Publications

OBJECTIVE: To determine the effects of intensive blood pressure treatment on orthostatic hypertension.

DESIGN: Systematic review and individual participant data meta-analysis.

DATA SOURCES: MEDLINE, Embase, and Cochrane CENTRAL databases through 13 November 2023.

INCLUSION CRITERIA: Population: ≥500 adults, age ≥18 years with hypertension or elevated blood pressure; intervention: randomized trials of more intensive antihypertensive drug treatment (lower blood pressure goal or active agent) with duration ≥6 months; control: less intensive antihypertensive drug treatment (higher blood pressure goal or placebo); outcome: measured standing blood pressure.

MAIN OUTCOMES: Orthostatic hypertension, defined as an increase in systolic blood pressure ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg after changing from sitting to standing.

DATA SYNTHESIS: Two investigators independently abstracted articles. Individual participant data from nine trials identified during the systematic review were appended together as a single dataset.

RESULTS: Of 31 124 participants with 315 497 standing blood pressure assessments, 9% had orthostatic hypotension (that is, a drop in blood pressure after standing of systolic ≥20 mm Hg or diastolic ≥10 mm Hg), 17% had orthostatic hypertension, and 3.2% had both a rise in systolic blood pressure and standing blood pressure ≥140 mm Hg at baseline. The effects of more intensive treatment were similar across trials with odds ratios for orthostatic hypertension ranging from 0.85 to 1.08 (I2=38.0%). During follow-up, 17% of patients assigned to more intensive treatment had orthostatic hypertension, whereas 19% of those assigned less intensive treatment had orthostatic hypertension. Compared with less intensive treatment, the risk of orthostatic hypertension was lower with more intensive blood pressure treatment (odds ratio 0.93, 95% confidence interval 0.90 to 0.96). Effects were greater among non-black versus black adults (odds ratio 0.86 v 0.97; P for interaction=0.003) and adults without diabetes versus those with diabetes (0.88 v 0.96; P for interaction=0.05) but did not differ by age ≥75 years, sex, baseline seated blood pressure ≥130/≥80 mm Hg, obesity, stage 3 kidney disease, stroke, cardiovascular disease, standing systolic blood pressure ≥140 mm Hg, or pre-randomization orthostatic hypertension (P for interactions ≥0.05).

CONCLUSIONS: In this pooled cohort of adults with elevated blood pressure or hypertension, orthostatic hypertension was common and more intensive blood pressure treatment modestly reduced the occurrence of orthostatic hypertension. These findings suggest that approaches generally used for seated hypertension may also prevent hypertension on standing.

STUDY REGISTRATION: Prospero CRD42020153753 (original proposal).

BACKGROUND: To ensure that health services are high-quality, trusted and used by the population, their design and improvement should start from the perspective of what matters to people. Patient journey mapping (PJM) is one research method that centers the experiences of individuals living with health conditions and follows their pathways through care and recovery. This paper describes a novel, qualitative PJM methodology used in Vietnam and the Philippines to inform the co-design of a people-centered viral hepatitis screening, care and treatment pathway for individuals living with chronic hepatitis, which is a significant public health concern in the Asia-Pacific region.

METHODS: Data collection involved in-depth interviews with a purposive sample of 63 people living with hepatitis (demand-side) and focus group discussions with healthcare providers working in the same geographical areas (supply-side). Rapid deductive qualitative analysis was used to identify typical journeys, and related barriers and enablers. The methodology was implemented over 8 weeks, adapting the Consolidated Criteria for Reporting Qualitative Research (COREQ).

RESULTS: This paper demonstrates how a PJM methodology that incorporates patient and HCP perspectives can be feasibly implemented in two LMIC contexts, while fulfilling many of the criteria identified by the COREQ guidelines. Sharing such methods and associated instruments may help to enable broader uptake and application in other LMIC settings, providing health systems practitioners with a critical tool to identify and overcome barriers in and promote the delivery of people-centered health services globally.

CONCLUSION: Despite limited uptake, especially in resource-limited contexts and at the primary healthcare level, PJM is a novel research method with the potential to make promising contributions to people-centered health service design.

PURPOSE: To inform decision making around mammography-screening frequency and cessation, we previously used Fine-Gray competing-risk regression to develop and validate a model to estimate older women's 10-year risk of breast cancer and their competing risk of non-breast cancer (non-BC) death. Here, we aimed to understand the amount of incident breast cancer and non-BC death risk explained by our model among women ≥ 65y.

METHODS: We included women ≥ 65y who completed the 2004 Nurses' Health Study questionnaire (NHS, n = 59,662) or who participated in the Women's Health Initiative-Extension Study (WHI-ES, n = 82,528). We calculated our model's full and risk factor-specific population attributable risk (PAR%) for incident breast cancer and non-BC death.

RESULTS: Mean age of the NHS participants was 73.5y (SD 5.2); 3.1% were diagnosed with breast cancer and 26.1% experienced non-BC death within 10 years. Mean age of WHI-ES participants was 73.6y (SD 5.4); 4.2% were diagnosed with breast cancer and 17.7% experienced non-BC death within 10 years. The full-model PAR% for breast cancer was 58.8% (22.7-80.6) in NHS and 54.8% (24.8-75.2%) in WHI-ES. Modifiable risk factors explained approximately 1/3 of breast cancer risk; BMI ≥ 30 had a PAR% of 6.5% (3.1-9.9%) in NHS and 12.2% (8.5-16.0%) in WHI-ES. For non-BC death, the full-model PAR% was 94.2% (91.4-96.1%) in NHS and 86.2% (80.9-90.0%) in WHI-ES.

CONCLUSIONS: Our competing-risk model explained the majority of breast cancers and non-BC deaths in women ≥ 65y, and we identified risk factors (e.g., elevated BMI) that may be targeted to reduce the burden of breast cancer in older women.

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: 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.

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.

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.