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Article ; Online: Isolated injury, Charlson Comorbidity Index, and transfer from another facility are associated with delay in antibiotic administration: a retrospective study of 963 patients with open fractures.

Pease, Tyler J / Ducas, G Wells / Raffetto, Michael L / Bernard, Andrew C / Martin, Jalen A / Matuszewski, Paul E

OTA international : the open access journal of orthopaedic trauma

2024 Volume 7, Issue 2, Page(s) e300

Abstract: Purpose: To identify factors associated with delays in administration and pharmacy and nursing preparation of antibiotics for patients with open fractures.: Design: Retrospective review.: Setting: Level I trauma center.: Patients: Nine hundred ... ...

Abstract	Purpose: To identify factors associated with delays in administration and pharmacy and nursing preparation of antibiotics for patients with open fractures. Design: Retrospective review. Setting: Level I trauma center. Patients: Nine hundred sixty-three adults with open fractures administered antibiotics. Main outcome measurements: Delay in antibiotic administration greater than 66 minutes from arrival and significant pharmacy-related and nursing-related delay. Results: Isolated injury, Charlson Comorbidity Index, and transfer from another facility were associated with delay in antibiotic administration greater than 66 minutes. Injury Severity Score, transfer, and trauma team activation were associated with pharmacy-related or nursing-related delay. Conclusion: Interventions to reduce antibiotic administration time for open fractures should focus on early identification of open fractures and standardization of antibiotic protocols to ensure timely administration even in complex or resource-scarce care situations. Level of evidence: Prognostic level III.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ISSN	2574-2167
ISSN (online)	2574-2167
DOI	10.1097/OI9.0000000000000300
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A long non-coding RNA

Mattiske, Deidre / Bernard, Pascal / Gradie, Paul E / Behringer, Richard R / Overbeek, Paul A / O'Neill, Rachel J / Phillips, Tiffany / Tarulli, Gerard / Pask, Andrew J

Research square

2023

Abstract: The novel long non-coding RNA (lncRNA) ...

Abstract	The novel long non-coding RNA (lncRNA)
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3098271/v1
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Article ; Online: Getting a handle on rat familiarization: The impact of handling protocols on classic tests of stress in

Bigelow, Logan J / Pope, Emily K / MacDonald, Debra S / Rock, Jessica E / Bernard, Paul B

Laboratory animals

2023 Volume 57, Issue 3, Page(s) 259–269

Abstract: ... assessments (i.e. elevated plus maze, light/dark box, open field) as well as via analysis of fecal boli counts ...

Abstract	Experimenter familiarization with laboratory rodents through handling prior to experimentation is an important practice in neurobehavioral research and is implicated in stress, study variability, and replicability. Unfortunately, different handling protocols have not been thoroughly examined. Determining optimal experimenter familiarization protocols is expected to reduce animal stress and thus improve welfare and data consistency. The impact of different handling protocols was determined through behavioral assessments (i.e. elevated plus maze, light/dark box, open field) as well as via analysis of fecal boli counts, ultrasonic vocalizations, and blood corticosterone. Male and female Sprague Dawley rats were distributed among three groups: never handled, picked-up, and handled for 5 min once daily over five days. Handled and picked-up rats spent more time in open arms and less time in closed arms of the elevated plus maze and more time in the center and less time at the perimeter of the open field compared to rats that were never handled, indicating that handled and picked-up rats were less anxious than those that were never handled. Male rats consistently defecated more frequently throughout the handling process and throughout behavioral testing, whereas females showed greater concentrations of blood corticosterone. Female rats were found to emit more 50-kHz calls and fewer 22-kHz calls compared to males. The results observed suggest that picking animals up may suffice as a handling method compared to time-intensive handling procedures, and that there are significant sex differences in response to handling.
MeSH term(s)	Rats ; Animals ; Female ; Male ; Rats, Sprague-Dawley ; Corticosterone ; Anxiety
Chemical Substances	Corticosterone (W980KJ009P)
Language	English
Publishing date	2023-01-05
Publishing country	England
Document type	Journal Article
ZDB-ID	391008-8
ISSN	1758-1117 ; 0023-6772
ISSN (online)	1758-1117
ISSN	0023-6772
DOI	10.1177/00236772221142687
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Article ; Online: The ‘wrong pocket’ problem as a barrier to the integration of telehealth in health organisations and systems

Hassane Alami / Sara E Shaw / Jean-Paul Fortin / Mathilde Savoldelli / Richard Fleet / Bernard Têtu

Digital Health, Vol

2023 Volume 9

Abstract: ... pocket). This problem is the origin of many difficulties in public policies and programmes (e.g ...

