Publications

CONTEXT: Total fasting non-esterified fatty acid (NEFA) levels have been associated with mortality. The corresponding associations with NEFA levels following an oral glucose tolerance test (OGTT) and with individual fasting NEFA species are unclear.

OBJECTIVE: We evaluated the associations of post-load NEFA, fasting subclasses and individual NEFA with mortality.

DESIGN AND SETTING: The Cardiovascular Health Study is a population-based cohort study of community-dwelling adults over 64 years from four US communities that began in 1989-1990. Participants had total NEFA measured enzymatically before and two hours after an OGTT from archived serum samples collected in 1996-1997. Fasting individual NEFA were also measured using gas chromatography. Cox proportional hazard models were used to evaluate adjusted hazard ratios (aHR) for mortality associated with fasting and post-load total NEFA, and fasting individual and fatty acid subclasses (saturated, monounsaturated, n-3 and n-6 polyunsaturated, and trans).

RESULTS: The final population included 1996 participants with a mean age of 78 years. 60.5% were female. Over a median 11-year follow-up period, 1678 participants died. Total fasting NEFA was associated with higher risk of all-cause mortality (aHR per standard deviation: 1.17, 95% CI [1.10-1.23]). Total post-load NEFA was not associated with mortality. Among subclasses, only monounsaturated fatty acid (MUFA) was associated with total mortality (aHR 1.24, 95% CI [1.09-1.41]). For individual NEFAs, nervonic acid (aHR 1.06, 95% CI [1.01-1.12]), petroselaidic acid (aHR 1.21, 95% CI [1.03-1.42]) and eicosapentaenoic acid (aHR 0.90, 95% CI [0.82-0.99]) were associated with all-cause mortality.

CONCLUSION: Individual fasting NEFAs represent attractive candidates for medical and public health interventions aimed at improving survivorship in older adults and should be investigated further.

BACKGROUND: Inpatient hyperglycemia is common among adults, and management varies.

PURPOSE: To systematically identify guidelines on inpatient hyperglycemia management.

DATA SOURCES: MEDLINE, Guidelines International Network, and specialty society websites were searched from 1 January 2010 to 14 August 2024.

STUDY SELECTION: Clinical practice guidelines pertaining to blood glucose management in hospitalized adults were included.

DATA EXTRACTION: Two authors screened articles and extracted data, and three assessed guideline quality. Recommendations on inpatient monitoring, treatment targets, medications, and care transitions were collected.

DATA SYNTHESIS: Guidelines from 10 organizations met inclusion criteria, and 5 were assessed to be of high quality per the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) instrument. All guidelines recommended monitoring blood glucose for patients with diabetes and nine for admission hyperglycemia. Eight guidelines recommended an upper blood glucose target of 180 mg/dL, five with a lower limit of 100 mg/dL and three of 140 mg/dL. Guidelines were in agreement on using capillary blood glucose monitoring, and three guidelines included discussion of continuous monitoring. Hyperglycemia treatment with basal-bolus insulin alone (n = 3) or with correction (n = 5) was most commonly recommended, while sliding scale insulin was advised against (n = 5). Guidance on use of oral diabetes medications was inconsistent. Five guidelines included discussion of transitioning to home medications. Recommendations for hypoglycemia management and diabetes management in older adults were largely limited to outpatient guidance.

LIMITATIONS: Non-English-language guidelines were excluded.

CONCLUSIONS: While there is consensus on inpatient blood glucose monitoring and use of basal-bolus insulin, there is disagreement on treatment targets and use of home medications and little guidance on how to transition treatment at discharge.

BACKGROUND: There is a growing interest in CMR radiomic signatures as novel imaging biomarkers of cardiac disease. However, very little is known about pathological correlates of the radiomics signature of myocardium on CMR sequences.

PURPOSE: To investigate the association between CMR myocardial radiomic signatures and histological features in patients with non-ischemic dilated cardiomyopathy (DCM).

