Publications by authors named "Richard N Jones"

252 Publications

Racial and geographic disparities with gastrostomy tube placement in dementia and parkinsonian disorders.

Parkinsonism Relat Disord 2021 Aug 26;91:28-31. Epub 2021 Aug 26.

Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA; Rhode Island Hospital, Providence, RI, USA; Butler Hospital, Providence, RI, USA. Electronic address:

Introduction: Many patients with advanced dementia and Parkinson's disease and related disorders (PDRD) are receiving gastrostomy tube (GT) placement annually, despite its lack of proven benefit for preventing aspiration, enhancing nutrition, or prolonging survival. Given clinical practice variability in the care of people with neurodegenerative disorders, we sought to examine racial and geographic disparities in GT placement for these populations in the United States.

Method: Data were extracted from a publicly-available national database using diagnostic and procedural codes from 2006 to 2010. GT placement rates and odds ratios were calculated for two groups: PDRD and non-parkinsonian dementia (NPD).

Results: In the PDRD group, odds of GT placement were higher among patients coded as Black (OR 1.69, CI 0.80-3.56, p = 0.17) and Asian (OR 2.17, CI 0.70-6.78, p = 0.18) than Whites; although these tendencies did not reach statistical significance. In the NPD group, GT placement among Black patients was significantly more likely (OR 2.88, CI 1.90-4.36, p < 0.001) than their white counterparts, while Asian patients were significantly less likely (OR 0.12, CI 0.02-0.91, p = 0.04). Compared to the Northeast region, there were significantly lower odds of GT placement in the Midwest region (OR 0.37, CI 0.24-0.58, p < 0.001) in the NPD group only. No difference in odds was observed between the sexes in both groups.

Conclusion: This study showed geographic and racial disparities in GT placement among PDRD and NPD patients. Further studies should aim to clarify best practices for GT placement in PDRD and causes of practice differences within and between PDRD and NPD groups.
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http://dx.doi.org/10.1016/j.parkreldis.2021.08.016DOI Listing
August 2021

Estimating the effects of Mexico to U.S. migration on elevated depressive symptoms: evidence from pooled cross-national cohorts.

Ann Epidemiol 2021 Aug 23. Epub 2021 Aug 23.

Department of Epidemiology and Biostatistics, University of California, San Francisco.

Background: Migrating from Mexico to the U.S. is a major, stressful life event with potentially profound influences on mental health. However, estimating the health effects of migration is challenging because of differential selection into migration and time-varying confounder mediators of migration effects on health.

Methods: We pooled data from the Mexican Health and Aging Study (N=17,771) and Mexican-born U.S. Health and Retirement Study (N=898) participants to evaluate the effects of migration to the U.S. (at any age and in models for migration in childhood or adulthood) on depressive symptom-count, measured with a modified Centers for Epidemiologic Studies-Depression scale. We modeled probability of migrating in each year of life from birth to either age at initial migration to the U.S. or enrollment and used these models to calculate inverse probability of migration weights. We applied the weights to covariate-adjusted negative binomial GEE models, estimating the ratio of average symptom-count associated with migration.

Results: Mexico to U.S. migration was unrelated to depressive symptoms among men (ratio of average symptom-count= 0.98 [95% CI: 0.89, 1.08]) and women (ratio of average symptom-count=1.00 [95% CI: 0.92, 1.09]). Results were similar for migration in childhood, early adulthood, or later adulthood.

Conclusions: In this sample of older Mexican-born adults, migration to the U.S. was unrelated to depressive symptoms.
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http://dx.doi.org/10.1016/j.annepidem.2021.08.014DOI Listing
August 2021

Predictors of Caregiver Burden in Delirium: Patient and Caregiver Factors.

J Gerontol Nurs 2021 Sep 1;47(9):32-38. Epub 2021 Sep 1.

The current study examined the association of patient factors, patient/caregiver relationships, and living arrangements with caregiver burden due to delirium. The sample included a subset ( = 207) of hospitalized medical and surgical patients (aged >70 years) enrolled in the Better Assessment of Illness Study and their care-givers. The majority of caregivers were female (57%) and married (43%), and 47% reported living with the patient. Delirium occurred in 22% of the sample, and delirium severity, pre-existing cognitive impairment, and impairment of any activities of daily living (ADL) were associated with higher caregiver burden. However, only the ADL impairment of needing assistance with transfers was independently significantly associated with higher burden ( < 0.01). Child, child-in-law, and other relatives living with or apart from the patient reported significantly higher caregiver burden compared to spouse/partners ( < 0.01), indicating caregiver relationship and living arrangement are associated with burden. Future studies should examine additional factors contributing to delirium burden. [(9), 32-39.].
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http://dx.doi.org/10.3928/00989134-20210803-03DOI Listing
September 2021

Harmonization of Four Delirium Instruments: Creating Crosswalks and the Delirium Item-Bank (DEL-IB).

Am J Geriatr Psychiatry 2021 Jul 29. Epub 2021 Jul 29.

Department of Emergency Medicine (BKIH, EDB), University of Massachusetts Medical School, Worcester, MA; Department of Psychiatry and Human Behavior (BKIH, RNJ), Warren Alpert Medical School of Brown University, Providence, RI; Department of Neurology (BKIH, RNJ), Warren Alpert Medical School of Brown University, Providence, RI; Department of Public Health and Primary Care (ED, KM) , Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium; Department of Geriatrics (ED, KM), University Hospitals Leuven, Leuven, Belgium; Cognitive Impairment Research Group, Sligo Mental Health Services; Sligo, Ireland and Centre for Interventions in Infection, Inflammation & Immunity, Graduate Entry Medical School (DA), University of Limerick, Limerick, Ireland; Department of Psychiatry (EDM), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Departments of Psychiatry, and Population and Quantitative Health Sciences (EDB), University of Massachusetts Medical School, Worcester, MA; Department of Medicine (SKI), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, Aging Brain Center (SKI, RNJ, EDM), Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA.

Objectives: Over 30 instruments are in current, active use for delirium identification. In a recent systematic review, we recommended 4 commonly used and well-validated instruments for clinical and research use. The goal of this study is to harmonize the four instruments on the same metric using modern methods in psychometrics.

Design: Secondary data analysis from 3 studies, and a simulation study based on the observed data.

