Publications by authors named "Long H Ngo"

91 Publications

Comparative Implementation of a Brief App-Directed Protocol for Delirium Identification by Hospitalists, Nurses, and Nursing Assistants : A Cohort Study.

Ann Intern Med 2021 Nov 9. Epub 2021 Nov 9.

Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts (L.H.N.).

Background: Systematic screening improves delirium identification among hospitalized older adults. Little data exist on how to implement such screening.

Objective: To test implementation of a brief app-directed protocol for delirium identification by physicians, nurses, and certified nursing assistants (CNAs) in real-world practice relative to a research reference standard delirium assessment (RSDA).

Design: Prospective cohort study.

Setting: Large urban academic medical center and small rural community hospital.

Participants: 527 general medicine inpatients (mean age, 80 years; 35% with preexisting dementia) and 399 clinicians (53 hospitalists, 236 nurses, and 110 CNAs).

Measurements: On 2 study days, enrolled patients had an RSDA. Subsequently, CNAs performed an ultra-brief 2-item screen (UB-2) for delirium, whereas physicians and nurses performed a 2-step protocol consisting of the UB-2 followed in those with a positive screen result by the 3-Minute Diagnostic Assessment for the Confusion Assessment Method.

Results: Delirium was diagnosed in 154 of 924 RSDAs (17%) and in 114 of 527 patients (22%). The completion rate for clinician protocols exceeded 97%. The CNAs administered the UB-2 in a mean of 62 seconds (SD, 51). The 2-step protocols were administered in means of 104 seconds (SD, 99) by nurses and 106 seconds (SD, 105) by physicians. The UB-2 had sensitivities of 88% (95% CI, 72% to 96%), 87% (CI, 73% to 95%), and 82% (CI, 65% to 91%) when administered by CNAs, nurses, and physicians, respectively, with specificities of 64% to 70%. The 2-step protocol had overall accuracy of 89% (CI, 83% to 93%) and 87% (CI, 81% to 91%), with sensitivities of 65% (CI, 48% to 79%) and 63% (CI, 46% to 77%) and specificities of 93% (CI, 88% to 96%) and 91% (CI, 86% to 95%), for nurses and physicians, respectively. Two-step protocol sensitivity for moderate to severe delirium was 78% (CI, 54% to 91%).

Limitation: Two sites; limited diversity.

Conclusion: An app-directed protocol for delirium identification was feasible, brief, and accurate, and CNAs and nurses performed as well as hospitalists.

Primary Funding Source: National Institute on Aging.
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http://dx.doi.org/10.7326/M21-1687DOI Listing
November 2021

Filling a gap in safety metrics: development of a patient-centred framework to identify and categorise patient-reported breakdowns related to the diagnostic process in ambulatory care.

BMJ Qual Saf 2021 Oct 16. Epub 2021 Oct 16.

Department of Medicine, University of Texas McGovern Medical School, Houston, Texas, USA.

Background: Patients and families are important contributors to the diagnostic team, but their perspectives are not reflected in current diagnostic measures. Patients/families can identify some breakdowns in the diagnostic process beyond the clinician's view. We aimed to develop a framework with patients/families to help organisations identify and categorise patient-reported diagnostic process-related breakdowns (PRDBs) to inform organisational learning.

Method: A multi-stakeholder advisory group including patients, families, clinicians, and experts in diagnostic error, patient engagement and safety, and user-centred design, co-developed a framework for PRDBs in ambulatory care. We tested the framework using standard qualitative analysis methods with two physicians and one patient coder, analysing 2165 patient-reported ambulatory errors in two large surveys representing 25 425 US respondents. We tested intercoder reliability of breakdown categorisation using the Gwet's AC1 and Cohen's kappa statistic. We considered agreement coefficients 0.61-0.8=good agreement and 0.81-1.00=excellent agreement.

Results: The framework describes 7 patient-reported breakdown categories (with 40 subcategories), 19 patient-identified contributing factors and 11 potential patient-reported impacts. Patients identified breakdowns in each step of the diagnostic process, including missing or inaccurate main concerns and symptoms; missing/outdated test results; and communication breakdowns such as not feeling heard or misalignment between patient and provider about symptoms, events, or their significance. The frequency of PRDBs was 6.4% in one dataset and 6.9% in the other. Intercoder reliability showed good-to-excellent reliability in each dataset: AC1 0.89 (95% CI 0.89 to 0.90) to 0.96 (95% CI 0.95 to 0.97); kappa 0.64 (95% CI 0.62, to 0.66) to 0.85 (95% CI 0.83 to 0.88).

Conclusions: The PRDB framework, developed in partnership with patients/families, can help organisations identify and reliably categorise PRDBs, including some that are invisible to clinicians; guide interventions to engage patients and families as diagnostic partners; and inform whole organisational learning.
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http://dx.doi.org/10.1136/bmjqs-2021-013672DOI Listing
October 2021

Psychophysiologic symptom relief therapy for chronic back pain: a pilot randomized controlled trial.

Pain Rep 2021 Sep-Oct;6(3):e959. Epub 2021 Sep 23.

Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Introduction: Chronic back pain is the leading cause of disability in the United States. Based on the hypothesis that nonspecific back pain may be rooted in a psychophysiologic etiology, we propose a new approach to chronic back pain.

Objectives: A pilot study was conducted to assess whether psychophysiologic symptom relief therapy (PSRT) can reduce disability and back pain bothersomeness for patients with chronic back pain.

Methods: This was a three-armed, randomized trial for adults with nonspecific chronic back pain that compared PSRT with usual care and an active comparator (mindfulness-based stress reduction [MBSR]). Psychophysiologic symptom relief therapy-randomized participants received a 12-week (36 hours) course based on the psychophysiological model of pain. All groups were administered validated questionnaires at baseline and at 4, 8, 13, and 26 weeks. The primary outcome was the reduction in pain disability measured by the Roland-Morris Disability Questionnaire.

Results: The mean Roland-Morris Disability Questionnaire score for the PSRT group (n = 11) decreased from 9.5 (±4.3 SDs) to 3.3 (±5.1) after 26 weeks which was statistically significant compared with both MBSR (n = 12) ( = 0.04) and usual care (n = 12) ( = 0.03). Pain bothersomeness scores and pain-related anxiety decreased significantly over 26 weeks in PSRT compared with MBSR and usual care (data in manuscript). At 26 weeks, 63.6% of the PSRT arm reported being pain free (0/10 pain) compared with 25.0% and 16.7% in MBSR and usual care arms, respectively. Psychophysiologic symptom relief therapy attendance was 76%, and there was 100% follow-up of all groups.