MATERIALS AND METHODS: CMR images from DCM patients who underwent CMR followed by endomyocardial biopsy within 6 [2-15] days were used to investigate the association between myocardial radiomic signatures measured from native T1, extra-cellular volume (ECV), late gadolinium enhancement (LGE) and histological features. Radiomic first-order and textural features were computed for each sequence from the mid-septal myocardium near the biopsy region. Hierarchical clustering was then applied to identify distinct radiomic clusters. A representative feature known as the "medoid" was identified within each cluster based on its minimal dissimilarity from other features. Logistic regression models were built using one medoid per model to evaluate the association between each medoid and histological feature. Association was determined using odds ratio (OR) with a 95% confidence interval.

RESULTS: 132 DCM patients (71% male; 54±15 years) were included in the study. Clustering analysis unveiled two radiomic clusters for each sequence. For native T1, the medoids were textural features. The first medoid was associated with fibrosis, inflammation, myocyte hypertrophy, vacuolization, and fat replacement (OR=2.84[1.62-5.46]; OR=2.05[1.15-4.03]; OR=2.39[1.01-6.62]; OR=2.03[1.22-3.60]; OR=0.35[0.12-0.86]; respectively). The second medoid was associated with nuclear generation (OR=0.55[0.31-0.91]). ECV medoids included first-order and textural features. The first-order medoid was associated with fibrosis (OR=2.97[1.75-5.46]), myocyte hypertrophy (OR=3.20[1.17-10.37]), and nuclear degeneration (OR=1.66[1.02-2.89]), while medoid 2 (texture) was associated with fibrosis (OR=4.44[2.26-10.00]). LGE medoid 1 (texture) was associated with myocyte hypertrophy (OR=0.31[0.10-0.77]), while medoid 2 (texture) was associated with fibrosis (OR=2.40[1.38-4.66]) and vacuolization (OR=2.00[1.16-3.72]).

CONCLUSIONS: In DCM patients, CMR radiomic signatures were associated with myocardial tissue composition, as assessed by invasive biopsy.

IMPORTANCE: The 2014 Improving Medicare Post-Acute Care Transformation (IMPACT) Act aimed to improve postacute care quality and outcomes. This study examines changes in delirium, a key quality indicator, over 5 years following its implementation.

OBJECTIVE: To compare the persistence and resolution of delirium within skilled nursing facilities (SNFs) between 2014 and 2019.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included SNF admissions from a 5% Medicare random sample, with delirium assessments conducted between January 1 and December 31 in 2014 and 2019. The analysis of persistent delirium consisted of patients with delirium at SNF admission and a subsequent delirium assessment during their SNF stay. Analyses were conducted from December 2023 to October 2024.

EXPOSURES: Year 2019 compared with year 2014.

MAIN OUTCOMES AND MEASURES: Delirium was measured using the Minimum Data Set (MDS) Confusion Assessment Method at SNF admission and at a subsequent assessment within 30 days of admission. Multinomial logistic regression was used to compare the rates of resolved delirium, persistent delirium, and death between 2014 and 2019 after adjusting for patient characteristics and SNF care factors.

RESULTS: The sample included a total of 432 037 SNF admissions before exclusions and 306 998 after exclusions. For SNF admissions in 2014, 6933 of 162 161 patients (4.3%) had delirium at admission, compared with 3595 of 144 837 patients (2.5%) in 2019. In 2014, there were 6096 patients (mean [SD] age, 80.6 [11.0] years; 3565 women [58.5%]), and in 2019, there were 2778 patients (mean [SD] age, 80.2 [10.7] years; 1546 women [55.7%]) with delirium and follow-up assessments. The adjusted prevalence of persistent delirium decreased from 3347 of 6096 patients (62.3%; 95% CI, 60.2%-64.4%) in 2014 to 1316 of 2778 patients (54.7%; 95% CI, 52.0%-57.4%) in 2019, whereas delirium resolution increased from 1734 of 6096 patients (29.1%; 95% CI, 27.1%-31.1%) in 2014 to 1010 of 2778 patients (37.4%; 95% CI, 34.7%-40.0%) in 2019.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found a reduction in the prevalence of delirium at SNF admission and an improvement in delirium resolution during the stay in the 5 years following the IMPACT Act. However, the high prevalence of persistent delirium warrants further efforts to improve delirium management in SNF.

