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Article ; Online: Prevalence and trend of central nervous system-active medication polypharmacy among US commercially insured adults with vs without early-onset dementia: a multi-year cross-sectional study.

Wei, Yu-Jung Jenny / Shrestha, Nistha / Chiang, ChienWei / DeKosky, Steven T

2024 Volume 16, Issue 1, Page(s) 30

Abstract: Background: Limited data exist on the prevalence and trend of central nervous system (CNS)-active medication polypharmacy among adults with early-onset dementia (EOD) and whether these estimates differ for adults without EOD but with chronic pain, ... ...

Abstract	Background: Limited data exist on the prevalence and trend of central nervous system (CNS)-active medication polypharmacy among adults with early-onset dementia (EOD) and whether these estimates differ for adults without EOD but with chronic pain, depression, or epilepsy, conditions managed by CNS-active medications. Methods: A multi-year, cross-sectional study using 2012-2021 MarketScan Commercial Claims data was conducted among adults aged 30 to 64 years with EOD and those without EOD but having a diagnosis of chronic pain, depression, or epilepsy as comparison groups. For each disease cohort, the primary outcome was CNS-active medication polypharmacy defined as concurrent use of ≥ 3 CNS-active medications on the US Beers Criteria list that overlapped for > 30 consecutive days during 12 months following a randomly selected medical encounter with the disease diagnosis. A separate multivariate modified Poisson regression model was used to estimate time trends in CNS polypharmacy in each disease cohort. Differences in trend estimates between EOD and non-EOD disease cohorts were examined by an interaction between EOD status and yearly time. Results: From 2013 to 2020, the annual crude prevalence of CNS polypharmacy was higher among adults with EOD (21.2%-25.0%) than adults with chronic pain (5.1%-5.9%), depression (14.8%-21.7%), or epilepsy (20.0%-22.3%). The adjusted annual prevalence of CNS polypharmacy among patients with EOD did not significantly change between 2013 and 2020 (adjusted prevalence rate ratio [aPRR], 0.94; 95% CI, 0.88-1.01), whereas a significant decreasing trend was observed among non-EOD cohorts with chronic pain (aPRR, 0.66; 95% CI, 0.63-0.69), depression (aPRR, 0.81; 95% CI, 0.77-0.85), and epilepsy (aPRR, 0.86; 95% CI, 0.83-0.89). The interaction analysis indicated that patients with epilepsy and depression (vs with EOD) had a decreasing probability of CNS-active medication polypharmacy over time (aPRR, 0.98 [95% CI, 0.98-0.99]; P < .001 for interaction for both conditions). Conclusions: The prevalence of CNS polypharmacy among US commercially insured adults with EOD (vs without) was higher and remained unchanged from 2013 to 2021. Medication reviews of adults with EOD and CNS polypharmacy are needed to ensure that benefits outweigh risks associated with combined use of these treatments.
MeSH term(s)	Humans ; Adult ; Cross-Sectional Studies ; Polypharmacy ; Chronic Pain ; Prevalence ; Dementia/drug therapy ; Dementia/epidemiology ; Epilepsy/drug therapy ; Epilepsy/epidemiology ; Central Nervous System
Language	English
Publishing date	2024-02-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-024-01405-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The Risk of Colorectal Polyps after Weight Loss Therapy Versus Obesity: A Propensity-Matched Nationwide Cohort Study.

Hussan, Hisham / McLaughlin, Eric / Chiang, Chienwei / Marsano, Joseph G / Lieberman, David

Cancers

2023 Volume 15, Issue 19

Abstract: Background: A fundamental understanding of the impact of bariatric surgery (BRS) on mechanisms of colorectal carcinogenesis is limited. For instance, studies report a reduced risk of colorectal cancer in females but not in males after BRS. We examined ... ...

Abstract	Background: A fundamental understanding of the impact of bariatric surgery (BRS) on mechanisms of colorectal carcinogenesis is limited. For instance, studies report a reduced risk of colorectal cancer in females but not in males after BRS. We examined whether this sex-specific difference existed at the earlier polyp development stage. Methods: This retrospective cohort study included 281,417 adults from the 2012-2020 MarketScan database. We compared polyps rates on colonoscopy in four groups: post- vs. pre-BRS (treatment) to post- vs. pre-severe obesity (SO) diagnosis (control). We focused our main analysis on a propensity-matched sample that yielded a balanced distribution of covariates in our four groups ( Results: Metabolic syndrome parameters improved after bariatric surgery and worsened after severe obesity diagnosis ( Conclusions: Obesity is associated with an increased risk of colorectal polyps, an effect that is ameliorated after bariatric surgery. These data are relevant for studies investigating colorectal carcinogenesis mechanisms.
Language	English
Publishing date	2023-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15194820
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Article: Generalizability of machine learning methods in detecting adverse drug events from clinical narratives in electronic medical records.

Zitu, Md Muntasir / Zhang, Shijun / Owen, Dwight H / Chiang, Chienwei / Li, Lang

Frontiers in pharmacology

2023 Volume 14, Page(s) 1218679

Abstract: We assessed the generalizability of machine learning methods using natural language processing (NLP) techniques to detect adverse drug events (ADEs) from clinical narratives in electronic medical records (EMRs). We constructed a new corpus correlating ... ...

Abstract	We assessed the generalizability of machine learning methods using natural language processing (NLP) techniques to detect adverse drug events (ADEs) from clinical narratives in electronic medical records (EMRs). We constructed a new corpus correlating drugs with adverse drug events using 1,394 clinical notes of 47 randomly selected patients who received immune checkpoint inhibitors (ICIs) from 2011 to 2018 at The Ohio State University James Cancer Hospital, annotating 189 drug-ADE relations in single sentences within the medical records. We also used data from Harvard's publicly available 2018 National Clinical Challenge (n2c2), which includes 505 discharge summaries with annotations of 1,355 single-sentence drug-ADE relations. We applied classical machine learning (support vector machine (SVM)), deep learning (convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM)), and state-of-the-art transformer-based (bidirectional encoder representations from transformers (BERT) and ClinicalBERT) methods trained and tested in the two different corpora and compared performance among them to detect drug-ADE relationships. ClinicalBERT detected drug-ADE relationships better than the other methods when trained using our dataset and tested in n2c2 (ClinicalBERT F-score, 0.78; other methods,
Language	English
Publishing date	2023-07-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1218679
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Article ; Online: Photoredox C-H functionalization leads the site-selective phenylalanine bioconjugation.

Weng, Yue / Su, Chun-Jen / Jiang, Haoyang / Chiang, Chien-Wei

Scientific reports

2022 Volume 12, Issue 1, Page(s) 18994

Abstract: Site-selectively chemical bioconjugation of peptides and proteins can improve the therapeutic exploration of modified protein drugs. Only 3.8% natural abundance of phenylalanine in protein and nearly 90% of proteins contain at least one phenylalanine ... ...

Abstract	Site-selectively chemical bioconjugation of peptides and proteins can improve the therapeutic exploration of modified protein drugs. Only 3.8% natural abundance of phenylalanine in protein and nearly 90% of proteins contain at least one phenylalanine residue in their sequenced, showing the potential in biopharmaceutical utility of the phenylalanine bioconjugation. However, the covalent bioconjugation of native phenylalanine is one of the most challenging problems in protein modification. Herein, an approach to protein modification is described that relies on a photoredox method for the site-selective bioconjugation of phenylalanine. This methodology has been validated on peptides as well as protein insulin using a straightforward and mild condition. In addition, based on characterization by near-UV CD spectroscopy and small angle X-ray scattering (SAXS), this pyrazole labeling approach permitted the insulin hexamer to completely dissociate into the monomeric form, thus making it a potential candidate for use as rapid-acting insulin for the treatment of diabetes.
MeSH term(s)	Phenylalanine/chemistry ; Scattering, Small Angle ; X-Ray Diffraction ; Proteins/chemistry ; Peptides/chemistry ; Insulin/chemistry
Chemical Substances	Phenylalanine (47E5O17Y3R) ; Proteins ; Peptides ; Insulin
Language	English
Publishing date	2022-11-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-23481-6
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Article ; Online: Reply to: Comparator choices in pharmacoepidemiology studies of Alzheimer's disease.

Zhang, Pengyue / Hou, Yuan / Chiang, Chien-Wei / Pieper, Andrew A / Cummings, Jeffrey / Cheng, Feixiong

Nature aging

2023 Volume 3, Issue 7, Page(s) 793–795

MeSH term(s)	Humans ; Alzheimer Disease/drug therapy ; Pharmacoepidemiology
Language	English
Publishing date	2023-05-22
Publishing country	United States
Document type	Letter ; Comment
ISSN	2662-8465
ISSN (online)	2662-8465
DOI	10.1038/s43587-023-00418-w
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Article ; Online: Modeling Path Importance for Effective Alzheimer's Disease Drug Repurposing.

Xiang, Shunian / Lawrence, Patrick J / Peng, Bo / Chiang, ChienWei / Kim, Dokyoon / Shen, Li / Ning, Xia

ArXiv

2023

Abstract: Recently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex ... ...

Abstract	Recently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex networks that integrate multiple interaction types, such as protein-protein interactions, to more effectively identify candidate drugs. However, existing approaches typically assume paths of the same length in the network have equal importance in identifying the therapeutic effect of drugs. Other domains have found that same length paths do not necessarily have the same importance. Thus, relying on this assumption may be deleterious to drug repurposing attempts. In this work, we propose MPI (Modeling Path Importance), a novel network-based method for AD drug repurposing. MPI is unique in that it prioritizes important paths via learned node embeddings, which can effectively capture a network's rich structural information. Thus, leveraging learned embeddings allows MPI to effectively differentiate the importance among paths. We evaluate MPI against a commonly used baseline method that identifies anti-AD drug candidates primarily based on the shortest paths between drugs and AD in the network. We observe that among the top-50 ranked drugs, MPI prioritizes 20.0% more drugs with anti-AD evidence compared to the baseline. Finally, Cox proportional-hazard models produced from insurance claims data aid us in identifying the use of etodolac, nicotine, and BBB-crossing ACE-INHs as having a reduced risk of AD, suggesting such drugs may be viable candidates for repurposing and should be explored further in future studies.
Language	English
Publishing date	2023-10-27
Publishing country	United States
Document type	Preprint
ISSN	2331-8422
ISSN (online)	2331-8422
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Article ; Online: Versatile Synthesis of Symmetric and Unsymmetric Imines via Photoelectrochemical Catalysis: Application to N-Terminal Modification of Phenylalanine.

Chiang, Chien-Wei / Li, Hung-Li / Lin, Ting-Jun / Chen, Hung-Chi / Chou, Yi-Hsien / Chou, Chih-Ju

Chemistry (Weinheim an der Bergstrasse, Germany)

2023 Volume 29, Issue 57, Page(s) e202301379

Abstract: A strategy that combines electrochemical synthesis and photoredox catalysis was reported for the efficient synthesis of imines. This approach was demonstrated to be highly versatile in producing various types of imines, including symmetric and ... ...

Abstract	A strategy that combines electrochemical synthesis and photoredox catalysis was reported for the efficient synthesis of imines. This approach was demonstrated to be highly versatile in producing various types of imines, including symmetric and unsymmetric imines, by exploring the impact of different substituents on the benzene ring of the arylamine. Additionally, the method was specifically applied to modify N-terminal phenylalanine residues and was found to be successful in the photoelectrochemical cross-coupling reaction between NH
Language	English
Publishing date	2023-09-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202301379
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Article ; Online: Comparing super-utilizers and lower-utilizers among commercial- and Medicare-insured adults with sickle cell disease.

MacEwan, Sarah R / Chiang, ChienWei / O'Brien, Sarah H / Creary, Susan / Lin, Chyongchiou J / Hyer, J Madison / Cronin, Robert M

Blood advances

2023 Volume 8, Issue 1, Page(s) 224–233

Abstract: Abstract: Sickle cell disease (SCD) is a rare but costly condition in the United States. Super-utilizers have been defined as a subset of the population with high health care encounters or expenditures. Although super-utilizers have been described in ... ...

Abstract	Abstract: Sickle cell disease (SCD) is a rare but costly condition in the United States. Super-utilizers have been defined as a subset of the population with high health care encounters or expenditures. Although super-utilizers have been described in other disease states, little is known about super-utilizers among adults with SCD. This study aimed to characterize the differences in expenditures, overall health care encounters, and pain episode encounters between super-utilizers (top 10% expenditures) and lower-utilizers with SCD (high, top 10%-24.9%; moderate, 25%-49.9%; and low, bottom 50% expenditures). A retrospective longitudinal cohort of adults with SCD were identified using validated algorithms in MarketScan and Medicare claim databases from 2016 to 2020. Encounters and expenditures were analyzed from inpatient, outpatient, and emergency department settings. Differences in encounters and expenditures between lower-utilizers and super-utilizers were compared using logistic regression. Among super-utilizers, differences in encounters and expenditures were compared according to incidences of pain episode encounters. The study population included 5666 patients with commercial insurance and 8600 with Medicare. Adjusted total annual health care expenditure was 43.46 times higher for super-utilizers than for low-utilizers among commercial-insured and 13.37 times higher in Medicare-insured patients. Among super-utilizers, there were patients with few pain episode encounters who had higher outpatient expenditures than patients with a high number of pain episode encounters. Our findings demonstrate the contribution of expensive outpatient care among SCD super-utilizers, in which analyses of high expenditure have largely focused on short-term care. Future studies are needed to better understand super-utilizers in the SCD population to inform the effective use of preventive interventions and/or curative therapies.
MeSH term(s)	Aged ; Adult ; Humans ; United States/epidemiology ; Medicare ; Retrospective Studies ; Health Expenditures ; Anemia, Sickle Cell/drug therapy ; Pain/drug therapy ; Pain/etiology
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023010813
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Article ; Online: The use of FDA-approved medications for preventing vaso-occlusive events in sickle cell disease.

Cronin, Robert M / Lin, Chyongchiou J / Chiang, ChienWei / MacEwan, Sarah R / DeBaun, Michael R / Hyer, J Madison

Blood advances

2023 Volume 7, Issue 13, Page(s) 3114–3116

MeSH term(s)	Humans ; Anemia, Sickle Cell/complications ; Anemia, Sickle Cell/drug therapy ; Pain
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008965
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Article ; Online: Modeling Path Importance for Effective Alzheimer's Disease Drug Repurposing.

Xiang, Shunian / Lawrence, Patrick J / Peng, Bo / Chiang, ChienWei / Kim, Dokyoon / Shen, Li / Ning, Xia

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing

2023 Volume 29, Page(s) 306–321

Abstract	Recently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex networks that integrate multiple interaction types, such as protein-protein interactions, to more effectively identify candidate drugs. However, existing approaches typically assume paths of the same length in the network have equal importance in identifying the therapeutic effect of drugs. Other domains have found that same length paths do not necessarily have the same importance. Thus, relying on this assumption may be deleterious to drug repurposing attempts. In this work, we propose MPI (Modeling Path Importance), a novel network-based method for AD drug repurposing. MPI is unique in that it prioritizes important paths via learned node embeddings, which can effectively capture a network's rich structural information. Thus, leveraging learned embeddings allows MPI to effectively differentiate the importance among paths. We evaluate MPI against a commonly used baseline method that identifies anti-AD drug candidates primarily based on the shortest paths between drugs and AD in the network. We observe that among the top-50 ranked drugs, MPI prioritizes 20.0% more drugs with anti-AD evidence compared to the baseline. Finally, Cox proportional-hazard models produced from insurance claims data aid us in identifying the use of etodolac, nicotine, and BBB-crossing ACE-INHs as having a reduced risk of AD, suggesting such drugs may be viable candidates for repurposing and should be explored further in future studies.
MeSH term(s)	Humans ; Alzheimer Disease/drug therapy ; Drug Repositioning/methods ; Computational Biology/methods
Language	English
Publishing date	2023-12-28
Publishing country	United States
Document type	Journal Article
ISSN	2335-6936
ISSN (online)	2335-6936
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