Conclusion: Psychophysiologic symptom relief therapy is a feasible and potentially highly beneficial treatment for patients with nonspecific back pain.
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http://dx.doi.org/10.1097/PR9.0000000000000959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476063PMC
September 2021

Noncontrast Cardiac Magnetic Resonance Imaging Predictors of Heart Failure Hospitalization in Heart Failure With Preserved Ejection Fraction.

J Magn Reson Imaging 2021 Sep 24. Epub 2021 Sep 24.

Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.

Background: Heart failure patients with preserved ejection fraction (HFpEF) are at increased risk of future hospitalization. Contrast agents are often contra-indicated in HFpEF patients due to the high prevalence of concomitant kidney disease. Therefore, the prognostic value of a noncontrast cardiac magnetic resonance imaging (MRI) for HF-hospitalization is important.

Purpose: To develop and test an explainable machine learning (ML) model to investigate incremental value of noncontrast cardiac MRI for predicting HF-hospitalization.

Study Type: Retrospective.

Population: A total of 203 HFpEF patients (mean, 64 ± 12 years, 48% women) referred for cardiac MRI were randomly split into training validation (143 patients, ~70%) and test sets (60 patients, ~30%).

Field Strength: A 1.5 T, balanced steady-state free precession (bSSFP) sequence.

Assessment: Two ML models were built based on the tree boosting technique and the eXtreme Gradient Boosting model (XGBoost): 1) basic clinical ML model using clinical and echocardiographic data and 2) cardiac MRI-based ML model that included noncontrast cardiac MRI markers in addition to the basic model. The primary end point was defined as HF-hospitalization.

Statistical Tests: ML tool was used for advanced statistics, and the Elastic Net method for feature selection. Area under the receiver operating characteristic (ROC) curve (AUC) was compared between models using DeLong's test. To gain insight into the ML model, the SHapley Additive exPlanations (SHAP) method was leveraged. A P-value <0.05 was considered statistically significant.

Results: During follow-up (mean, 50 ± 39 months), 85 patients (42%) reached the end point. The cardiac MRI-based ML model using the XGBoost algorithm provided a significantly superior prediction of HF-hospitalization (AUC: 0.81) compared to the basic model (AUC: 0.64). The SHAP analysis revealed left atrium (LA) and right atrium (RV) strains as top imaging markers contributing to its performance with cutoff values of 17.5% and -15%, respectively.

Data Conclusions: Using an ML model, RV and LA strains measured in noncontrast cardiac MRI provide incremental value in predicting future hospitalization in HFpEF.

Evidence Level: 3 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27932DOI Listing
September 2021

A mobile app for delirium screening.

JAMIA Open 2021 Apr 20;4(2):ooab027. Epub 2021 May 20.

Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Objective: The objective of this study is to describe the algorithm and technical implementation of a mobile app that uses adaptive testing to assess an efficient mobile app for the diagnosis of delirium.

Materials And Methods: The app was used as part of a NIH-funded project to assess the feasibility, effectiveness, administration time, and costs of the 2-step delirium identification protocol when performed by physicians and nurses, and certified nursing assistants (CNA). The cohort included 535 hospitalized patients aged 79.7 (SD = 6.6) years enrolled at 2 different sites. Each patient was assessed on 2 consecutive days by the research associate who performed the reference delirium assessment. Thereafter, physicians, nurses, and CNAs performed adaptive delirium assessments using the app. Qualitative data to assess the experience of administering the 2-step protocol, and the app usability were also collected and analyzed from 50 physicians, 189 nurses, and 83 CNAs. We used extensible hypertext markup language (XHTML) and JavaScript to develop the app for the iOS-based iPad. The App was linked to Research Electronic Data Capture (REDCap), a relational database system, via a REDCap application programming interface (API) that sent and received data from/to the app. The data from REDCap were sent to the Statistical Analysis System for statistical analysis.

Results: The app graphical interface was successfully implemented by XHTML and JavaScript. The API facilitated the instant updating and retrieval of delirium status data between REDCap and the app. Clinicians performed 881 delirium assessments using the app for 535 patients. The transmission of data between the app and the REDCap system showed no errors. Qualitative data indicated that the users were enthusiastic about using the app with no negative comments, 82% positive comments, and 18% suggestions of improvement. Delirium administration time for the 2-step protocol showed similar total time between nurses and physicians (103.9 vs 106.5 seconds). Weekly enrollment reports of the app data were generated for study tracking purposes, and the data are being used for statistical analyses for publications.

Discussion: The app developed using iOS could be easily converted to other operating systems such as Android and could be linked to other relational databases beside REDCap, such as electronic health records to facilitate better data retrieval and updating of patient's delirium status.

Conclusion: Our app operationalizes an adaptive 2-step delirium screening protocol. Its algorithm and cross-plat formed code of XHTML and JavaScript can be easily exported to other operating systems and hardware platforms, thus enabling wider use of the efficient delirium screening protocol that we have developed. The app is currently implemented as a research tool, but with adaptation could be implemented in the clinical setting to facilitate widespread delirium screening in hospitalized older adults.
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http://dx.doi.org/10.1093/jamiaopen/ooab027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446432PMC
April 2021

Risk factors for opioid-related adverse drug events among older adults after hospital discharge.

J Am Geriatr Soc 2021 Sep 15. Epub 2021 Sep 15.

Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Background: Although opioids are initiated on hospital discharge in millions of older adults each year, there are no studies examining patient- and prescribing-related risk factors for opioid-related adverse drug events (ADEs) after hospital discharge among medical patients.

Methods: A retrospective cohort study of a national sample of Medicare beneficiaries aged 65 years and older, hospitalized for a medical reason, with at least one claim for an opioid within 2 days of hospital discharge. We excluded patients receiving hospice care and patients admitted from or discharged to a facility. We used administrative billing codes and medication claims to define potential opioid-related ADEs within 30 days of hospital discharge, and competing risks regression to identify risk factors for these events.