The emerging paradigm of whole person health shares many core principles with traditional complementary and integrative health frameworks, including Tai Chi and qigong (TCQ). In the Fall of 2023, the Harvard Medical School Osher Center for Integrative Health hosted the inaugural international conference on The Science of Tai Chi for Whole Person Health: Advancing the Integration of Mind-Body Practices into Contemporary Health Care held at Harvard Medical School. A two-part white paper was written to summarize key conference topics, findings, and issues. Part I presented here summarizes the rationale for the conference and synthesizes the state of evidence for TCQ as rehabilitative and preventive tools for a range of clinical conditions, including falls and balance, cognition, mental health, sleep, cardiorespiratory health, musculoskeletal health, cancer, as well as translational evidence related to the neurophysiology, brain and immune function, and biomarkers of inflammation. The state of science of TCQ, viewed through the lens of traditional East Asian health constructs, is also discussed. Part II of this white paper outlines evidence gaps and opportunities and discusses strategies to address challenges in TCQ research, dissemination, and implementation.

BACKGROUND: Oncology providers often lack the confidence to make clinical recommendations about medical cannabis (MC). This study aimed to develop and evaluate the feasibility of implementing an educational curriculum on the use of MC in patient care for oncology trainees.

METHODS: A multidisciplinary team designed an educational curriculum for MC use in oncology. The curriculum was piloted as a 1-hour interactive webinar across 8 United States-based hematology/oncology fellowship programs between 2022 and 2023. Incentivized surveys measuring feasibility outcomes, including cultural attitudes/norms, acceptability, compatibility, and self-efficacy (a composite index of self-confidence in discussing MC efficacy, risks, modes of use, and role in symptom management), were distributed before, immediately after, and 12 weeks post-webinar.

RESULTS: Of 103 trainees, 75 (72.8%) completed the pretraining survey and 66 (64.1%) completed the posttraining survey. Most respondents believed discussions about the role of MC in symptom management were valuable (n=56; 74.7%), though few (14.7%) believed trainees were expected to engage in such discussions. Most participants rated the curriculum as helpful (92.4%), beneficial for oncology trainees (84.8%), and likely to be recommended to colleagues (87.9%). Post-webinar, 78.8% of participants reported an increased likelihood of initiating discussions with patients regarding MC. There were significant improvements in the composite self-confidence index from pre- to post-webinar (2.7% vs 65.2%; P<.001), which persisted in the follow-up surveys (n=36; response rate, 34.9%).

CONCLUSIONS: This multisite study demonstrates the feasibility of implementing a novel curriculum focused on MC for oncology trainees. These findings can guide the design of a prospective, multi-institutional study to evaluate knowledge expansion, retention, and behavioral changes resulting from the intervention.

BACKGROUND: In the United States, the landscape of unpaid care delivery is both challenging and complex, with millions of individuals undertaking the vital role of helping families (broadly defined) manage their health care and well-being. This includes 48 million caregivers of adults, 42 million of whom are caregivers of adults aged 50 years or older. These family care partners provide critical and often daily support for tasks such as dressing and bathing, as well as managing medications, medical equipment, appointments, and follow-up care plans.

OBJECTIVE: This study aimed to implement a novel patient portal-based intervention to identify, engage, and support care partners in clinical settings.

METHODS: The project team collaborated with 3 health care organizations (6 primary care practices in total) to design and implement a patient portal-based intervention. Three days in advance of a visit, patients were invited to log on to their patient portal account and answer a brief questionnaire as part of the routine electronic check-in process asking them to (1) identify themselves as the patient or someone answering for the patient, (2) report major life changes, (3) set the agenda for the upcoming visit, and (4) report on care partner responsibilities. Respondents' answers to this brief questionnaire were available to providers ahead of the visit. Patients with care partner responsibilities, as well as care partners answering the questionnaire on behalf of patients, were provided a link to the ARCHANGELS Caregiver Intensity Index to measure the intensity of their caregiving role and motivate care partners to connect with suggested state and local resources.