Abstract	The COVID-19 pandemic has accelerated the deployment of telehealth services in many countries around the world. It also revealed many barriers and challenges to the use of digital health technologies in health organisations and systems that have persisted for decades. One of these barriers is what is known as the ‘wrong pocket’ problem – where an organisation or sector makes expenditures and investments to address a given problem, but the benefits (return on investment) are captured by another organisation or sector (the wrong pocket). This problem is the origin of many difficulties in public policies and programmes (e.g. education, environment, justice and public health), especially in terms of sustainability and scaling-up of technology and innovation. In this essay/perspective, we address the wrong pocket problem in the context of a major telehealth project in Canada. We show how the problem of sharing investments and expenses, as well as the redistribution of economies among the different stakeholders involved, may have threatened the sustainability and scaling-up of this project, even though it has demonstrated the clinical utility and contributed to improving the health of populations. In conclusion, the wrong pocket problem may be decisive in the reduced take-up, and potential failure, of certain telehealth programmes and policies. It is not enough for a telehealth service to be clinically relevant and ‘efficient’, it must also be mutually beneficial to the various stakeholders involved, particularly in terms of the equitable sharing of costs and benefits (return on investment) associated with the implementation of this new service model. Finally, the wrong pocket concept offers a helpful lens for studying the success, sustainability, and scale-up of digital transformations in health organisations and systems. This needs to be considered in future research and evaluations in the field.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	360
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: BNC210, a negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor, demonstrates anxiolytic- and antidepressant-like effects in rodents.

O'Connor, Susan M / Sleebs, Brad E / Street, Ian P / Flynn, Bernard L / Baell, Jonathan B / Coles, Carolyn / Quazi, Nurul / Paul, Dharam / Poiraud, Etienne / Huyard, Bertrand / Wagner, Stephanie / Andriambeloson, Emile / de Souza, Errol B

Neuropharmacology

2024 Volume 246, Page(s) 109836

Abstract: This work describes the characterization of BNC210 (6-[(2,3-dihydro-1H-inden-2-yl)amino]-1-ethyl-3-(4-morpholinylcarbonyl)-1,8-naphthyridin-4(1H)-one), a selective, small molecule, negative allosteric modulator (NAM) of α7 nicotinic acetylcholine ... ...

Abstract	This work describes the characterization of BNC210 (6-[(2,3-dihydro-1H-inden-2-yl)amino]-1-ethyl-3-(4-morpholinylcarbonyl)-1,8-naphthyridin-4(1H)-one), a selective, small molecule, negative allosteric modulator (NAM) of α7 nicotinic acetylcholine receptors (α7 nAChR). With the aim to discover a non-sedating, anxiolytic compound, BNC210 was identified during phenotypic screening of a focused medicinal chemistry library using the mouse Light Dark (LD) box to evaluate anxiolytic-like activity and the mouse Open Field (OF) (dark) test to detect sedative and/or motor effects. BNC210 exhibited anxiolytic-like activity with no measurable sedative or motor effects. Electrophysiology showed that BNC210 did not induce α7 nAChR currents by itself but inhibited EC
MeSH term(s)	Rats ; Male ; Mice ; Humans ; Animals ; alpha7 Nicotinic Acetylcholine Receptor/metabolism ; Anti-Anxiety Agents/pharmacology ; Rodentia/metabolism ; Receptors, Nicotinic/metabolism ; Antidepressive Agents ; Hypnotics and Sedatives ; Allosteric Regulation
Chemical Substances	alpha7 Nicotinic Acetylcholine Receptor ; Anti-Anxiety Agents ; Receptors, Nicotinic ; Antidepressive Agents ; Hypnotics and Sedatives
Language	English
Publishing date	2024-01-06
Publishing country	England
Document type	Journal Article
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2024.109836
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Article ; Online: Potency trends of cannabis in Jamaica during the period of 2014 to 2020.

Lindsay, Carole M / Bernard, Khalia K / Hammond, Amanda M / Beckford, Sheldon / Abel, Wendel D / Brown, Paul D / Young, Lauriann E

Drug testing and analysis

2023 Volume 16, Issue 2, Page(s) 174–186

Abstract: Reports suggest that cannabis potency has dramatically increased over the last decade in the USA and Europe. Cannabinoids are the terpeno-phenolic compounds found in the cannabis plant and are responsible for its pharmacological activity. The two most ... ...