Results: Among 22,879 medical hospitalizations (median age 74, 36.9% female) with an opioid claim within 2 days of hospital discharge, a potential opioid-related ADE occurred in 1604 (7.0%). Independent risk factors included age of 80 years and older (HR 1.18, 95% CI 1.05-1.33); clinical conditions, including kidney disease (HR 1.22, 95% CI 1.08-1.37), dementia/delirium (HR 1.38, 95% CI 1.22-1.56), anxiety disorder (HR 1.20, 95% CI 1.06-1.36), opioid use disorder (HR 1.20, 95% CI 1.03-1.39), intestinal disorders (HR 1.31, 95% CI 1.15-1.49), pancreaticobiliary disorders (HR 1.32, 95% CI 1.09-1.61), and musculoskeletal and nervous system injuries (HR 1.35, 95% CI 1.17-1.54); red flags for opioid misuse (HR 1.37, 95% CI 1.04-1.80); opioid use in the 30 days before hospitalization (HR 1.20, 95% CI 1.08-1.34); and prescription of long-acting opioids (HR 1.34, 95% CI 1.06-1.70).

Conclusions: Potential opioid-related ADEs occurred within 30 days of hospital discharge in 7.0% of older adults discharged from a medical hospitalization with an opioid prescription. Identified risk factors can be used to inform physician decision-making, conversations with older adults about risk, and development and targeting of harm reduction strategies.
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http://dx.doi.org/10.1111/jgs.17453DOI Listing
September 2021

Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study.

J Neuroinflammation 2021 Apr 30;18(1):103. Epub 2021 Apr 30.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation.

Methods: We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids.

Results: Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline.

Conclusions: In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.
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http://dx.doi.org/10.1186/s12974-021-02145-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088047PMC
April 2021

Sensitivity of Myocardial Radiomic Features to Imaging Parameters in Cardiac MR Imaging.

J Magn Reson Imaging 2021 09 1;54(3):787-794. Epub 2021 Mar 1.

Department of Medicine (Cardiovascular Division), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.

Background: Cardiac magnetic resonance (MR) images are often collected with different imaging parameters, which may impact the calculated values of myocardial radiomic features.

Purpose: To investigate the sensitivity of myocardial radiomic features to changes in imaging parameters in cardiac MR images.

Study Type: Prospective.

Population: A total of 11 healthy participants/five patients.

Field Strength/ Sequence: A 3 T/cine balanced steady-state free-precession, T -weighted spoiled gradient-echo, T -weighted turbo spin-echo, and quantitative T and T mapping. For each sequence, the flip angle, in-plane resolution, slice thickness, and parallel imaging technique were varied to study the sensitivity of radiomic features to alterations in imaging parameters.

Assessment: Myocardial contours were manually delineated by experienced readers, and a total of 1023 radiomic features were extracted using PyRadiomics with 11 image filters and six feature families.

Statistical Tests: Sensitivity was defined as the standardized mean difference (D effect size), and the robust features were defined at sensitivity < 0.2. Sensitivity analysis was performed on predefined sets of reproducible features. The analysis was performed using the entire cohort of 16 subejcts.

Results: 64% of radiomic features were robust (sensitivity < 0.2) to changes in any imaging parameter. In qualitative sequences, radiomic features were most sensitive to changes in in-plane spatial resolution (spatial resolution: 0.6 vs. flip angle: 0.19, parallel imaging: 0.18, slice thickness: 0.07; P < 0.01 for all); in quantitative sequences, radiomic features were least sensitive to changes in spatial resolution (spatial resolution: 0.07 vs. slice thickness: 0.16, flip angle: 0.24; P < 0.01 for all). In an individual feature level, no singular feature family/image filter was identified as robust (sensitivity < 0.2) across sequences; however, highly sensitive features were predominantly associated with high-frequency wavelet filters across all sequences (32/50 features).

Data Conclusion: In cardiac MR, a considerable number of radiomic features are sensitive to changes in sequence parameters.

Evidence Level: 1 TECHNICAL EFFICACY: Stage 1.
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http://dx.doi.org/10.1002/jmri.27581DOI Listing
September 2021

Trends of Ruptured and Unruptured Aneurysms Treatment in the United States in Post-ISAT Era: A National Inpatient Sample Analysis.

J Am Heart Assoc 2021 02 9;10(4):e016998. Epub 2021 Feb 9.

Neurosurgery Service Beth Israel Deaconess Medical CenterHarvard Medical School Boston MA.

Background The ISAT (International Subarachnoid Aneurysm Trial) has generated a paradigm shift towards endovascular treatment for intracranial aneurysms but remains unclear if this has led to a true reduction in the risk for aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between the treatment burden of unruptured and ruptured aneurysms in the post-ISAT era. Methods and Results Admissions data from the National Inpatient Sample (2004-2014) were extracted, including patients with a primary diagnosis of aSAH or unruptured intracranial aneurysms treated by clipping or coiling. Within each year, this combined group was randomly matched to non-aneurysmal control group, based on age, sex, and Elixhauser comorbidity index. Multinomial regression was performed to calculate the relative risk ratio of undergoing treatment for either ruptured or unruptured aneurysms in comparison with the reference control group, adjusted for time. After adjusting for National Inpatient Sample sampling effects, 243 754 patients with aneurysm were identified, 174 580 (71.6%) were women; mean age, 55.4±13.2 years. A total of 121 882 (50.01%) patients were treated for unruptured aneurysms, 79 627 (65.3%) endovascularly and 42 256 (34.7%) surgically. A total of 121 872 (49.99%) patients underwent procedures for aSAH, 68 921 (56.6%) endovascular, and 52 951 (43.5%) surgically. Multinomial regression revealed a significant year-to-year decrease in aSAH procedures compared with the control group of non-aneurysmal hospitalizations (relative risk ratio, 0.963 per year; <0.001), while there was no statistical significance for unruptured aneurysms procedures (relative risk ratio, 1.012 per year; =0.35). Conclusions With each passing year, there is a significant decrease in relative risk ratio of undergoing treatment for aSAH, concomitant with a stable annual risk of undergoing treatment for unruptured intracranial aneurysms.
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http://dx.doi.org/10.1161/JAHA.120.016998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955327PMC
February 2021

Proteome-Wide Analysis using SOMAscan Identifies and Validates Chitinase-3-Like Protein 1 as a Risk and Disease Marker of Delirium Among Older Adults Undergoing Major Elective Surgery.

J Gerontol A Biol Sci Med Sci 2021 Feb 4. Epub 2021 Feb 4.

Beth Israel Deaconess Medical Center.

Background: Delirium (an acute change in cognition) is a common, morbid, and costly syndrome seen primarily in aging adults. Despite increasing knowledge of its epidemiology, delirium remains a clinical diagnosis with no established biomarkers to guide diagnosis or management. Advances in proteomics now provide opportunities to identify novel markers of risk and disease progression for postoperative delirium and its associated long-term consequences (e.g., long term cognitive decline and Alzheimer's disease [AD]).