Setting: Hospitalized (non-ICU) adults over 65 years old in the United States, Ireland, and Belgium.

Participants: The total sample comprised 600 participants, contributing 1,623 assessments.

Measurements: Confusion Assessment Method (long-form and short-form), Delirium Observation Screening Scale, Delirium Rating Scale-Revised-98 (DRS-R-98) (total and severity scores), and Memorial Delirium Assessment Scale.

Results: Using item response theory, we linked scores across instruments, placing all four instruments and their separate scorings on the same metric (the propensity to delirium). Kappa statistics comparing agreement in delirium identification among the instruments ranged from 0.37 to 0.75, with the highest agreement between the DRS-R-98 total score and MDAS. After linking scores, we created a harmonized item bank, called the Delirium Item Bank (DEL-IB), consisting of 50 items. The DEL-IB allowed us to create six crosswalks, to allow scores to be translated across instruments.

Conclusions: With our results, individual instrument scores can be directly compared to aid in clinical decision-making, and quantitatively combined in meta-analyses.
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http://dx.doi.org/10.1016/j.jagp.2021.07.011DOI Listing
July 2021

Trends and outcomes associated with gastrostomy tube placement in common neurodegenerative disorders.

Clin Park Relat Disord 2021 23;4:100088. Epub 2020 Dec 23.

Brown University, Department of Neurology, Providence, RI, United States.

Introduction: Dysphagia causing aspiration pneumonia is a common complication in the advanced stages of neurodegenerative disorders. Historically, physicians attempted to prevent this complication with gastrostomy tube (GT) placement. Its use is supported in amyotrophic lateral sclerosis (ALS), not supported in Alzheimer's disease (AD), and without disease-specific guidelines in Parkinson's disease (PD).

Method: The rate of GT placement in these three populations over two decades, from 1990 to 2010, was calculated using a binomial regression model with the data extracted using diagnosis and procedural codes from a national database. The median length-of-stay (LOS) and discharge destinations were compared.

Results: The rate of GT placement was 6.0% lower annually in AD, 3.4% in PD, and 0.2% in ALS (all p ≤ 0.007). The analysis of hospital LOS and discharge destination showed 3.2 to 5.5 days longer LOS with GT placement in all groups (all p ≤ 0.01), and three to four times lower odds of going home with GT placement in AD and PD groups (OR 0.28, 95% CI 0.14-0.55, and OR 0.22, CI 0.11-0.42 respectively), while unchanged in ALS group (OR 1.1, 95% CI 0.6-1.9).

Conclusion: Despite the downward trend of GT placement over two decades, thousands of AD and PD patients still underwent GT placement annually, and this was associated with longer LOS in all groups and increased likelihood of being discharged to a nursing facility in AD and PD. Further research is necessary to understand the effects of GT on physician practices and patient expectations in advanced AD and PD.
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http://dx.doi.org/10.1016/j.prdoa.2020.100088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299983PMC
December 2020

Effects of single-dose L-theanine on motor cortex excitability.

Clin Neurophysiol 2021 Sep 10;132(9):2062-2064. Epub 2021 Jul 10.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Butler Hospital, Providence, RI, USA.

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http://dx.doi.org/10.1016/j.clinph.2021.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384717PMC
September 2021

Differential Item Functioning Analyses of the Patient-Reported Outcomes Measurement Information System (PROMIS®) Measures: Methods, Challenges, Advances, and Future Directions.

Psychometrika 2021 Sep 12;86(3):674-711. Epub 2021 Jul 12.

University of Minnesota, Minneapolis, MN, USA.

Several methods used to examine differential item functioning (DIF) in Patient-Reported Outcomes Measurement Information System (PROMIS®) measures are presented, including effect size estimation. A summary of factors that may affect DIF detection and challenges encountered in PROMIS DIF analyses, e.g., anchor item selection, is provided. An issue in PROMIS was the potential for inadequately modeled multidimensionality to result in false DIF detection. Section 1 is a presentation of the unidimensional models used by most PROMIS investigators for DIF detection, as well as their multidimensional expansions. Section 2 is an illustration that builds on previous unidimensional analyses of depression and anxiety short-forms to examine DIF detection using a multidimensional item response theory (MIRT) model. The Item Response Theory-Log-likelihood Ratio Test (IRT-LRT) method was used for a real data illustration with gender as the grouping variable. The IRT-LRT DIF detection method is a flexible approach to handle group differences in trait distributions, known as impact in the DIF literature, and was studied with both real data and in simulations to compare the performance of the IRT-LRT method within the unidimensional IRT (UIRT) and MIRT contexts. Additionally, different effect size measures were compared for the data presented in Section 2. A finding from the real data illustration was that using the IRT-LRT method within a MIRT context resulted in more flagged items as compared to using the IRT-LRT method within a UIRT context. The simulations provided some evidence that while unidimensional and multidimensional approaches were similar in terms of Type I error rates, power for DIF detection was greater for the multidimensional approach. Effect size measures presented in Section 1 and applied in Section 2 varied in terms of estimation methods, choice of density function, methods of equating, and anchor item selection. Despite these differences, there was considerable consistency in results, especially for the items showing the largest values. Future work is needed to examine DIF detection in the context of polytomous, multidimensional data. PROMIS standards included incorporation of effect size measures in determining salient DIF. Integrated methods for examining effect size measures in the context of IRT-based DIF detection procedures are still in early stages of development.
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http://dx.doi.org/10.1007/s11336-021-09775-0DOI Listing
September 2021

Double blind randomized controlled trial of deep brain stimulation for obsessive-compulsive disorder: Clinical trial design.

Contemp Clin Trials Commun 2021 Jun 5;22:100785. Epub 2021 Jun 5.

Butler Hospital, 345 Blackstone Blvd, Providence, RI, 02906, USA.