Abstract	Reports suggest that cannabis potency has dramatically increased over the last decade in the USA and Europe. Cannabinoids are the terpeno-phenolic compounds found in the cannabis plant and are responsible for its pharmacological activity. The two most prominent cannabinoids are delta-9-tetrahydrocannabinol (Δ
MeSH term(s)	Cannabis/chemistry ; Dronabinol/analysis ; Jamaica ; Cannabinoids/analysis ; Cannabidiol/analysis ; Cannabinoid Receptor Agonists ; Hallucinogens
Chemical Substances	Dronabinol (7J8897W37S) ; Cannabinoids ; Cannabidiol (19GBJ60SN5) ; Cannabinoid Receptor Agonists ; Hallucinogens
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2462336-2
ISSN	1942-7611 ; 1942-7603
ISSN (online)	1942-7611
ISSN	1942-7603
DOI	10.1002/dta.3527
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Article ; Online: The strength of our stories: a qualitative analysis of a multi-institutional GME storytelling event.

Olson, Maren E / Smith, M Lynne / Muhar, Alexandra / Paul, Trisha K / Trappey, Bernard E

Medical education online

2021 Volume 26, Issue 1, Page(s) 1929798

Abstract: ... ...

Abstract	Context
MeSH term(s)	Burnout, Professional/prevention & control ; Communication ; Education, Medical, Graduate/methods ; Faculty, Medical/psychology ; Humans ; Mental Health ; Narration ; Physicians/psychology ; Resilience, Psychological ; Students, Medical/psychology
Language	English
Publishing date	2021-06-06
Publishing country	United States
Document type	Journal Article
ISSN	1087-2981
ISSN (online)	1087-2981
DOI	10.1080/10872981.2021.1929798
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Article ; Online: Effect of CYP2D6 and CYP2C19 genotypes on atomoxetine serum levels: A study based on therapeutic drug monitoring data.

Smith, Robert Løvsletten / Molden, Espen / Bernard, Jean-Paul

British journal of clinical pharmacology

2023 Volume 89, Issue 7, Page(s) 2246–2253

Abstract: Aims: Atomoxetine is mainly metabolized by CYP2D6 while CYP2C19 plays a secondary role. It is known that patients carrying genotypes encoding decreased/absent CYP2D6 metabolism obtain higher atomoxetine concentrations and are at increased risk of ... ...

Abstract	Aims: Atomoxetine is mainly metabolized by CYP2D6 while CYP2C19 plays a secondary role. It is known that patients carrying genotypes encoding decreased/absent CYP2D6 metabolism obtain higher atomoxetine concentrations and are at increased risk of adverse effects. Here, we aimed to investigate the added effects of reduced-function CYP2C19 genotype on atomoxetine concentrations in real-world settings. Methods: Serum atomoxetine concentrations and CYP2D6/2C19 genotypes were included from a therapeutic drug monitoring service. Patients were first subgrouped according to CYP2D6 encoding normal, reduced or absent CYP2D6 metabolism, referred to as normal (NM), intermediate (IM) or poor metabolizers (PM). Then, the effect of reduced-function CYP2C19 genotypes was investigated. Genotyping of the CYP2D6 nonfunctional or reduced variant alleles comprised CYP2D63-6, 9-10 and 41. For CYP2C19, the CYP2C192 was analysed to define metabolizer phenotype. Dose-adjusted serum atomoxetine concentration was the exposure measure. Results: Using a patient cohort (n = 315), it was found that CYP2D6 IM and PM patients had 1.9-fold (95% confidence interval: 1.4-2.7) and 9.6-fold (5.9-16) higher exposure of atomoxetine compared with CYP2D6 NMs. CYP2C192 carriers had 1.5-fold (1.1-2.2) higher atomoxetine exposure than noncarriers regardless of CYP2D6 genotype. Conclusion:* CYP2D6 genotype has a great impact on atomoxetine exposure, where our real-world data suggest atomoxetine dose requirements to be around half and 1/10 in CYP2D6 IM and PM vs. NM patients, respectively. When adding CYP2C19 genotype as a factor of relevance for personalized atomoxetine dosing, CYP2C19*2 carriers should further reduce the dose by a third. These findings suggest that pre-emptive CYP2D6/CYP2C19 genotyping should be performed to individualize atomoxetine dosing and prevent adverse effects.
MeSH term(s)	Cytochrome P-450 CYP2D6/genetics ; Cytochrome P-450 CYP2D6/metabolism ; Atomoxetine Hydrochloride/adverse effects ; Cytochrome P-450 CYP2C19/genetics ; Drug Monitoring ; Genotype
Chemical Substances	Cytochrome P-450 CYP2D6 (EC 1.14.14.1) ; Atomoxetine Hydrochloride (57WVB6I2W0) ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1)
Language	English
Publishing date	2023-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.15706
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Article ; Online: NRF2 Activation in Trp53;p16-deficient Mice Drives Oral Squamous Cell Carcinoma.