Methods: In a nested matched case-control study (18 delirium/no-delirium pairs) within the Successful Aging after Elective Surgery study (N=556), we evaluated the association of 1,305 plasma proteins preoperatively [PREOP] and on postoperative day 2 [POD2]) with delirium using SOMAscan. Generalized linear models were applied to ELISA validation data of one protein across the full cohort. Multi-protein modeling included delirium biomarkers identified in prior work (C-reactive protein, interleukin-6 [IL6]).

Results: We identified chitinase-3-like-protein-1 (CHI3L1/YKL-40) as the sole delirium-associated protein in both a PREOP and a POD2 predictor model, a finding confirmed by ELISA. Multi-protein modeling found high PREOP CHI3L1/YKL-40 and POD2 IL6 increased the risk of delirium (relative risk [95% confidence interval] Quartile [Q]4 vs. Q1: 2.4[1.2-5.0] and 2.1[1.1-4.1], respectively).

Conclusions: Our identification of CHI3L1/YKL-40 in postoperative delirium parallels reports of CHI3L1/YKL-40 and its association with aging, mortality, and age-related conditions including AD onset and progression. This highlights the type 2 innate immune response, involving CHI3L1/YKL-40, as an underlying mechanism of postoperative delirium, a common, morbid, and costly syndrome that threatens the independence of older adults.
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http://dx.doi.org/10.1093/gerona/glaa326DOI Listing
February 2021

Targeted metabolomics analysis of postoperative delirium.

Sci Rep 2021 01 15;11(1):1521. Epub 2021 Jan 15.

Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Nebraska Hall E419, P.O. Box 880511, Lincoln, NE, 68588, USA.

Postoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls from the Successful Aging after Elective Surgery (SAGES) cohort (N = 560) of patients ≥ 70 years old without dementia undergoing scheduled major non-cardiac surgery. We applied targeted mass spectrometry with internal standards and pooled controls using a nested matched case-control study preoperatively (PREOP) and on postoperative day 2 (POD2) to identify potential delirium risk and disease markers. Univariate analyses identified 37 PREOP and 53 POD2 metabolites associated with delirium and multivariate analyses achieved significant separation between the two groups with an 11-metabolite prediction model at PREOP (AUC = 83.80%). Systems biology analysis using the metabolites with differential concentrations rendered "valine, leucine, and isoleucine biosynthesis" at PREOP and "citrate cycle" at POD2 as the most significantly enriched pathways (false discovery rate < 0.05). Perturbations in energy metabolism and amino acid synthesis pathways may be associated with postoperative delirium and suggest potential mechanisms for delirium pathogenesis. Our results could lead to the development of a metabolomic delirium predictor.
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http://dx.doi.org/10.1038/s41598-020-80412-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810737PMC
January 2021

Plasma protein expression profiles, cardiovascular disease, and religious struggles among South Asians in the MASALA study.

Sci Rep 2021 01 13;11(1):961. Epub 2021 Jan 13.

Harvard Medical School, Harvard University, 1309 Beacon Street, Brookline, MA, 02447, USA.

Blood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case-control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.
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http://dx.doi.org/10.1038/s41598-020-79429-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806901PMC
January 2021

A systematic review and meta-analysis of mindfulness- and acceptance-based interventions for affect intolerance/sensitivity.

Behav Res Ther 2020 12 28;135:103746. Epub 2020 Sep 28.

Division of General Medicine, Harvard Medical School/Beth Israel Deaconess Medical Center, 330 Brookline Avenue, CO-1309, 2nd Floor, Boston, MA, 02215, USA. Electronic address:

Affect intolerance/sensitivity, defined as one's sensitivity to, or inability to tolerate, affective states, is a transdiagnostic process implicated in the development and maintenance of numerous forms of psychopathology. Mindfulness and acceptance interventions are posited to improve affect intolerance/sensitivity; however, there has been no quantitative synthesis of this research to date. Seven electronic databases were searched up until November 2018. Hedges' g values, 95% confidence intervals, p-values, and Q-values were calculated for a series of random-effects models. Twenty-five studies (pooled N = 1778) met eligibility criteria and were included in the qualitative synthesis (n = 22 included in the meta-analysis). There was a small, significant effect of mindfulness and acceptance interventions on improving affect intolerance/sensitivity from pre-to post-intervention (Hedges' g = -0.37, 95% CI = -0.52 to -0.23, p < .001), with effects maintained up to 6-months (Hedges' g = -0.35, 95% CI = -0.61 to -0.09, p < .01). There was a significantly larger effect for studies with inactive compared to active controls. No significant effect size differences were found for intervention length (<8 vs. ≥ 8 sessions), intervention type (mindfulness vs. acceptance) or sample type (clinical vs. non-clinical). Mindfulness and acceptance interventions modestly improve affect intolerance/sensitivity.
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http://dx.doi.org/10.1016/j.brat.2020.103746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943058PMC
December 2020

Efficacy of cognitive behavioral therapy for insomnia in breast cancer: A meta-analysis.

Sleep Med Rev 2021 02 7;55:101376. Epub 2020 Sep 7.

Osher Center for Integrative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Division of General Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

Insomnia is highly prevalent among patients with breast cancer (BC). Although cognitive behavioral therapy for insomnia (CBT-I) is available in integrative oncology settings, it poses unique challenges for BC survivors. Our review aimed to assess the evidence for the therapeutic effects of CBT-I on insomnia in BC. Randomized controlled trials (RCTs) that included patients/survivors with BC and insomnia, and at least one validated self-report measure of sleep quality were included in the review. Of the 14 included RCTs (total N = 1363), the most common components incorporated in CBT-I interventions were sleep hygiene, stimulus control and sleep restriction. Pooled effect sizes favored CBT-I at post-intervention (Hedges' g = -0.779, 95% CI = -0.949, -0.609), short-term follow-up (within six months, Hedges' g = -0.653, 95% CI = -0.808, -0.498), and long-term follow-up (12 mo, Hedges' g = -0.335, 95% CI = -0.532, -0.139). In sub-analyses, CBT-I had similar effect sizes regardless of potential modifiers (comparison design, delivery formats, etc.). As an integrative oncology intervention, CBT-I is efficacious for reducing insomnia and improving sleep quality in women treated for BC, with medium-to-large effect sizes that persist after intervention delivery ends. Given the variability in the CBT-I components tested in RCTs, future studies should investigate the optimal integration of CBT-I components for managing insomnia during BC survivorship.
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http://dx.doi.org/10.1016/j.smrv.2020.101376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210529PMC
February 2021

Disparities in United States hospitalizations for serious infections in patients with and without opioid use disorder: A nationwide observational study.