RESULTS: The intervention was launched in September 2022 at Organization A. Organization B launched in May 2023 in one clinic and June 2023 in the other. In focus groups, staff and clinicians reported that the intervention was easy to implement and did not cause workflow disruption. At 6 months post implementation, across both organizations, a total of 22,152 patients had received questionnaires and 13,825 (62.4%) had submitted completed questionnaires. Full data will be reported at the completion of the intervention period.

CONCLUSIONS: Early results suggest that the intervention could be an easily scalable and adaptable method of identifying and supporting care partners in clinical settings.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/66708.

BACKGROUND: Many hospitals have created the position of equity officer (EQO) in efforts to reduce disparities and address social determinants of health.

OBJECTIVE: To describe EQOs' experiences and needs, and the environment in which they operate.

DESIGN AND PARTICIPANTS: A national, cross-sectional survey of EQOs in US community hospitals in 2023. Hospitals determined not to have an EQO were excluded, leaving an estimated 1228 eligible EQOs.

MAIN MEASURES: Characteristics of the respondents and their positions, perceptions of preparedness, critical attributes for success, and obstacles.

KEY RESULTS: We obtained 363 survey responses (response rate 29.6%). About one-third of respondents had been in their position for less than 1 year (35.8%), and 46.1% reported directly to the CEO. Only 8.3% had their entire full-time equivalent effort dedicated to equity work. Respondents scored positively on about half of the criteria considered important for a robust equity environment. Only 14.4% reported their hospital had an adequate, dedicated equity budget. Persons of color were significantly more likely to work in places where equity was included in the strategic plan, but also faced more environment-related obstacles. Overall, many EQOs felt less than well prepared to fulfill certain key functions of their position, such as developing community health programs (47.2%) or changing the culture of their hospital (46.9%). More than 90% of respondents identified good community relations (93.7%) and access to their hospital or health system's equity data (92.2%) as critically or very important attributes of their position. The most common obstacle to achieving their equity goals was lack of sufficient equity staff (81.5%). Differences by hospital type also were noted.

CONCLUSIONS: The position of EQO is relatively new and the majority in these positions commit only a small amount of their effort to health equity issues. EQOs will need appropriate and adequate resources going forward to achieve their goals.

BACKGROUND: The long-term associations between metal mixtures in pregnancy and women's mid-life blood pressure (BP) and hypertension remain unclear.

METHODS: In Project Viva (enrolled 1999-2002), we measured nonessential (arsenic, barium, cadmium, cesium, mercury, lead) and essential metals (copper, magnesium, manganese, selenium, zinc) in red blood cells, along with folate and vitamin B12 in plasma, collected during pregnancy. We measured mid-life BP from 2017 to 2021 (median age, 51.2 years). We examined associations of individual metals with BP using linear regression and with hypertension (≥130/80 mm Hg or use of antihypertensive medication) using modified Poisson regression. We used Bayesian kernel machine regression to examine the mixture effects of metals and micronutrients.

RESULTS: The median follow-up time of the 493 women was 18.1 years (interquartile range, 17.8-18.6 years). After adjustment, a doubling of copper and manganese was associated with 0.75 (95% CI, 0.57-0.99) and 0.80 (95% CI, 0.71-0.91) times the risk of hypertension, respectively. Although higher cesium and selenium levels were associated with a slightly increased risk of hypertension, the 95% CIs were wide and crossed the null. A doubling of vitamin B12 was associated with a 3.64 (95% CI, 1.23-6.04) mm Hg lower systolic BP and a 2.52 (95% CI, 0.72-4.32) mm Hg lower diastolic BP. Bayesian kernel machine regression showed linear associations with no metal-metal or metal-micronutrient interactions. The essential metal mixture was monotonically associated with lower BP, while its association with hypertension showed threshold effects.

CONCLUSIONS: Optimizing essential metal levels during pregnancy, particularly copper and manganese, along with vitamin B12, may protect against higher BP and hypertension in mid-life women.