours; 1.8% had a subsequent ED visit. Of patients with enhanced follow-up, 4.3% were referred for ED evaluation. Mortality was 0.20% overall; 0.21% initially and 0.16% with enhanced follow-up (p = 0.59). Males and black patients were significantly overrepresented in decedents. CONCLUSION/CONCLUSIONS:Appropriately deployed VUC services can provide a pragmatic strategy to care for large numbers of patients. Ongoing surveillance of operational, technical, and clinical factors is critical for patient quality and safety with this modality.

BACKGROUND:Palliative care interventions in the ED capture high-risk patients at a time of crisis and can dramatically improve patient-centered outcomes. OBJECTIVE:To understand the facilitators that contributed to the success of the Primary Palliative Care for Emergency Medicine (PRIM-ER) quality improvement pilot intervention. DESIGN/METHODS:Effectiveness was evaluated through semi-structured interviews. Reach outcomes were measured by percent of all full-time emergency providers (physicians, physician assistants, nurses) who completed the intervention education components and baseline survey assessing attitudes and knowledge on end-of-life care. PARTICIPANTS/METHODS:Emergency medicine providers affiliated with two medical centers (N = 197). Interviews conducted with six key informants at both institutions. APPROACH/METHODS:Interviews were recorded, transcribed, and analyzed using deductive and inductive approaches. Descriptive statistics include reach outcomes and baseline survey results. KEY RESULTS/RESULTS:Both sites successfully implemented all components of the intervention and achieved a high level (> 75%) of intervention reach. Two themes emerged as facilitators to successful effectiveness facilitators of PRIM-ER: (1) institutional leadership support and (2) leveraging established quality improvement (QI) processes. Institutional support included leveraging leadership with authority to (a) mandate trainings; (b) substitute PRIM-ER education for normally scheduled education; and (c) provide protected time to implement intervention components. Effectiveness was also enhanced by capitalizing on existing QI processes which included (a) leveraging interdisciplinary partnerships and communication plans and (b) monitoring performance improvement data. CONCLUSIONS:Capitalizing on strong institutional leadership support and established QI processes enhanced the reach and effectiveness of the PRIM-ER pilot. These findings will guide the PRIM-ER researchers in scaling up the intervention in the remaining 33 sites, as well as enhance the planning of other complex quality improvement interventions in clinical settings. REGISTRATION DETAILS/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03424109; Grant Number: AT009844-01.

SCOPE:Serum metabolomic markers of the Dietary Approaches to Stop Hypertension (DASH) diet are previously reported. In an independent study, the similarity of urine metabolomic markers are investigated. METHODS AND RESULTS:In the DASH-Sodium trial, participants are randomly assigned to the DASH diet or control diet, and received three sodium interventions (high, intermediate, low) within each randomized diet group in random order for 30 days each. Urine samples are collected at the end of each intervention period and analyzed for 938 metabolites. Two comparisons are conducted: 1) DASH-high sodium (n = 199) versus control-high sodium (n = 193), and 2) DASH-low sodium (n = 196) versus control-high sodium. Significant metabolites identified using multivariable linear regression are compared and the top 10 influential metabolites identified using partial least-squares discriminant analysis to the results from the DASH trial. Nine out of 10 predictive metabolites of the DASH-high sodium and DASH-low sodium diets are identical. Most candidate biomarkers from the DASH trial replicated. N-methylproline, chiro-inositol, stachydrine, and theobromine replicated as influential metabolites of DASH diets. CONCLUSIONS:Candidate biomarkers of the DASH diet identified in serum replicated in urine. Replicated influential metabolites are likely to be objective biomarkers of the DASH diet.

BACKGROUND:Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences. OBJECTIVE:supplements on falls. DESIGN:2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333). SETTING:2 community-based research units. PARTICIPANTS:688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L. INTERVENTION:doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose. MEASUREMENTS:Time to first fall or death over 2 years (primary outcome). RESULTS: = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]). LIMITATIONS:per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached. CONCLUSION:doses of 1000 IU/d or higher. PRIMARY FUNDING SOURCE:National Institute on Aging.

BACKGROUND:Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. METHODS:PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be > 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims ("electronic health records," [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. DISCUSSION/CONCLUSIONS:The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings. Trial registration # NCT03407638 (February 28, 2018); CTN-0074 https://clinicaltrials.gov/ct2/show/NCT03407638?term=CTN-0074&draw=2&rank=1.