PLoS Med 2020 08 7;17(8):e1003247. Epub 2020 Aug 7.

Harvard Medical School, Boston, Massachusetts, United States of America.

Background: Patients with opioid use disorder (OUD) who are hospitalized for serious infections requiring prolonged intravenous antibiotics may face barriers to discharge, which could prolong hospital length of stay (LOS) and increase financial burden. We investigated differences in LOS, discharge disposition, and charges between hospitalizations for serious infections in patients with and without OUD.

Methods And Findings: We utilized the 2016 National Inpatient Sample-a nationally representative database of all discharges from US acute care hospitals. The population of interest was all hospitalizations for infective endocarditis, epidural abscess, septic arthritis, or osteomyelitis. The exposure was OUD, and the primary outcome was LOS until discharge, assessed by using a competing risks analysis to estimate adjusted hazard ratios (aHRs). Adjusted odds ratio (aOR) of discharge disposition and adjusted differences in hospital charges were also reported. Of 95,470 estimated hospitalizations for serious infections (infective endocarditis, epidural abscess, septic arthritis, and osteomyelitis), the mean age was 49 years and 35% were female. 46% had Medicare (government-based insurance coverage for people age 65+ years), and 70% were non-Hispanic white. After adjustment for potential confounders, OUD was associated with a lower probability of discharge at any given LOS (aHR 0.61; 95% CI 0.59-0.63; p < 0.001). OUD was also associated with lower odds of discharge to home (aOR 0.38; 95% CI 0.33-0.43; p < 0.001) and higher odds of discharge to a post-acute care facility (aOR 1.85; 95% CI 1.57-2.17; p < 0.001) or patient-directed discharge (also referred to as "discharge against medical advice") (aOR 3.47; 95% CI 2.80-4.29; p < 0.001). There was no significant difference in average total hospital charges, though daily hospital charges were significantly lower for patients with OUD. Limitations include the potential for unmeasured confounders and the use of billing codes to identify cohorts.

Conclusions: Our findings suggest that among hospitalizations for some serious infections, those involving patients with OUD were associated with longer LOS, higher odds of discharge to post-acute care facilities or patient-directed discharge, and similar total hospital charges, despite lower daily charges. These findings highlight opportunities to improve care for patients with OUD hospitalized with serious infections, and to reduce the growing associated costs.
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http://dx.doi.org/10.1371/journal.pmed.1003247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413412PMC
August 2020

The Growth Rate of Subsolid Lung Adenocarcinoma Nodules at Chest CT.

Radiology 2020 10 4;297(1):189-198. Epub 2020 Aug 4.

From the Departments of Radiology (C.d.M.M., R.R.G., A.C.M.F., B.H.H., A.A.B.), General Medicine (L.H.N.), and Pathology (A.O., M.A.M., P.A.V.), Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Mass (L.H.N.); and Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria (B.H.H.).

Background Confirming that subsolid adenocarcinomas show exponential growth is important because it would justify using volume doubling time to assess their growth. Purpose To test whether the growth of lung adenocarcinomas manifesting as subsolid nodules at chest CT is accurately represented by an exponential model. Materials and Methods Patients with lung adenocarcinomas manifesting as subsolid nodules surgically resected between January 2005 and May 2018, with three or more longitudinal CT examinations before resection, were retrospectively included. Overall volume (for all nodules) and solid component volume (for part-solid nodules) were measured over time. A linear mixed-effects model was used to identify the growth pattern (linear, exponential, quadratic, or power law) that best represented growth. The interactions between nodule growth and clinical, CT morphologic, and pathologic parameters were studied. Results Sixty-nine patients (mean age, 70 years ± 9 [standard deviation]; 48 women) with 74 lung adenocarcinomas were evaluated. Overall growth and solid component growth were better represented by an exponential model (adjusted = 0.89 and 0.95, respectively) than by a quadratic model ( = 0.88 and 0.93, respectively), a linear model ( = 0.87 and 0.92, respectively), or a power law model ( = 0.82 and 0.93, respectively). Faster overall volume growth was associated with a history of lung cancer ( < .001), a baseline nodule volume less than 500 mm ( = .03), and histologic findings of invasive adenocarcinoma ( < .001). The median volume doubling time of noninvasive adenocarcinoma was significantly longer than that of invasive adenocarcinoma (939 days [interquartile range, 588-1563 days] vs 678 days [interquartile range, 392-916 days], respectively; = .01). Conclusion The overall volume growth of adenocarcinomas manifesting as subsolid nodules at chest CT was best represented by an exponential model compared with the other tested models. This justifies the use of volume doubling time for the growth assessment of these nodules. © RSNA, 2020 See also the editorial by Kuriyama and Yanagawa in this issue.
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http://dx.doi.org/10.1148/radiol.2020192322DOI Listing
October 2020

Reproducibility of Segmentation-based Myocardial Radiomic Features with Cardiac MRI.

Radiol Cardiothorac Imaging 2020 Jun 25;2(3):e190216. Epub 2020 Jun 25.

Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215 (J.J., L.H.N., J.M., S.K., J.R., P.P., B.G., R.N.); Department of Computer Science, Technical University of Munich, Munich, Germany (J.J.); and Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Mass (L.H.N.).

Purpose: To investigate reproducibility of myocardial radiomic features with cardiac MRI.

Materials And Methods: Test-retest studies were performed with a 3-T MRI system using commonly used cardiac MRI sequences of cine balanced steady-state free precession (cine bSSFP), T1-weighted and T2-weighted imaging, and quantitative T1 and T2 mapping in phantom experiments and 10 healthy participants (mean ± standard deviation age, 29 years ± 13). In addition, this study assessed repeatability in 51 patients (56 years ± 14) who underwent imaging twice during the same session. Three readers independently delineated the myocardium to investigate inter- and intraobserver reproducibility of radiomic features. A total of 1023 radiomic features were extracted by using PyRadiomics () with 11 image filters and six feature families. The intraclass correlation coefficient (ICC) was estimated to assess reproducibility and repeatability, and features with ICCs greater than or equal to 0.8 were considered reproducible.

Results: Different reproducibility patterns were observed among sequences in in vivo test-retest studies. In cine bSSFP, the gray-level run-length matrix was the most reproducible feature family, and the wavelet low-pass filter applied horizontally and vertically was the most reproducible image filter. In T1 and T2 maps, intensity-based statistics (first-order) and gray-level co-occurrence matrix features were the most reproducible feature families, without a dominant reproducible image filter. Across all sequences, gray-level nonuniformity was the most frequently identified reproducible feature name. In inter- and intraobserver reproducibility studies, respectively, only 32%-47% and 61%-73% of features were identified as reproducible.

Conclusion: Only a small subset of myocardial radiomic features was reproducible, and these reproducible radiomic features varied among different sequences. © RSNA, 2020See also the commentary by Leiner in this issue.
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http://dx.doi.org/10.1148/ryct.2020190216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377242PMC
June 2020

T Mapping Tissue Heterogeneity Provides Improved Risk Stratification for ICDs Without Needing Gadolinium in Patients With Dilated Cardiomyopathy.

JACC Cardiovasc Imaging 2020 09 9;13(9):1917-1930. Epub 2020 Jul 9.

Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. Electronic address:

Objectives: This study sought to determine whether myocardial tissue heterogeneity scanned by native T mapping could improve risk stratification in patients with nonischemic dilated cardiomyopathy (NICM) evaluated for primary prevention by ICD.

Background: The benefit of insertable cardiac-defibrillator (ICD) as primary prevention ICD in patients with NICM remains to be fully clarified.

Methods: A total of 115 NICM candidates for primary prevention and 55 healthy controls with similar distributions of age and sex were prospectively enrolled. Imaging was performed at 1.5-T using a protocol that included cine magnetic resonance for left ventricular function, late gadolinium enhancement (LGE) for focal scarring, and 5-slice native T mapping for diffuse fibrosis and heterogeneity. The last method was assessed by mean absolute deviation of the segmental pixel-SD from the average pixel-SD (Mad-SD). The primary endpoint was a composite of appropriate ICD therapy and sudden cardiac death.

Results: During a median follow-up of 24 months, 13 patients (11%) experienced the primary endpoint. Dichotomized Mad-SD >0.24 provided a comparable outcome to the presence of LGE for the primary endpoint (annual event rate: 9.8% vs. 10.9%). The integration of Mad-SD to global native T showed excellent arrhythmic event-free survival (annual event rate: 0%), and high sensitivity of 85% (95% confidence interval [CI]: 55% to 98%) and moderate specificity of 72% (95% CI: 62% to 80%), with a C-statistic of 0.76 (95% CI: 0.64 to 0.87), which was comparable to the presence, location, or extent of LGE in its ability to predict arrhythmic events.

Conclusions: Combined myocardium tissue heterogeneity and interstitial fibrosis assessment by native T mapping is an important predictor of ventricular tachycardia and ventricular fibrillation and provides additive risk stratification for primary prevention ICD in NICM patients without the need for gadolinium contrast.
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http://dx.doi.org/10.1016/j.jcmg.2020.03.014DOI Listing
September 2020

Apolipoprotein E genotype and the association between C-reactive protein and postoperative delirium: Importance of gene-protein interactions.

Alzheimers Dement 2020 03 4;16(3):572-580. Epub 2020 Jan 4.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Introduction: Apolipoprotein E (APOE) status may modify the risk of postoperative delirium conferred by inflammation.

Methods: We tested whether APOE modifies the established association between C-reactive protein (CRP) and delirium incidence, severity, and duration in 553 noncardiac surgical patients aged 70 and older. High postoperative plasma CRP (≥234.12 mg/L) was defined by the highest sample-based quartile. Delirium was determined using the Confusion Assessment Method and chart review, and severity was determined by the Confusion Assessment Method-Severity score.

Results: APOE ε4 carrier prevalence was 19%, and postoperative delirium occurred in 24%. The relationship between CRP and delirium incidence, severity, and duration differed by ε4 status. Among ε4 carriers, there was a strong relationship between high CRP (vs. low CRP) and delirium incidence (relative risk [95% confidence interval], 3.0 [1.4-6.7]); however, no significant association was observed among non-ε4 carriers (relative risk [95% CI], 1.2 [0.8-1.7]).

Discussion: Our findings raise the possibility that APOE ε4 carrier status may modify the relationship between postoperative day 2 CRP levels and postoperative delirium.
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http://dx.doi.org/10.1016/j.jalz.2019.09.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086383PMC
March 2020

Measurement reproducibility of slice-interleaved T1 and T2 mapping sequences over 20 months: A single center study.

PLoS One 2019 25;14(7):e0220190. Epub 2019 Jul 25.

Department of Medicine (Cardiovascular Division), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States of America.

Background: Quantifying reproducibility of native T1 and T2 mapping over a long period (> 1 year) is necessary to assess whether changes in T1 and T2 over repeated sessions in a longitudinal study are associated with variability due to underlying tissue composition or technical confounders.

Objectives: To carry out a single-center phantom study to 1) investigate measurement reproducibility of slice-interleaved T1 (STONE) and T2 mapping over 20 months, 2) quantify sources of variability, and 3) compare reproducibility and measurements against reference spin-echo measurements.

Methods: MR imaging was performed on a 1.5 Tesla Philips Achieva scanner every 2-3 weeks over 20 months using the T1MES phantom. In each session, slice-interleaved T1 and T2 mapping was repeated 3 times for 5 slices, and maps were reconstructed using both 2-parameter and 3-parameter fit models. Reproducibility between sessions, and repeatability between repetitions and slices were evaluated using coefficients of variation (CV). Different sources of variability were quantified using variance decomposition analysis. The slice-interleaved measurement was compared to the spin-echo reference and MOLLI.

Results: Slice-interleaved T1 had excellent reproducibility and repeatability with a CV < 2%. The main sources of T1 variability were temperature in 2-parameter maps, and slice in 3-parameter maps. Superior between-session reproducibility to the spin-echo T1 was shown in 2-parameter maps, and similar reproducibility in 3-parameter maps. Superior reproducibility to MOLLI T1 was also shown. Similar measurements to the spin-echo T1 were observed with linear regression slopes of 0.94-0.99, but slight underestimation. Slice-interleaved T2 showed good reproducibility and repeatability with a CV < 7%. The main source of T2 variability was slice location/orientation. Between-session reproducibility was lower than the spin-echo T2 reference and showed good measurement agreement with linear regression slopes of 0.78-1.06.

Conclusions: Slice-interleaved T1 and T2 mapping sequences yield excellent long-term reproducibility over 20 months.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220190PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658153PMC
March 2020

Changes in Myocardial Native T and T After Exercise Stress: A Noncontrast CMR Pilot Study.

JACC Cardiovasc Imaging 2020 03 17;13(3):667-680. Epub 2019 Jul 17.

Department of Medicine (Cardiovascular Division), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. Electronic address:

Objectives: This study assessed changes in myocardial native T and T values after supine exercise stress in healthy subjects and in patients with suspected ischemia as potential imaging markers of ischemia.

Background: With emerging data on the long-term retention of gadolinium in the body and brain, there is a need for an alternative noncontrast cardiovascular magnetic resonance (CMR)-based myocardial ischemia assessment.

Methods: Twenty-eight healthy adult subjects and 14 patients with coronary artery disease (CAD) referred for exercise stress and/or rest single-photon emission computed tomography/myocardial perfusion imaging (SPECT/MPI) for evaluation of chest pain were prospectively enrolled. Free-breathing myocardial native T and T mapping were performed before and after supine bicycle exercise stress using a CMR-compatible supine ergometer positioned on the MR table. Differences in T, T and T, T values were calculated as T and T reactivity, respectively.

Results: The mean exercise intensity was 104 W, with exercise duration of 6 to 12 min. After exercise, native T was increased in healthy subjects (p < 0.001). T reactivity, but not T reactivity, correlated with the rate-pressure product as the index of myocardial blood flow during exercise (r = 0.62; p < 0.001). In patients with CAD, T reactivity was associated with the severity of myocardial perfusion abnormality on SPECT/MPI (normal: 4.9%; quartiles: 3.7% to 6.3%, mild defect: 1.2%, quartiles: 0.08% to 2.5%; moderate defect: 0.45%, quartiles: -0.35% to 1.4%; severe defect: 0.35%, quartiles: -0.44% to 0.8%) and had similar potential as SPECT/MPI to detect significant CAD (>50% diameter stenosis on coronary angiography). The area under the receiver-operating characteristic curve was 0.80 versus 0.72 (p = 0.40). The optimum cutoff value of T reactivity for predicting flow-limiting stenosis was 2.5%, with a sensitivity of 83% and a specificity of 92%, a negative predictive value of 96%, a positive predictive value of 71%, and an area under the curve of 0.86.

Conclusions: Free-breathing stress/rest native T mapping, but not T mapping, can detect physiological changes in the myocardium during exercise. Our feasibility study in patients shows the potential of this technique as a method for detecting myocardial ischemia in patients with CAD without using a pharmacological stress agent.
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http://dx.doi.org/10.1016/j.jcmg.2019.05.019DOI Listing
March 2020

Local Conduction Velocity in the Presence of Late Gadolinium Enhancement and Myocardial Wall Thinning: A Cardiac Magnetic Resonance Study in a Swine Model of Healed Left Ventricular Infarction.

Circ Arrhythm Electrophysiol 2019 05;12(5):e007175

Cardiovascular Division, Department of Medicine (J.J., E.L., L.H.N., U.N., S.N., F.P., W.J.M., E.A., R.N.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.

Background: Conduction velocity (CV) is an important property that contributes to the arrhythmogenicity of the tissue substrate. The aim of this study was to investigate the association between local CV versus late gadolinium enhancement (LGE) and myocardial wall thickness in a swine model of healed left ventricular infarction.

Methods: Six swine with healed myocardial infarction underwent cardiovascular magnetic resonance imaging and electroanatomic mapping. Two healthy controls (one treated with amiodarone and one unmedicated) underwent electroanatomic mapping with identical protocols to establish the baseline CV. CV was estimated using a triangulation technique. LGE+ regions were defined as signal intensity >2 SD than the mean of remote regions, wall thinning+ as those with wall thickness <2 SD than the mean of remote regions. LGE heterogeneity was defined as SD of LGE in the local neighborhood of 5 mm and wall thickness gradient as SD within 5 mm. Cardiovascular magnetic resonance and electroanatomic mapping data were registered, and hierarchical modeling was performed to estimate the mean difference of CV (LGE+/-, wall thinning+/-), or the change of the mean of CV per unit change (LGE heterogeneity, wall thickness gradient).

Results: Significantly slower CV was observed in LGE+ (0.33±0.25 versus 0.54±0.36 m/s; P<0.001) and wall thinning+ regions (0.38±0.28 versus 0.55±0.37 m/s; P<0.001). Areas with greater LGE heterogeneity ( P<0.001) and wall thickness gradient ( P<0.001) exhibited slower CV.

Conclusions: Slower CV is observed in the presence of LGE, myocardial wall thinning, high LGE heterogeneity, and a high wall thickness gradient. Cardiovascular magnetic resonance may offer a valuable imaging surrogate for estimating CV, which may support noninvasive identification of the arrhythmogenic substrate.
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http://dx.doi.org/10.1161/CIRCEP.119.007175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613809PMC
May 2019

Readiness, Availability and Utilization of Rural Vietnamese Health Facilities for Community Based Primary Care of Non-communicable Diseases: A CrossSectional Survey of 3 Provinces in Northern Vietnam.

Int J Health Policy Manag 2019 03 1;8(3):150-157. Epub 2019 Mar 1.

Division of Global Health Equity, Brigham and Women's Hospital, Center for Primary Care, Harvard Medical School, Boston, MA, USA.

Background: Vietnam's network of commune health centers (CHCs) have historically managed acute infectious diseases and implemented national disease-specific vertical programs. Vietnam has undergone an epidemiological transition towards non-communicable diseases (NCDs). Limited data exist on Vietnamese CHC capacity to prevent, diagnose, and treat NCDs. In this paper, we assess NCD service readiness, availability, and utilization at rural CHCs in 3 provinces in northern Vietnam.

Methods: Between January 2014 and April 2014, we conducted a cross-sectional survey of a representative sample of 89 rural CHCs from 3 provinces. Our study outcomes included service readiness, availability of equipment and medications, and utilization for five NCD conditions: hypertension, diabetes, chronic pulmonary diseases, cancer, and mental illnesses.

Results: NCD service availability was limited, except for mental health. Only 25% of CHCs indicated that they conducted activities focused on NCD prevention. Patient utilization of CHCs was approximately 223 visits per month or 8 visits per day. We found a statistically significant difference (P<.05) for NCD service availability, medication availability and CHC utilization among the 3 provinces studied.

Conclusion: This is the first multi-site study on NCD service availability in Vietnam and the first study in a mountainous region consisting predominately of ethnic minorities. Despite strong government support for NCD prevention and control, Vietnam's current network of CHCs has limited NCD service capacity.
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http://dx.doi.org/10.15171/ijhpm.2018.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462192PMC
March 2019

Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan.

Ann Surg 2021 04;273(4):732-742

Harvard Medical School, Boston, MA.

Objectives: To characterize the proteomic signature of surgery in older adults and association with postoperative outcomes.

Summary Of Background Data: Circulating plasma proteins can reflect the physiological response to and clinical outcomes after surgery.

Methods: Blood plasma from older adults undergoing elective surgery was analyzed for 1305 proteins using SOMAscan. Surgery-associated proteins underwent Ingenuity Pathways Analysis. Selected surgery-associated proteins were independently validated using Luminex or enzyme-linked immunosorbent assay methods. Generalized linear models estimated correlations with postoperative outcomes.

Results: Plasma from a subcohort (n = 36) of the Successful Aging after Elective Surgery (SAGES) study was used for SOMAscan. Systems biology analysis of 110 proteins with Benjamini-Hochberg (BH) corrected P value ≤0.01 and an absolute foldchange (|FC|) ≥1.5 between postoperative day 2 (POD2) and preoperative (PREOP) identified functional pathways with major effects on pro-inflammatory proteins. Chitinase-3-like protein 1 (CHI3L1), C-reactive protein (CRP), and interleukin-6 (IL-6) were independently validated in separate validation cohorts from SAGES (n = 150 for CRP, IL-6; n = 126 for CHI3L1). Foldchange CHI3L1 and IL-6 were associated with increased postoperative complications [relative risk (RR) 1.50, 95% confidence interval (95% CI) 1.21-1.85 and RR 1.63, 95% CI 1.18-2.26, respectively], length of stay (RR 1.35, 95% CI 0.77-1.92 and RR 0.98, 95% CI 0.52-1.45), and risk of discharge to postacute facility (RR 1.15, 95% CI 1.04-1.26 and RR 1.11, 95% CI 1.04-1.18); POD2 and PREOP CRP difference was associated with discharge to postacute facility (RR 1.14, 95% CI 1.04-1.25).

Conclusion: SOMAscan can identify novel and clinically relevant surgery-induced protein changes. Ultimately, proteomics may provide insights about pathways by which surgical stress contributes to postoperative outcomes.
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http://dx.doi.org/10.1097/SLA.0000000000003283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832727PMC
April 2021

Evaluation of a Novel Preference Assessment Tool for Patients with Multiple Sclerosis.

Int J MS Care 2018 Nov-Dec;20(6):260-267

Background: We developed a preference assessment tool to help assess patient goals, values, and preferences for multiple sclerosis (MS) management. All preference items in the tool were generated by people with MS. The aim of this study was to evaluate this tool in a national sample of people with MS.

Methods: English-speaking patients with MS aged 21 to 75 years with access to the internet were recruited. Participants completed the preference tool online, which included separate modules assessing three core preference areas: treatment goals, preferences for attributes of disease-modifying therapies, and factors influencing a change in treatment. The tool generated a summary of participants' treatment goals and preferences. Immediately after viewing the summary, participants were asked to evaluate the tool. Rankings of preference domains were compared with rankings obtained in another study.

Results: In 135 people with MS who completed the tool and evaluation, the highest ranked goal was brain health (memory, thinking, brain), followed by disability concerns (walking, strength, vision). Rankings were highly similar to those in the referent study. Nearly all participants reported that the tool helped them understand their goals and priorities regarding MS and that the summary appropriately reflected what is important to them. Most participants (87%) wanted to discuss their treatment goals and priorities with their clinician.

Conclusions: This preference assessment tool successfully captured patients' goals, values, and preferences for MS treatment and could potentially be used to help patients communicate their preferences to their clinician.
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http://dx.doi.org/10.7224/1537-2073.2017-021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295881PMC
December 2018

The Association Between C-Reactive Protein and Postoperative Delirium Differs by Catechol-O-Methyltransferase Genotype.

Am J Geriatr Psychiatry 2019 01 14;27(1):1-8. Epub 2018 Sep 14.

Beth Israel Deaconess Medical Center, Boston, MA; Harvard Medical School, Boston, MA; Warren Alpert Medical School of Brown University, Providence, RI.

Objective: Catechol-O-methyltransferase (COMT), a key enzyme in degrading catecholamines associated with the stress response, may influence susceptibility to delirium. Individuals with the COMT (rs4680) Val/Val genotype (designated "warriors") withstand the onset of neuropsychiatric disorders and cognitive decline, whereas individuals with Met/Met and Val/Met genotypes ("nonwarriors") are more susceptible to these conditions. We evaluated whether COMT genotype modifies the established association between acute phase reactant (stress marker) C-reactive protein (CRP) and postoperative delirium.

Methods: This was a prospective cohort study conducted at two academic medical centers. The study involved 547 patients aged 70 or older undergoing major noncardiac surgery. We collected blood, extracted DNA, and performed COMT genotyping using allele-specific polymerase chain reaction assays, considering warriors versus nonwarriors. High plasma CRP, measured on postoperative day 2 using enzyme-linked immunosorbent assay, was defined by the highest sample-based quartile (≥234.12 mg/L). Delirium was determined using the Confusion Assessment Method, augmented by a validated chart review. We used generalized linear models adjusted for age, sex, surgery type, and race/ethnicity, stratified by COMT genotype, to determine whether the association between CRP and delirium differed by COMT.

Results: Prevalence of COMT warriors was 26%, and postoperative delirium occurred in 23%. Among COMT warriors, high CRP was not associated with delirium (relative risk [RR] 1.0, 95% confidence interval [CI] 0.4-2.6). In contrast, among nonwarriors, we found the expected relationship of high CRP and delirium (RR 1.5, 95% CI 1.1-2.2).

Conclusion: COMT warriors may be protected against the increased risk of delirium associated with high CRP on postoperative day 2. With further confirmation, COMT genotype may help target interventions for delirium prevention in the vulnerable nonwarrior group.
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http://dx.doi.org/10.1016/j.jagp.2018.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310215PMC
January 2019

Using a Deep Learning Network to Diagnose Congestive Heart Failure.

Authors:
Long H Ngo

Radiology 2019 02 6;290(2):523-524. Epub 2018 Nov 6.

From the Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard School of Public Health, 1309 Beacon St, 2nd Floor, Brookline, MA 02447.

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http://dx.doi.org/10.1148/radiol.2018182341DOI Listing
February 2019
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