Obsessive-compulsive disorder (OCD), a leading cause of disability, affects ~1-2% of the population, and can be distressing and disabling. About 1/3 of individuals demonstrate poor responsiveness to conventional treatments. A small proportion of these individuals may be deep brain stimulation (DBS) candidates. Candidacy is assessed through a multidisciplinary process including assessment of illness severity, chronicity, and functional impact. Optimization failure, despite multiple treatments, is critical during screening. Few patients nationwide are eligible for OCD DBS and thus a multi-center approach was necessary to obtain adequate sample size. The study was conducted over a six-year period and was a NIH-funded, eight-center sham-controlled trial of DBS targeting the ventral capsule/ventral striatum (VC/VS) region. There were 269 individuals who initially contacted the sites, in order to achieve 27 participants enrolled. Study enrollment required extensive review for eligibility, which was overseen by an independent advisory board. Disabling OCD had to be persistent for ≥5 years despite exhaustive medication and behavioral treatment. The final cohort was derived from a detailed consent process that included consent monitoring. Mean illness duration was 27.2 years. OCD symptom subtypes and psychiatric comorbidities varied, but all had severe disability with impaired quality of life and functioning. Participants were randomized to receive sham or active DBS for three months. Following this period, all participants received active DBS. Treatment assignment was masked to participants and raters and assessments were blinded. The final sample was consistent in demographic characteristics and clinical features when compared to other contemporary published prospective studies of OCD DBS. We report the clinical trial design, methods, and general demographics of this OCD DBS sample.
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http://dx.doi.org/10.1016/j.conctc.2021.100785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219641PMC
June 2021

Development and internal validation of a predictive model of cognitive decline 36 months following elective surgery.

Alzheimers Dement (Amst) 2021 21;13(1):e12201. Epub 2021 May 21.

Biogen Inc Cambridge Massachusetts USA.

Introduction: Our goal was to determine if features of surgical patients, easily obtained from the medical chart or brief interview, could be used to predict those likely to experience more rapid cognitive decline following surgery.

Methods: We analyzed data from an observational study of 560 older adults (≥70 years) without dementia undergoing major elective non-cardiac surgery. Cognitive decline was measured using change in a global composite over 2 to 36 months following surgery. Predictive features were identified as variables readily obtained from chart review or a brief patient assessment. We developed predictive models for cognitive decline (slope) and predicting dichotomized cognitive decline at a clinically determined cut.

Results: In a hold-out testing set, the regularized regression predictive model achieved a root mean squared error (RMSE) of 0.146 and a model r-square ( ) of .31. Prediction of "rapid" decliners as a group achieved an area under the curve (AUC) of .75.

Conclusion: Some of our models could predict persons with increased risk for accelerated cognitive decline with greater accuracy than relying upon chance, and this result might be useful for stratification of surgical patients for inclusion in future clinical trials.
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http://dx.doi.org/10.1002/dad2.12201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140204PMC
May 2021

Moderators of Age of Diagnosis in > 20,000 Females with Autism in Two Large US Studies.

J Autism Dev Disord 2021 May 7. Epub 2021 May 7.

Developmental Disorders Genetics Research Program, Emma Pendleton Bradley Hospital, East Providence, RI, USA.

The objective of this study was to determine the clinical features that moderate a later age at ASD diagnosis in females in a large sample of females with ASD. Within two large and independent ASD datasets (> 20,000 females), females were first diagnosed with ASD 14-months later relative to males. This later age at diagnosis was moderated by a mild or atypical presentation, wherein repetitive behaviors were limited, IQ and language were broadly intact, and recognized symptoms emerged later in development. Females are at risk for a later age at ASD diagnosis and treatment implementation, and modification of early childhood ASD screening methods for females may be warranted.
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http://dx.doi.org/10.1007/s10803-021-05026-4DOI Listing
May 2021

Common biomarkers of physiologic stress and associations with delirium in patients with intracerebral hemorrhage.

J Crit Care 2021 Aug 23;64:62-67. Epub 2021 Mar 23.

Department of Neurology, Brown University, Alpert Medical School, Providence, RI, USA.

Purpose: To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury.

Materials And Methods: We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring <24 h ("early-onset") or > 24 h after presentation ("later-onset").

Results: Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5-7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1-8.2]), and troponin (OR 3.0 [95% CI 1.2-7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients.

Conclusions: Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.
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http://dx.doi.org/10.1016/j.jcrc.2021.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222110PMC
August 2021

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults.

Alzheimers Dement (N Y) 2021 17;7(1):e12125. Epub 2021 Mar 17.

Aging Brain Center, Institute for Aging Research Hebrew SeniorLife Boston Massachusetts USA.

Introduction: The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity.

Methods: Participants ( = 59) were free of clinical dementia, age 70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme-linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were  = amyloid beta (Aβ) <175 pg/mL or Aβ ratio <0.07;  = p-tau >80 pg/mL; and  = t-tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) were rated daily post-operatively for delirium and delirium severity, respectively.

Results: Aβ, tau, and p-tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM-S [mean difference (95% confidence interval)] was 1.48 points higher (0.29-2.67),  = 0.02 among the ATN positive. Delirium in the ATN-positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM-S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM-S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM-S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM-S scores.

Discussion: The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre-clinical phase, in delirium.
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http://dx.doi.org/10.1002/trc2.12125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968120PMC
March 2021

One-Year Medicare Costs Associated With Delirium in Older Patients Undergoing Major Elective Surgery.

JAMA Surg 2021 May;156(5):430-442

Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts.

Importance: Delirium is a common, serious, and potentially preventable problem for older adults, associated with adverse outcomes. Coupled with its preventable nature, these adverse sequelae make delirium a significant public health concern; understanding its economic costs is important for policy makers and health care leaders to prioritize care.

Objective: To evaluate current 1-year health care costs attributable to postoperative delirium in older patients undergoing elective surgery.

Design, Setting, And Participants: This prospective cohort study included 497 patients from the Successful Aging after Elective Surgery (SAGES) study, an ongoing cohort study of older adults undergoing major elective surgery. Patients were enrolled from June 18, 2010, to August 8, 2013. Eligible patients were 70 years or older, English-speaking, able to communicate verbally, and scheduled to undergo major surgery at 1 of 2 Harvard-affiliated hospitals with an anticipated length of stay of at least 3 days. Eligible surgical procedures included total hip or knee replacement; lumbar, cervical, or sacral laminectomy; lower extremity arterial bypass surgery; open abdominal aortic aneurysm repair; and open or laparoscopic colectomy. Data were analyzed from October 15, 2019, to September 15, 2020.

Exposures: Major elective surgery and hospitalization.

Main Outcomes And Measures: Cumulative and period-specific costs (index hospitalization, 30-day, 90-day, and 1-year follow-up) were examined using Medicare claims and extensive clinical data. Total inflation-adjusted health care costs were determined using data from Medicare administrative claims files for the 2010 to 2014 period. Delirium was rated using the Confusion Assessment Method. We also examined whether increasing delirium severity was associated with higher cumulative and period-specific costs. Delirium severity was measured with the Confusion Assessment Method-Severity long form. Regression models were used to determine costs associated with delirium after adjusting for patient demographic and clinical characteristics.

Results: Of the 566 patients who were eligible for the study, a total of 497 patients (mean [SD] age, 76.8 [5.1] years; 281 women [57%]; 461 White participants [93%]) were enrolled after exclusion criteria were applied. During the index hospitalization, 122 patients (25%) developed postoperative delirium, whereas 375 (75%) did not. Patients with delirium had significantly higher unadjusted health care costs than patients without delirium (mean [SD] cost, $146 358 [$140 469] vs $94 609 [$80 648]). After adjusting for relevant confounders, the cumulative health care costs attributable to delirium were $44 291 (95% CI, $34 554-$56 673) per patient per year, with the majority of costs coming from the first 90 days: index hospitalization ($20 327), subsequent rehospitalizations ($27 797), and postacute rehabilitation stays ($2803). Health care costs increased directly and significantly with level of delirium severity (none-mild, $83 534; moderate, $99 756; severe, $140 008), suggesting an exposure-response relationship. The adjusted mean cumulative costs attributable to severe delirium were $56 474 (95% CI, $40 927-$77 440) per patient per year. Extrapolating nationally, the health care costs attributable to postoperative delirium were estimated at $32.9 billion (95% CI, $25.7 billion-$42.2 billion) per year.

Conclusions And Relevance: These findings suggest that the economic outcomes of delirium and severe delirium after elective surgery are substantial, rivaling costs associated with cardiovascular disease and diabetes. These results highlight the need for policy imperatives to address delirium as a large-scale public health issue.
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http://dx.doi.org/10.1001/jamasurg.2020.7260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905699PMC
May 2021

Human neurons from Christianson syndrome iPSCs reveal mutation-specific responses to rescue strategies.

Sci Transl Med 2021 02;13(580)

Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.

Christianson syndrome (CS), an X-linked neurological disorder characterized by postnatal attenuation of brain growth (postnatal microcephaly), is caused by mutations in , the gene encoding endosomal Na/H exchanger 6 (NHE6). To hasten treatment development, we established induced pluripotent stem cell (iPSC) lines from patients with CS representing a mutational spectrum, as well as biologically related and isogenic control lines. We demonstrated that pathogenic mutations lead to loss of protein function by a variety of mechanisms: The majority of mutations caused loss of mRNA due to nonsense-mediated mRNA decay; however, a recurrent, missense mutation (the G383D mutation) had both loss-of-function and dominant-negative activities. Regardless of mutation, all patient-derived neurons demonstrated reduced neurite growth and arborization, likely underlying diminished postnatal brain growth in patients. Phenotype rescue strategies showed mutation-specific responses: A gene transfer strategy was effective in nonsense mutations, but not in the G383D mutation, wherein residual protein appeared to interfere with rescue. In contrast, application of exogenous trophic factors (BDNF or IGF-1) rescued arborization phenotypes across all mutations. These results may guide treatment development in CS, including gene therapy strategies wherein our data suggest that response to treatment may be dictated by the class of mutation.
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http://dx.doi.org/10.1126/scitranslmed.aaw0682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888381PMC
February 2021

Development and validation of language and visuospatial composite scores in ADNI.

Alzheimers Dement (N Y) 2020 5;6(1):e12072. Epub 2020 Dec 5.

Department of Medicine University of Washington Seattle Washington USA.

Introduction: Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults.

Methods: We used item response theory to derive composite measures for language (ADNI-Lan) and visuospatial functioning (ADNI-VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress.

Results: ADNI-Lan and ADNI-VS were able to detect change over time and predict conversion from MCI to AD. They were associated with most of the pre-specified magnetic resonance imaging measures. ADNI-Lan had strong associations with a cerebrospinal fluid biomarker pattern.

Discussion: ADNI-Lan and ADNI-VS may be useful composites for language and visuospatial functioning in ADNI.
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http://dx.doi.org/10.1002/trc2.12072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718716PMC
December 2020

You say tomato, I say radish: can brief cognitive assessments in the US Health Retirement Study be harmonized with its International Partner Studies?

J Gerontol B Psychol Sci Soc Sci 2020 Nov 29. Epub 2020 Nov 29.

Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI, USA.

Objectives: To characterize the extent to which brief cognitive assessments administered in the population-representative US Health and Retirement Study (HRS) and its International Partner Studies can be considered to be measuring a single, unidimensional latent cognitive function construct.

Method: Cognitive function assessments were administered in face-to-face interviews in 12 studies in 26 countries (N=155,690), including the US HRS and selected International Partner Studies. We used the time point of first cognitive assessment for each study to minimize differential practice effects across studies, and documented cognitive test item coverage across studies. Using confirmatory factor analysis models, we estimated single factor general cognitive function models, and bifactor models representing memory-specific and non-memory-specific cognitive domains for each study. We evaluated model fits and factor loadings across studies.

Results: Despite relatively sparse and inconsistent cognitive item coverage across studies, all studies had some cognitive test items in common with other studies. In all studies, the bifactor models with a memory-specific domain fit better than single factor general cognitive function models. The data fit the models at reasonable thresholds for single factor models in six of the 12 studies, and for the bifactor models in all 12 of the 12 studies.

Discussion: The cognitive assessments in the US HRS and its International Partner Studies reflect comparable underlying cognitive constructs. We discuss the assumptions underlying our methods, present alternatives, and future directions for cross-national harmonization of cognitive aging data.
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http://dx.doi.org/10.1093/geronb/gbaa205DOI Listing
November 2020

Detecting Delirium: A Systematic Review of Identification Instruments for Non-ICU Settings.

J Am Geriatr Soc 2021 02 2;69(2):547-555. Epub 2020 Nov 2.

Departments of Psychiatry and Human Behavior and Neurology, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.

Background/objectives: Delirium manifests clinically in varying ways across settings. More than 40 instruments currently exist for characterizing the different manifestations of delirium. We evaluated all delirium identification instruments according to their psychometric properties and frequency of citation in published research.

Design: We conducted the systematic review by searching Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Excerpta Medica Database (Embase), PsycINFO, PubMed, and Web of Science from January 1, 1974, to January 31, 2020, with the keywords "delirium" and "instruments," along with their known synonyms. We selected only systematic reviews, meta-analyses, or narrative literature reviews including multiple delirium identification instruments.

Measurements: Two reviewers assessed the eligibility of articles and extracted data on all potential delirium identification instruments. Using the original publication on each instrument, the psychometric properties were examined using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) framework.

Results: Of 2,542 articles identified, 75 met eligibility criteria, yielding 30 different delirium identification instruments. A count of citations was determined using Scopus for the original publication for each instrument. Each instrument underwent methodological quality review of psychometric properties using COSMIN definitions. An expert panel categorized key domains for delirium identification based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III through DSM-5. Four instruments were notable for having at least two of three of the following: citation count of 200 or more, strong validation methodology in their original publication, and fulfillment of DSM-5 criteria. These were, alphabetically, Confusion Assessment Method, Delirium Observation Screening Scale, Delirium Rating Scale-Revised-98, and Memorial Delirium Assessment Scale.

Conclusion: Four commonly used and well-validated instruments can be recommended for clinical and research use. An important area for future investigation is to harmonize these measures to compare and combine studies on delirium.
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http://dx.doi.org/10.1111/jgs.16879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902461PMC
February 2021

Machine Learning to Develop and Internally Validate a Predictive Model for Post-operative Delirium in a Prospective, Observational Clinical Cohort Study of Older Surgical Patients.

J Gen Intern Med 2021 02 19;36(2):265-273. Epub 2020 Oct 19.

Department of Psychiatry & Human Behavior, and Neurology, Brown University Warren Alpert Medical School, Providence, RI, USA.

Background: Our objective was to assess the performance of machine learning methods to predict post-operative delirium using a prospective clinical cohort.

Methods: We analyzed data from an observational cohort study of 560 older adults (≥ 70 years) without dementia undergoing major elective non-cardiac surgery. Post-operative delirium was determined by the Confusion Assessment Method supplemented by a medical chart review (N = 134, 24%). Five machine learning algorithms and a standard stepwise logistic regression model were developed in a training sample (80% of participants) and evaluated in the remaining hold-out testing sample. We evaluated three overlapping feature sets, restricted to variables that are readily available or minimally burdensome to collect in clinical settings, including interview and medical record data. A large feature set included 71 potential predictors. A smaller set of 18 features was selected by an expert panel using a consensus process, and this smaller feature set was considered with and without a measure of pre-operative mental status.

Results: The area under the receiver operating characteristic curve (AUC) was higher in the large feature set conditions (range of AUC, 0.62-0.71 across algorithms) versus the selected feature set conditions (AUC range, 0.53-0.57). The restricted feature set with mental status had intermediate AUC values (range, 0.53-0.68). In the full feature set condition, algorithms such as gradient boosting, cross-validated logistic regression, and neural network (AUC = 0.71, 95% CI 0.58-0.83) were comparable with a model developed using traditional stepwise logistic regression (AUC = 0.69, 95% CI 0.57-0.82). Calibration for all models and feature sets was poor.

Conclusions: We developed machine learning prediction models for post-operative delirium that performed better than chance and are comparable with traditional stepwise logistic regression. Delirium proved to be a phenotype that was difficult to predict with appreciable accuracy.
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http://dx.doi.org/10.1007/s11606-020-06238-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878663PMC
February 2021

Depression screening in cognitively normal older adults: Measurement bias according to subjective memory decline, brain amyloid burden, cognitive function, and sex.

Alzheimers Dement (Amst) 2020 28;12(1):e12107. Epub 2020 Sep 28.

Department of Psychiatry, Alpert Medical School Brown University Providence Rhode Island USA.

Introduction: Understanding the associations among depression, subjective cognitive decline, and prodromal Alzheimer's disease (AD) has important implications for both depression and dementia screening in older adults. The Geriatric Depression Scale (GDS) is a depression screening tool for older adults that queries memory concerns. To determine whether depression symptoms on the GDS (15-item version), including self-reported memory problems, differ by levels of brain amyloid beta (Aβ), a pathological hallmark of early stage AD, we investigated potential measurement bias with regard to Aβ level. We also examined measurement bias attributable to level of cognitive functioning and sex as positive controls.

Methods: We examined 3961 cognitively normal older adults from the A4/LEARN Study. We used the MIMIC (multiple indicators, multiple causes) approach to detect measurement bias.

Results: We found measurement bias with small-to-moderate range effect sizes in several GDS-15 items with respect to Aβ level, cognitive functioning, and sex. There was negligible impact of measurement bias attributable to Aβ level on overall depressive symptom level.

Discussion: GDS-15 item responses are sensitive to Aβ burden, cognitive functioning, and sex over and above what would be expected given the effect of those factors on depressive symptom severity overall. However, these direct effects for GDS item measurement bias are of small magnitude and do not appreciably impact the validity of inferences about depression based on the GDS-15.
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http://dx.doi.org/10.1002/dad2.12107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521597PMC
September 2020

Quantifying Lifecourse Drivers of International Migration: A Cross-national Analysis of Mexico and the United States.

Epidemiology 2021 01;32(1):50-60

Department of Epidemiology and Biostatistics, University of California, San Francisco.

Background: Evaluating the long-term health consequences of migration requires longitudinal data on migrants and non-migrants to facilitate adjustment for time-varying confounder-mediators of the effect of migration on health.

Methods: We merged harmonized data on subjects aged 50+ from the US-based Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Our exposed group includes MHAS-return migrants (n = 1555) and HRS Mexican-born migrants (n = 924). Our unexposed group includes MHAS-never migrants (n = 16,954). We constructed a lifecourse data set from birth (age 0) until either age at migration to the United States or age at study entry. To account for confounding via inverse probability of treatment weights (IPTW), we modeled the probability of migration at each year of life using time-varying pre-migration characteristics. We then evaluated the effect of migration on mortality hazard estimated with and without IPTW.

Results: Mexico to the United States migration was predicted by time-varying factors that occurred before migration. Using measured covariates at time of enrollment to account for selective migration, we estimated that, for women, migrating reduces mortality risk by 13%, although this estimate was imprecise and results were compatible with either large protective or deleterious associations (hazard ratio [HR] =0.87, 95% confidence interval [CI]: 0.60, 1.27). When instead using IPTWs, the estimated effect on mortality was similarly imprecise (HR = 0.98, 95% CI: 0.77, 1.25). The relationship among men was similarly uncertain in both models.

Conclusions: Although time-varying social factors predicted migration, IPTW weighting did not affect our estimates. Larger samples are needed to precisely estimate the health effects of migration.
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http://dx.doi.org/10.1097/EDE.0000000000001266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708448PMC
January 2021

The impact of delirium on withdrawal of life-sustaining treatment after intracerebral hemorrhage.

Neurology 2020 11 10;95(20):e2727-e2735. Epub 2020 Sep 10.

From the Department of Neurology (M.E.R., S.M., K.M., S.C., B.M.G., A.M., L.C.W., B.B.T., S.S.R., C.S., L.A.D., R.N.J., K.L.F.), Department of Neurosurgery (M.E.R., A.M., L.C.W., B.B.T., S.S.R., W.F.A.), Department of Emergency Medicine (T.E.M.), Section of Medical Education (L.C.W.), and Department of Psychiatry and Human Behavior (R.N.J.), Alpert Medical School, Brown University, Providence, RI; Department of Neurology (K.N.S., D.Y.H.), Yale School of Medicine, New Haven, CT; Department of Neurology and Stroke Program (D.B.Z.), Michigan Medicine, Ann Arbor; and Department of Neurology (M.S.), Vanderbilt University School of Medicine, Nashville, TN.

Objective: To determine the impact of delirium on withdrawal of life-sustaining treatment (WLST) after intracerebral hemorrhage (ICH) in the context of established predictors of poor outcome, using data from an institutional ICH registry.

Methods: We performed a single-center cohort study on consecutive patients with ICH admitted over 12 months. ICH features were prospectively adjudicated, and WLST and corresponding hospital day were recorded retrospectively. Patients were categorized using DSM-5 criteria as never delirious, ever delirious (either on admission or later during hospitalization), or persistently comatose. We determined the impact of delirium on WLST using Cox regression models adjusted for demographics and ICH predictors (including Glasgow Coma Scale score), then used logistic regression with receiver operating characteristic curve analysis to compare the accuracy of ICH score-based models with and without delirium category in predicting WLST.

Results: Of 311 patients (mean age 70.6 ± 15.6, median ICH score 1 [interquartile range 1-2]), 50% had delirium. WLST occurred in 26%, and median time to WLST was 1 day (0-6). WLST was more frequent in patients who developed delirium (adjusted hazard ratio 8.9 [95% confidence interval (CI) 2.1-37.6]), with high rates of WLST in both early (occurring ≤24 hours from admission) and later delirium groups. An ICH score-based model was strongly predictive of WLST (area under the curve [AUC] 0.902 [95% CI 0.863-0.941]), and the addition of delirium category further improved the model's accuracy (AUC 0.936 [95% CI 0.909-0.962], = 0.004).

Conclusion: Delirium is associated with WLST after ICH regardless of when it occurs. Further study on the impact of delirium on clinician and surrogate decision-making is warranted.
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http://dx.doi.org/10.1212/WNL.0000000000010738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734724PMC
November 2020

Association of Plasma Neurofilament Light with Postoperative Delirium.

Ann Neurol 2020 11 15;88(5):984-994. Epub 2020 Sep 15.

Aging Brain Center, Hebrew SeniorLife, Boston, Massachusetts, USA.

Objective: To examine the association of the plasma neuroaxonal injury markers neurofilament light (NfL), total tau, glial fibrillary acid protein, and ubiquitin carboxyl-terminal hydrolase L1 with delirium, delirium severity, and cognitive performance.

Methods: Delirium case-no delirium control (n = 108) pairs were matched by age, sex, surgery type, cognition, and vascular comorbidities. Biomarkers were measured in plasma collected preoperatively (PREOP), and 2 days (POD2) and 30 days postoperatively (PO1MO) using Simoa technology (Quanterix, Lexington, MA). The Confusion Assessment Method (CAM) and CAM-S (Severity) were used to measure delirium and delirium severity, respectively. Cognitive function was measured with General Cognitive Performance (GCP) scores.

Results: Delirium cases had higher NfL on POD2 and PO1MO (median matched pair difference = 16.2pg/ml and 13.6pg/ml, respectively; p < 0.05). Patients with PREOP and POD2 NfL in the highest quartile (Q4) had increased risk for incident delirium (adjusted odds ratio [OR] = 3.7 [95% confidence interval (CI) = 1.1-12.6] and 4.6 [95% CI = 1.2-18.2], respectively) and experienced more severe delirium, with sum CAM-S scores 7.8 points (95% CI = 1.6-14.0) and 9.3 points higher (95% CI = 3.2-15.5). At PO1MO, delirium cases had continued high NfL (adjusted OR = 9.7, 95% CI = 2.3-41.4), and those with Q4 NfL values showed a -2.3 point decline in GCP score (-2.3 points, 95% CI = -4.7 to -0.9).

Interpretation: Patients with the highest PREOP or POD2 NfL levels were more likely to develop delirium. Elevated NfL at PO1MO was associated with delirium and greater cognitive decline. These findings suggest NfL may be useful as a predictive biomarker for delirium risk and long-term cognitive decline, and once confirmed would provide pathophysiological evidence for neuroaxonal injury following delirium. ANN NEUROL 2020;88:984-994.
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http://dx.doi.org/10.1002/ana.25889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581557PMC
November 2020

Neighborhood-Level Social Disadvantage and Risk of Delirium Following Major Surgery.

J Am Geriatr Soc 2020 12 31;68(12):2863-2871. Epub 2020 Aug 31.

Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research at the Hebrew SeniorLife, Boston, Massachusetts, USA.

Background/objectives: Delirium is a common postoperative complication associated with prolonged length of stay, hospital readmission, and premature mortality. We explored the association between neighborhood-level characteristics and delirium incidence and severity, and compared neighborhood- with individual-level indicators of socioeconomic status in predicting delirium incidence.

Design: A prospective observational cohort of patients enrolled between June 18, 2010, and August 8, 2013. Baseline interviews were conducted before surgery, and delirium/delirium severity was evaluated daily during hospitalization. Research staff evaluating delirium were blinded to baseline cognitive status.

Setting: Two academic medical centers in Boston, MA.

Participants: A total of 560 older adults, aged 70 years or older, undergoing major noncardiac surgery.

Intervention: The Area Deprivation Index (ADI) was used to characterize each neighborhood's socioeconomic disadvantage.

Measurements: Delirium was assessed using the Confusion Assessment Method (CAM) long form. Delirium severity was calculated using the highest value of CAM Severity score (CAM-S) occurring during daily hospital assessments (CAM-S Peak).

Results: Residing in the most disadvantaged neighborhoods (ADI > 44) was associated with a higher risk of incident delirium (12/26; 46%), compared with the least disadvantaged neighborhoods (122/534; 23%) (risk ratio (RR) (95% confidence interval (CI)) = 2.0 (1.3-3.1). The CAM-S Peak score was significantly associated with ADI (Spearman rank correlation, ρ = 0.11; P = .009). Mean CAM-S Peak scores generally rose from 3.7 to 5.3 across levels of increasing neighborhood disadvantage. The RR (95% CI) values associated with individual-level markers of socioeconomic status and cultural background were: 1.2 (0.9-1.7) for education of 12 years or less; 1.3 (0.8-2.1) for non-White race; and 1.7 (1.1-2.6) for annual household income of less than $20,000. None of these individual-level markers exceeded the ADI in terms of effect size or significance for prediction of delirium risk.

Conclusions: Neighborhood-level makers of social disadvantage are associated with delirium incidence and severity, and demonstrated an exposure-response relationship. Future studies should consider contextual-level metrics, such as the ADI, as risk markers of social disadvantage that can help to guide delirium treatment and prevention.
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http://dx.doi.org/10.1111/jgs.16782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744425PMC
December 2020

Education differentially contributes to cognitive reserve across racial/ethnic groups.

Alzheimers Dement 2021 01 22;17(1):70-80. Epub 2020 Aug 22.

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.

Introduction: We examined whether educational attainment differentially contributes to cognitive reserve (CR) across race/ethnicity.

Methods: A total of 1553 non-Hispanic Whites (Whites), non-Hispanic Blacks (Blacks), and Hispanics in the Washington Heights-Inwood Columbia Aging Project (WHICAP) completed structural magnetic resonance imaging. Mixture growth curve modeling was used to examine whether the effect of brain integrity indicators (hippocampal volume, cortical thickness, and white matter hyperintensity [WMH] volumes) on memory and language trajectories was modified by education across racial/ethnic groups.

Results: Higher educational attainment attenuated the negative impact of WMH burden on memory (β = -0.03; 99% CI: -0.071, -0.002) and language decline (β = -0.024; 99% CI:- 0.044, -0.004), as well as the impact of cortical thinning on level of language performance for Whites, but not for Blacks or Hispanics.

Discussion: Educational attainment does not contribute to CR similarly across racial/ethnic groups.
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http://dx.doi.org/10.1002/alz.12176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376080PMC
January 2021

Lower practice effects as a marker of cognitive performance and dementia risk: A literature review.

Alzheimers Dement (Amst) 2020 9;12(1):e12055. Epub 2020 Jul 9.

Brooklyn College and The Graduate Center of The City University of New York Brooklyn New York USA.

Background: Practice effects (PEs) are improvements in performance after repeated exposure to test materials, and typically viewed as a source of bias in repeated cognitive assessments. We aimed to determine whether characterizing PEs could also provide a useful marker of early cognitive decline.

Methods: We conducted a systematic review of the literature, searching PsycInfo (Ebsco) and PubMed databases for articles studying PEs in aging and dementia populations. Articles published between 1920 and 2019 were included.

Result: We identified 259 articles, of which 27 studied PEs as markers of cognitive performance. These studies consistently showed that smaller, less-robust PEs were associated with current diagnostic status and/or future cognitive decline. In addition, lower PEs were associated with Alzheimer's disease risk factors and neurodegeneration biomarkers.

Conclusion: PEs provide a potentially useful marker of cognitive decline, and could prove valuable as part of a cost-effective strategy to select individuals who are at-risk for dementia for future interventions.
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http://dx.doi.org/10.1002/dad2.12055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346865PMC
July 2020

The authors reply.

Crit Care Med 2020 07;48(7):e636-e637

Department of Neurology, Brown University, Alpert Medical School, Providence, RI, and Department of Neurosurgery, Brown University, Alpert Medical School, Providence, RI Department of Neurology, Brown University, Alpert Medical School, Providence, RI Department of Neurology, Brown University, Alpert Medical School, Providence, RI, and Department of Psychiatry and Human Behavior, Brown University, Alpert Medical School, Providence, RI Department of Neurology, Brown University, Alpert Medical School, Providence, RI, and Department of Neurosurgery, Brown University, Alpert Medical School, Providence, RI Department of Neurology, Brown University, Alpert Medical School, Providence, RI Department of Neurology, Brown University, Alpert Medical School, Providence, RI, and Department of Psychiatry and Human Behavior, Brown University, Alpert Medical School, Providence, RI.

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http://dx.doi.org/10.1097/CCM.0000000000004402DOI Listing
July 2020

New Delirium Severity Indicators: Generation and Internal Validation in the Better Assessment of Illness (BASIL) Study.

Dement Geriatr Cogn Disord 2020 17;49(1):77-90. Epub 2020 Jun 17.

Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA.

Background: Delirium is a common and preventable geriatric syndrome. Moving beyond the binary classification of delirium present/absent, delirium severity represents a potentially important outcome for evaluating preventive and treatment interventions and tracking the course of patients. Although several delirium severity assessment tools currently exist, most have been developed in the absence of advanced measurement methodology and have not been evaluated with rigorous validation studies.

Objective: We aimed to report our development of new delirium severity items and the results of item reduction and selection activities guided by psychometric analysis of data derived from a field study.

Methods: Building on our literature review of delirium instruments and expert panel process to identify domains of delirium severity, we adapted items from existing delirium severity instruments and generated new items. We then fielded these items among a sample of 352 older hospitalized patients.

Results: We used an expert panel process and psychometric data analysis techniques to narrow a set of 303 potential items to 17 items for use in a new delirium severity instrument. The 17-item set demonstrated good internal validity and favorable psychometric characteristics relative to comparator instruments, including the Confusion Assessment Method - Severity (CAM-S) score, the Delirium Rating Scale Revised 98, and the Memorial Delirium Assessment Scale.

Conclusion: We more fully conceptualized delirium severity and identified characteristics of an ideal delirium severity instrument. These characteristics include an instrument that is relatively quick to administer, is easy to use by raters with minimal training, and provides a severity rating with good content validity, high internal consistency reliability, and broad domain coverage across delirium symptoms. We anticipate these characteristics to be represented in the subsequent development of our final delirium severity instrument.
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http://dx.doi.org/10.1159/000506700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484102PMC
January 2021

An adapted Delphi approach: The use of an expert panel to operationally define non-judgment of internal experiences as it relates to mindfulness.

Complement Ther Med 2020 Jun 17;51:102444. Epub 2020 May 17.

Alpert Medical School of Brown University, United States; Brown University School of Public Health, United States.

Objectives: There are several definitions of mindfulness throughout the literature, many of which suggest an attitude of non-judgmental awareness. However, the concept of "non-judgment" itself has not previously been systematically operationally defined. Our purpose was to use an expert panel to generate an operational definition of non-judgment of internal experiences, as it relates to mindfulness, to be used to inform the development of an implicit measure of the construct.

Design: We utilized an adapted Delphi survey method consisting of three survey rounds.

Setting: We employed in-person and online survey methods.

Results: We used three survey rounds with an adapted Delphi approach. Expert review panelists consisted of 18 mindfulness researchers or clinicians. Each round of survey results was assessed and discussed among the core team. A consensus was reached among the core team for an operational definition of non-judgment of internal experiences: "acknowledging our thoughts, feelings, and sensations, as they are, without applying valence (e.g., good, bad, right, wrong) to them."

Conclusions: An expert panel review process informed the generation of an operational definition of non-judgment of internal experiences. Our operational definition provides a foundation for the future development of an implicit task of non-judgment of internal experiences, with the aim of using this task to assess change in response to mindfulness-based treatments. To our knowledge, this is the first systematic definition of non-judgment of internal experiences within the mindfulness literature.
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http://dx.doi.org/10.1016/j.ctim.2020.102444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299277PMC
June 2020

Correlates, Course, and Outcomes of Increased Energy in Youth with Bipolar Disorder.

J Affect Disord 2020 06 18;271:248-254. Epub 2020 Apr 18.

Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Box G-BH, Providence, RI, 02912, USA; Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02115, USA.

Objectives: Compare longitudinal trajectories of youth with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Bipolar Disorder (BD), grouped at baseline by presence/absence of increased energy during their worst lifetime mood episode (required for DSM-5).

Methods: Participants from the parent Course and Outcome of Bipolar Youth study (N = 446) were assessed utilizing The Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS), KSADS Mania Rating Scale (KMRS), and KSADS Depression Rating Scale (KDRS). Youth were grouped at baseline into those with increased energy (meeting DSM-5 Criteria A for mania) vs. without increased energy (meeting DSM-IV, but not DSM-5, Criteria A for mania), for those who had worst lifetime mood episode recorded (n = 430). Youth with available longitudinal data had the presence/absence of increased energy measured, as well as psychiatric symptomatology/clinical outcomes (evaluated via the Adolescent Longitudinal Interval Follow-Up Evaluation), at each follow-up for 12.5 years (n = 398).

Results: At baseline, the increased energy group (based on endorsed increased energy during worst lifetime mood episode; 86% of participants) vs. the without increased energy group, were more likely to meet criteria for BD-I and BD Not Otherwise Specified, had higher KMRS/KDRS total scores, and displayed poorer family/global psychosocial functioning. However, frequency of increased energy between groups was comparable after 5 years, and no significant group differences were found on clinical/psychosocial functioning outcomes after 12.5 years.

Limitations: Secondary data limited study design; groupings were based on one time point.

Conclusions: Results indicate no clinically relevant longitudinal group differences.
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http://dx.doi.org/10.1016/j.jad.2020.03.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291830PMC
June 2020

Delirium Severity Trajectories and Outcomes in ICU Patients. Defining a Dynamic Symptom Phenotype.

Ann Am Thorac Soc 2020 09;17(9):1094-1103

Center for Health Innovation and Implementation Science.

Delirium severity and duration are independently associated with higher mortality and morbidity. No studies to date have described a delirium trajectory by integrating both severity and duration. The primary aim was to develop delirium trajectories by integrating symptom severity and duration. The secondary aim was to investigate the association among trajectory membership, clinical characteristics, and 30-day mortality. A secondary analysis of the PMD (Pharmacologic Management of Delirium) randomized control trial (ClinicalTrials.gov Identifier: NCT00842608;  = 531) was conducted. The presence of delirium and symptom severity were measured at least daily for 7 days using the Confusion Assessment Method for the intensive care unit (CAM-ICU) and CAM-ICU-7 (on a scale of 0-7, with 7 being the most severe). Delirium trajectories were defined using an innovative, data-driven statistical method (group-based trajectory modeling [GBTM]) and SAS v9.4. A total of 531 delirious participants (mean age 60 yr [standard deviation = 16], 55% female, and 46% African American) were analyzed. Five distinct delirium trajectories were described (CAM-ICU-7: mean [standard deviation]); mild-brief (CAM-ICU-7: 0.5 [0.5]), severe-rapid recovers (CAM-ICU-7: 2.1 [1.0]), mild-accelerating (CAM-ICU-7: 2.2 [0.9]), severe-slow recovers (CAM-ICU-7: 3.9 [0.9]), and severe-nonrecovers (CAM-ICU-7: 5.9 [1.0]). Baseline cognition and race were associated with trajectory membership. Trajectory membership independently predicted 30-day mortality while controlling for age, sex, race, cognition, illness severity, and comorbidities. This secondary analysis described five distinct delirium trajectories based on delirium symptom severity and duration using group-based trajectory modeling. Trajectory membership predicted 30-day mortality.
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http://dx.doi.org/10.1513/AnnalsATS.201910-764OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462321PMC
September 2020
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