BACKGROUND:Establishment and improvement of glomerular filtration rate estimating equations requires accurate and precise laboratory measurement procedures (MPs) for filtration markers. The Advanced Research and Diagnostic Laboratory (ARDL) at the University of Minnesota, which has served as the central laboratory for the Chronic Kidney Disease Epidemiology Collaboration since 2009, has implemented several quality assurance measures to monitor the accuracy and stability of filtration marker assays over time. METHODS:To assess longitudinal stability for filtration marker assays, a 40-sample calibration panel was created using pooled serum, divided into multiple frozen aliquots stored at -80 °C. ARDL monitored 4 markers-creatinine, cystatin C, beta-2-microglobulin (B2M) and beta-trace protein-measuring 15 calibration panel aliquots from 2009 to 2019. Initial target values were established using the mean of the first 3 measurements performed in 2009-10, and differences from target were monitored over time. New MPs for cystatin C and B2M were added in 2012, with target values established using the first measurement. RESULTS:The mean percentage difference from mean target values across time was <2% for all original MPs (-0.59% for creatinine; -0.94% for cystatin C; -0.82% for B2M; 1.24% for beta-trace protein). CONCLUSIONS:Close monitoring of filtration marker trends with a calibration panel at ARDL demonstrates remarkable long-term stability of the MPs. Routine use of a calibration panel for both research studies and clinical care is recommended for filtration markers where longitudinal monitoring is important to detect analytical biases, which can mask or confound true clinical trends in patients.

OBJECTIVE:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes. METHODS:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders. RESULTS:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001). CONCLUSIONS:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Child sleep disorders are increasingly prevalent and understanding early predictors of sleep problems, starting in utero, may meaningfully guide future prevention efforts. Here, we investigated whether prenatal exposure to maternal psychological stress is associated with increased sleep problems in toddlers. We also examined whether fetal brain connectivity has direct or indirect influence on this putative association. Pregnant women underwent fetal resting-state functional connectivity MRI and completed questionnaires on stress, worry, and negative affect. At 3-year follow-up, 64 mothers reported on child sleep problems, and in the subset that have reached 5-year follow-up, actigraphy data (N = 25) has also been obtained. We observe that higher maternal prenatal stress is associated with increased toddler sleep concerns, with actigraphy sleep metrics, and with decreased fetal cerebellar-insular connectivity. Specific mediating effects were not identified for the fetal brain regions examined. The search for underlying mechanisms of the link between maternal prenatal stress and child sleep problems should be continued and extended to other brain areas.

Background/UNASSIGNED:Latino people in the US are experiencing higher excess deaths during the COVID-19 pandemic than any other racial/ethnic group, but it is unclear which subgroups within this diverse population are most affected. Such information is necessary to target policies that prevent further excess mortality and reduce inequities. Methods/UNASSIGNED:Using death certificate data for January 1, 2016 through February 29, 2020 and time-series models, we estimated the expected weekly deaths among Latino people in California from March 1 through October 3, 2020. We quantified excess mortality as observed minus expected deaths and risk ratios (RR) as the ratio of observed to expected deaths. We considered subgroups defined by age, sex, place of birth, education, occupation, and combinations of these factors. Findings/UNASSIGNED:During the first seven months of the pandemic, Latino deaths in California exceeded expected deaths by 10,316, a 31% increase. Excess death rates were greatest for individuals born in Mexico (RR 1.44; 95% PI, 1.41, 1.48) or Central America (RR 1.49; 95% PI, 1.37, 1.64), with less than a high school degree (RR 1.41; 95% PI, 1.35, 1.46), or in food-and-agriculture (RR 1.60; 95% PI, 1.48, 1.74) or manufacturing occupations (RR 1.59; 95% PI, 1.50, 1.69). Immigrant disadvantages in excess death were magnified among working-age Latinos in essential occupations. Interpretation/UNASSIGNED:The pandemic has disproportionately impacted mortality among Latino immigrants and Latinos in unprotected essential jobs; Interventions to reduce these disparities should include early vaccination, workplace safety enforcement, and expanded access to medical care. Funding/UNASSIGNED:National Institute on Aging; UCSF. RESEARCH IN CONTEXT/UNASSIGNED: