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Article ; Online: Categorizing biomedical research: the basics of translation.

Flier, Jeffrey S / Loscalzo, Joseph

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2017 Volume 31, Issue 8, Page(s) 3210–3215

Abstract: ... its potential benefits to society.-Flier, J. S., Loscalzo, J. Categorizing biomedical research: the basics ...

Abstract	As biomedical research has evolved over the past century, the terminology employed to categorize it has failed to evolve in parallel to accommodate the implications of these changes. In particular, the terms basic research and translational research as used today in biomedicine seem especially problematic. Here we review the origins of these terms, analyze some of the conceptual confusions attendant to their current use, and assess some of the deleterious consequences of these confusions. We summarize that the distinction between basic and translational biomedical research is an anachronism. Elimination of this often contentious distinction would improve both the culture and the effectiveness of the scientific process, and its potential benefits to society.-Flier, J. S., Loscalzo, J. Categorizing biomedical research: the basics of translation.
MeSH term(s)	Animals ; Humans ; Interdisciplinary Studies ; Research Design/standards ; Terminology as Topic ; Translational Medical Research/classification ; Translational Medical Research/methods
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.201700303R
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Article ; Online: Dealing with Consequences of Irreproducibility and Modifying the Published Literature: Retractions versus Revisions.

Glass, David J / Flier, Jeffrey S

Cell metabolism

2017 Volume 26, Issue 5, Page(s) 695–696

Abstract: One of the barriers to revising the literature when new data are produced, demonstrating the lack of reproducibility of particular published findings, is the stigma associated with the current tools available, most notably the use of retractions. We ... ...

Abstract	One of the barriers to revising the literature when new data are produced, demonstrating the lack of reproducibility of particular published findings, is the stigma associated with the current tools available, most notably the use of retractions. We suggest an additional tool: revisions, which could be linked to prior manuscripts by the original authors and by others (upon peer review). We hope new approaches such as the ability to revise prior reports will help to keep the literature up-to-date and representative of the most complete understanding of an issue.
MeSH term(s)	Data Interpretation, Statistical ; Manuscripts as Topic ; Peer Review, Research/standards ; Publishing/standards ; Reproducibility of Results ; Research Design/standards
Language	English
Publishing date	2017-11-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2017.10.010
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Article: Impact of COVID-19 pandemic on mortality rate in memory clinic patients.

Bakker, Els D / van Maurik, Ingrid S / Zwan, Marissa D / Gillissen, Freek / van der Veere, Pieter J / Bouwman, Femke H / Pijnenburg, Yolande A L / van der Flier, Wiesje M

Alzheimer's & dementia (Amsterdam, Netherlands)

2024 Volume 16, Issue 1, Page(s) e12541

Abstract: Introduction: We investigated whether mortality in memory clinic patients changed due to coronavirus disease 2019 (COVID-19) pandemic.: Methods: We included patients from the Amsterdam Dementia Cohort: (1) : Results: Pandemic patients had a higher ...

Abstract	Introduction: We investigated whether mortality in memory clinic patients changed due to coronavirus disease 2019 (COVID-19) pandemic. Methods: We included patients from the Amsterdam Dementia Cohort: (1) Results: Pandemic patients had a higher risk of mortality than historical control patients (hazard ratio [HR] [95% confidence interval {CI}] = 1.34 [1.05-1.70]). Stratified for syndrome diagnosis, the effect remained significant in dementia patients (HR [95% CI] = 1.35 [1.03-1.78]). Excluding patients who died of COVID-19-infection, the higher mortality risk in pandemic patients attenuated (HR [95% CI] = 1.24 [0.97-1.58]). Only the difference in cause of death between pandemic patients and historical control patients for death to COVID-19-infection ( Conclusion: Memory clinic patients had increased mortality risk during COVID-19 compared to historical control patients, attributable to dementia patients. Highlights: We investigated if mortality rates in memory clinic patients changed due to COVID-19 pandemic.We included patients along the cognitive continuum, including SCD, MCI, and dementia.We used a well-balanced historical control group.Memory clinic patients had higher risk for mortality during COVID-19 lockdown.Our results indicate that excess mortality is mainly caused by death to COVID-19 infection.
Language	English
Publishing date	2024-01-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1002/dad2.12541
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Article ; Online: Malnutrition risk, outcomes, and costs among older adults undergoing elective surgical procedures: A retrospective cohort study.

Le, Bill / Flier, Suzanne / Madill, Janet / Joyes, Catherine / Dawson, Emily / Wellington, Chris / Adekunte, Shadia / Cheng, Davy / John-Baptiste, Ava

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition

2023 Volume 38, Issue 5, Page(s) 1045–1062

Abstract: Background: We examine here the association between malnutrition risk and adverse health outcomes among older adult patients undergoing elective surgical procedures.: Methods: We conducted a retrospective study using linked clinical and ... ...

Abstract	Background: We examine here the association between malnutrition risk and adverse health outcomes among older adult patients undergoing elective surgical procedures. Methods: We conducted a retrospective study using linked clinical and administrative databases. Malnutrition risk was assessed prior to surgery, defined by unintentional weight loss and decreased food intake. We performed a logistic regression analysis of the primary outcome, a composite adverse outcome measure, including death, bleeding, pneumonia, and other surgical complications. We conducted Fine-Gray proportional hazard regression analysis of hospital length of stay (LOS). We performed a generalized linear regression analysis of in-hospital cost data. All regression analyses controlled for frailty, age, sex, surgical category, and comorbidities. Results: Of a total of 3457 older adult elective surgical patients (65-102 years), 310 (9.0%) screened positive for malnutrition risk. In multivariable regression analyses, malnutrition risk was associated with an increased risk of the composite adverse outcome (odds ratio [OR] = 1.74; 95% CI = 1.25-2.39), higher hospitalization costs (relative cost = 1.84; 95% CI = 1.59-2.13), and a decreased risk of discharge from the hospital (hazard ratio = 0.67; 95% CI = 0.59-0.77) compared with those who screened negative. Conclusion: Older adult patients with malnutrition risk were at an increased risk of adverse surgical outcomes, had longer LOS in the hospital, and incurred higher costs of care. It is important to screen for malnutrition risk and refer older adults for dietetic consults prior to elective surgery.
MeSH term(s)	Humans ; Aged ; Retrospective Studies ; Databases, Factual ; Dietetics ; Elective Surgical Procedures/adverse effects ; Malnutrition/epidemiology
Language	English
Publishing date	2023-08-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	645074-x
ISSN	1941-2452 ; 0884-5336
ISSN (online)	1941-2452
ISSN	0884-5336
DOI	10.1002/ncp.11043
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Article ; Online: Adoption of C-reactive protein rapid tests for the management of acute childhood infections in hospitals in the Netherlands and England: a comparative health systems analysis.

Dewez, Juan Emmanuel / Nijman, Ruud G / Fitchett, Elizabeth J A / Li, Edmond C / Luu, Queena F / Lynch, Rebecca / Emonts, Marieke / de Groot, Ronald / van der Flier, Michiel / Philipsen, Ria / Ettelt, Stefanie / Yeung, Shunmay

BMC health services research

2024 Volume 24, Issue 1, Page(s) 351

Abstract: Background: The adoption of C-reactive protein point-of-care tests (CRP POCTs) in hospitals varies across Europe. We aimed to understand the factors that contribute to different levels of adoption of CRP POCTs for the management of acute childhood ... ...

Abstract	Background: The adoption of C-reactive protein point-of-care tests (CRP POCTs) in hospitals varies across Europe. We aimed to understand the factors that contribute to different levels of adoption of CRP POCTs for the management of acute childhood infections in two countries. Methods: Comparative qualitative analysis of the implementation of CRP POCTs in the Netherlands and England. The study was informed by the non-adoption, abandonment, spread, scale-up, and sustainability (NASSS) framework. Data were collected through document analysis and qualitative interviews with stakeholders. Documents were identified by a scoping literature review, search of websites, and through the stakeholders. Stakeholders were sampled purposively initially, and then by snowballing. Data were analysed thematically. Results: Forty-one documents resulted from the search and 46 interviews were conducted. Most hospital healthcare workers in the Netherlands were familiar with CRP POCTs as the tests were widely used and trusted in primary care. Moreover, although diagnostics were funded through similar Diagnosis Related Group reimbursement mechanisms in both countries, the actual funding for each hospital was more constrained in England. Compared to primary care, laboratory-based CRP tests were usually available in hospitals and their use was encouraged in both countries because they were cheaper. However, CRP POCTs were perceived as useful in some hospitals of the two countries in which the laboratory could not provide CRP measures 24/7 or within a short timeframe, and/or in emergency departments where expediting patient care was important. Conclusions: CRP POCTs are more available in hospitals in the Netherlands because of the greater familiarity of Dutch healthcare workers with the tests which are widely used in primary care in their country and because there are more funding constraints in England. However, most hospitals in the Netherlands and England have not adopted CRP POCTs because the alternative CRP measurements from the hospital laboratory are available in a few hours and at a lower cost.
MeSH term(s)	Child ; Humans ; Netherlands ; C-Reactive Protein/analysis ; Point-of-Care Testing ; Hospitals ; Systems Analysis
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2050434-2
ISSN	1472-6963 ; 1472-6963
ISSN (online)	1472-6963
ISSN	1472-6963
DOI	10.1186/s12913-024-10698-6
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Article: Persisterende subjectieve geheugen-klachten op middelbare leeftijd: diagnostiek en behandeling.

Verfaillie, S C J / Korten, N / van der Sluijs, M G J M / Jeuring, H W / van Oppen, P / van de Flier, W M / Overbeek, J M / Slot, R E R / Bouwman, F / Dols, A

Tijdschrift voor psychiatrie

2023 Volume 65, Issue 4, Page(s) 272–277

Abstract: A 47-year-old highly educated man without psychiatric history was referred for psychiatric evaluation because of persistent subjective cognitive decline after repeated and extensive diagnostic evaluation in an outpatient memory clinic. The patient ... ...

Title translation	Persistent subjective cognitive decline in middle age: diagnosis and treatment.
Abstract	A 47-year-old highly educated man without psychiatric history was referred for psychiatric evaluation because of persistent subjective cognitive decline after repeated and extensive diagnostic evaluation in an outpatient memory clinic. The patient developed increasing preoccupation and anxiety with memory complaints and concerns, despite repetitive negative findings from clinical investigations. This clinical case is coined as ‘neurocognitive hypochondria’, a syndrome interfacing with cogniform and illness anxiety disorders, in which obsessions and concerns about progression of unexplained memory deficits are indicated for specialized treatment. This case study provides more insight into differential diagnosis, classification according to the current DSM-5 criteria and discussion on potential treatment approaches.
MeSH term(s)	Male ; Humans ; Middle Aged ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/therapy ; Diagnosis, Differential ; Anxiety ; Anxiety Disorders ; Memory Disorders ; Neuropsychological Tests
Language	Dutch
Publishing date	2023-05-08
Publishing country	Netherlands
Document type	English Abstract ; Journal Article
ZDB-ID	604662-9
ISSN	0303-7339
ISSN	0303-7339
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Article ; Online: FGF21 protects against ischaemia reperfusion injury in normal and fatty livers.

Ma, Yong / Singhal, Garima / Chan, Suzanne S / Wang, Chaoqun / Yu, Hongjun / Yin, Bing / Pang, Jing / Malvar, Grace / Nasser, Imad / Mather, Marie L / Maratos-Flier, Eleftheria

Liver international : official journal of the International Association for the Study of the Liver

2024

Abstract: Background: Liver ischaemia/reperfusion (I/R) injury, which is an inevitable clinical problem of liver resection, liver transplantation and haemorrhagic shock. Fibroblast growth factor 21 (FGF21) was intimately coupled with multiple metabolic processes ... ...

Abstract	Background: Liver ischaemia/reperfusion (I/R) injury, which is an inevitable clinical problem of liver resection, liver transplantation and haemorrhagic shock. Fibroblast growth factor 21 (FGF21) was intimately coupled with multiple metabolic processes and proved to protect against apoptosis and inflammatory response in hepatocytes during hepatic I/R injury. However, the regulatory mechanisms of FGF21 in hepatic I/R injury remains unknown. Therefore, we hypothesize that FGF21 protects hepatic tissues from I/R injury. Methods: Blood samples were available from haemangiomas patients undergoing hepatectomy and murine liver I/R model and used to further evaluate the serum levels of FGF21 both in humans and mice. We further explored the regulatory mechanisms of FGF21 in murine liver I/R model by using FGF21-knockout mice (FGF21-KO mice) and FGF21-overexpression transgenic mice (FGF21-OE mice) fed a high-fat or ketogenic diet. Results: Our results show that the circulating levels of FGF21 were robustly decreased after liver I/R in both humans and mice. Silencing FGF21 expression with FGF21-KO mice aggravates liver injury at 6 h after 75 min of partial liver ischaemia, while FGF21-OE mice display alleviated hepatic I/R injury and inflammatory response. Compared with chow diet mice, exogenous FGF21 decreases the levels of aminotransferase, histological changes, apoptosis and inflammatory response in hepatic I/R injury treatment mice with a high-fat diet. Meanwhile, ketogenic diet mice are not sensitive to hepatic I/R injury. Conclusions: The circulating contents of FGF21 are decreased during liver warm I/R injury and exogenous FGF21 exerts hepatoprotective effects on hepatic I/R injury. Thus, FGF21 regulates hepatic I/R injury and may be a key therapeutic target.
Language	English
Publishing date	2024-03-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2102783-3
ISSN	1478-3231 ; 1478-3223
ISSN (online)	1478-3231
ISSN	1478-3223
DOI	10.1111/liv.15911
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Article ; Online: How healthy participants value additional diagnostic testing with amyloid-PET in patients diagnosed with mild cognitive impairment - a bidding game experiment.

van Maurik, I S / Bakker, E D / van Unnik, A A J M / Broulikova, H M / Zwan, M D / van de Giessen, E / Berkhof, J / Bouwman, F H / Bosmans, J E / van der Flier, W M

Alzheimer's research & therapy

2023 Volume 15, Issue 1, Page(s) 208

Abstract: Background: To estimate the perceived value of additional testing with amyloid-PET in Euros in healthy participants acting as analogue patients with mild cognitive impairment (MCI).: Methods: One thousand four hundred thirty-one healthy participants ... ...

Abstract	Background: To estimate the perceived value of additional testing with amyloid-PET in Euros in healthy participants acting as analogue patients with mild cognitive impairment (MCI). Methods: One thousand four hundred thirty-one healthy participants acting as analogue MCI patients (mean age 65 ± 8, 929 (75%) female) were recruited via the Dutch Brain Research Registry. Participants were asked to identify with a presented case (video vignette) of an MCI patient and asked whether they would prefer additional diagnostic testing with amyloid PET in this situation. If yes, respondents were asked how much they would be willing to pay for additional diagnostic testing. Monetary value was elicited via a bidding game in which participants were randomized over three conditions: (A) additional testing results in better patient management, (B) Same as condition A and a delay in institutionalization of 3 months, and (C) same as A and a delay in institutionalization of 6 months. Participants who were not willing to take a test were compared with participants who were willing to take a test using logit models. The highest monetary value per condition was analyzed using random-parameter mixed models. Results: The vast majority of participants acting as analogue MCI patients (87% (n = 1238)) preferred additional testing with amyloid PET. Participants who were not interested were more often female (OR = 1.61 95% CI [1.09-2.40]) and expressed fewer worries to get AD (OR = 0.64 [0.47-0.87]). The median "a priori" (i.e., before randomization) monetary value of additional diagnostic testing was €1500 (IQR 500-1500). If an additional amyloid PET resulted in better patient management (not further specified; condition A), participants were willing to pay a median price of €2000 (IQR = 1000-3500). Participants were willing to pay significantly more than condition A (better patient management) if amyloid-PET testing additionally resulted in a delay in institutionalization of 3 months (€530 [255-805] on top of €2000, condition B) or 6 months (€596 [187-1005] on top of €2000, condition C). Conclusions: Members of the general population acting as MCI patients are willing to pay a substantial amount of money for amyloid-PET and this increases when diagnostic testing leads to better patient management and the prospect to live longer at home.
MeSH term(s)	Female ; Humans ; Male ; Alzheimer Disease/diagnosis ; Amyloid ; Amyloid beta-Peptides ; Amyloidogenic Proteins ; Cognitive Dysfunction/diagnostic imaging ; Diagnostic Techniques and Procedures ; Healthy Volunteers ; Positron-Emission Tomography/methods ; Sensitivity and Specificity ; Middle Aged ; Aged
Chemical Substances	Amyloid ; Amyloid beta-Peptides ; Amyloidogenic Proteins
Language	English
Publishing date	2023-11-28
Publishing country	England
Document type	Randomized Controlled Trial ; Video-Audio Media ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-023-01346-y
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Article ; Online: Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles.

Nature aging

2024 Volume 4, Issue 1, Page(s) 33–47

Abstract: Alzheimer's disease (AD) is heterogenous at the molecular level. Understanding this heterogeneity is critical for AD drug development. Here we define AD molecular subtypes using mass spectrometry proteomics in cerebrospinal fluid, based on 1,058 proteins, ...

Abstract	Alzheimer's disease (AD) is heterogenous at the molecular level. Understanding this heterogeneity is critical for AD drug development. Here we define AD molecular subtypes using mass spectrometry proteomics in cerebrospinal fluid, based on 1,058 proteins, with different levels in individuals with AD (n = 419) compared to controls (n = 187). These AD subtypes had alterations in protein levels that were associated with distinct molecular processes: subtype 1 was characterized by proteins related to neuronal hyperplasticity; subtype 2 by innate immune activation; subtype 3 by RNA dysregulation; subtype 4 by choroid plexus dysfunction; and subtype 5 by blood-brain barrier impairment. Each subtype was related to specific AD genetic risk variants, for example, subtype 1 was enriched with TREM2 R47H. Subtypes also differed in clinical outcomes, survival times and anatomical patterns of brain atrophy. These results indicate molecular heterogeneity in AD and highlight the need for personalized medicine.
MeSH term(s)	Humans ; Alzheimer Disease/genetics ; Proteomics
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ISSN	2662-8465
ISSN (online)	2662-8465
DOI	10.1038/s43587-023-00550-7
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Article ; Online: Interest in genetic susceptibility testing and disclosure of AD dementia risk in cognitively normal adults: a survey study.

Waterink, Lisa / Masselink, Larissa A / van der Lee, Sven J / Visser, Leonie N C / Cleutjens, Solange / van der Schaar, Jetske / van Harten, Argonde C / Scheltens, Philip / Sikkes, Sietske A M / van der Flier, Wiesje M / Zwan, Marissa D

Alzheimer's research & therapy

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

Abstract: Background: Apolipoprotein-E (APOE) genetic testing for Alzheimer's disease is becoming more important as clinical trials are increasingly targeting individuals carrying APOE-ε4 alleles. Little is known about the interest in finding out one's genetic ... ...

Abstract	Background: Apolipoprotein-E (APOE) genetic testing for Alzheimer's disease is becoming more important as clinical trials are increasingly targeting individuals carrying APOE-ε4 alleles. Little is known about the interest in finding out one's genetic risk for Alzheimer's disease in the general population. Our objective was to examine this in a sample of cognitively normal (CN) adults within a population-based online research registry with the goal to implement APOE-ε4 status for trial recruitment. Methods: An online survey was completed by 442 CN participants between the age of 49 and 75 years (56% female) from the Dutch Brain Research Registry. The survey assessed interest in participation in research into, and disclosure of, genetic risk for dementia. The survey assessed interest in participation in research into, and disclosure of, genetic risk for dementia and knowing their genetic risk in different hypothetical risk scenarios (10%, 30%, and 50% genetic risk for dementia at age 85, corresponding to APOEε2/ε2 or ε2/ε3, APOEε3/ε4 or ε2ε4, and APOE-ε4/ε4 genotypes). Cochran's Q and post hoc McNemar tests were used to analyse differences in frequencies across scenarios. Results: Most participants were interested in participating in research into and disclosure of their genetic risk (81%). The most reported reason was to contribute to scientific research (94%). Interest was higher in males, whilst lower-educated participants were more often undecided. When provided with different risk scenarios, interest in knowing their risk was somewhat higher in the scenarios with higher risk, i.e. in the 50% (79%) compared to the 10% scenario (73%;χ Conclusions: Our findings indicate that the vast majority of CN adults participating in a research registry expresses interest in AD genetic risk research and disclosure. Interest in genetic risk disclosure is higher in scenarios corresponding to the APOE-ε4 genotype. This suggests APOE-ε4 screening within an online research registry is potentially a well-received method to accelerate inclusion for trials.
MeSH term(s)	Male ; Adult ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Alzheimer Disease/epidemiology ; Disclosure ; Genotype ; Apolipoproteins E/genetics ; Genetic Predisposition to Disease/genetics ; Apolipoprotein E4/genetics
Chemical Substances	Apolipoproteins E ; Apolipoprotein E4
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-023-01364-w
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