Hamad, Samera H / Sellers, Rani S / Wamsley, Nathan / Zolkind, Paul / Schrank, Travis P / Major, Michael B / Weissman, Bernard E

Cancer research communications

2024 Volume 4, Issue 2, Page(s) 487–495

Abstract: Aberrant activation of the NRF2/NFE2L2 transcription factor commonly occurs in head and neck squamous cell carcinomas (HNSCC). Mouse model studies have shown that NRF2 activation alone does not result in cancer. When combined with classic oncogenes and ... ...

Abstract	Aberrant activation of the NRF2/NFE2L2 transcription factor commonly occurs in head and neck squamous cell carcinomas (HNSCC). Mouse model studies have shown that NRF2 activation alone does not result in cancer. When combined with classic oncogenes and at the right dose, NRF2 activation promotes tumor initiation and progression. Here we deleted the tumor suppressor genes p16INK4A and p53 (referred to as CP mice), which are commonly lost in human HNSCC, in the presence of a constitutively active NRF2E79Q mutant (CPN mice). NRF2E79Q expression in CPN mice resulted in squamous cell hyperplasia or dysplasia with hyperkeratosis in the esophagus, oropharynx, and forestomach. In addition, CPN mice displayed oral cavity squamous cell carcinoma (OSCC); CP mice bearing wild-type NRF2 expression did not develop oral cavity hyperplasia, dysplasia or OSCC. In both CP and CPN mice, we also observed predominantly abdominal sarcomas and carcinomas. Our data show that in the context of p53 and p16 tumor suppressor loss, NRF2 activation serves oncogenic functions to drive OSCC. CPN mice represent a new model for OSCC that closely reflects the genetics of human HNSCC. Significance: Human squamous cancers frequently show constitutive NRF2 activation, associated with poorer outcomes and resistance to multiple therapies. Here, we report the first activated NRF2-driven and human-relevant mouse model of squamous cell carcinoma that develops in the background of p16 and p53 loss. The availability of this model will lead to a clearer understanding of how NRF2 contributes to the initiation, progression, and therapeutic response of OSCC.
MeSH term(s)	Animals ; Humans ; Mice ; Carcinoma, Squamous Cell/genetics ; Disease Models, Animal ; Head and Neck Neoplasms/genetics ; Hyperplasia/genetics ; Mouth Neoplasms/genetics ; NF-E2-Related Factor 2/genetics ; Squamous Cell Carcinoma of Head and Neck/genetics ; Tumor Suppressor Protein p53/genetics ; Cyclin-Dependent Kinase Inhibitor p16/metabolism
Chemical Substances	NF-E2-Related Factor 2 ; Tumor Suppressor Protein p53 ; Cyclin-Dependent Kinase Inhibitor p16 ; Trp53 protein, mouse ; Nfe2l2 protein, mouse
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-23-0386
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The 'wrong pocket' problem as a barrier to the integration of telehealth in health organisations and systems.

Alami, Hassane / Shaw, Sara E / Fortin, Jean-Paul / Savoldelli, Mathilde / Fleet, Richard / Têtu, Bernard

Digital health

2023 Volume 9, Page(s) 20552076231169835

Abstract: ... pocket). This problem is the origin of many difficulties in public policies and programmes (e.g ...

Abstract	The COVID-19 pandemic has accelerated the deployment of telehealth services in many countries around the world. It also revealed many barriers and challenges to the use of digital health technologies in health organisations and systems that have persisted for decades. One of these barriers is what is known as the 'wrong pocket' problem - where an organisation or sector makes expenditures and investments to address a given problem, but the benefits (return on investment) are captured by another organisation or sector (the wrong pocket). This problem is the origin of many difficulties in public policies and programmes (e.g. education, environment, justice and public health), especially in terms of sustainability and scaling-up of technology and innovation. In this essay/perspective, we address the wrong pocket problem in the context of a major telehealth project in Canada. We show how the problem of sharing investments and expenses, as well as the redistribution of economies among the different stakeholders involved, may have threatened the sustainability and scaling-up of this project, even though it has demonstrated the clinical utility and contributed to improving the health of populations. In conclusion, the wrong pocket problem may be decisive in the reduced take-up, and potential failure, of certain telehealth programmes and policies. It is not enough for a telehealth service to be clinically relevant and 'efficient', it must also be mutually beneficial to the various stakeholders involved, particularly in terms of the equitable sharing of costs and benefits (return on investment) associated with the implementation of this new service model. Finally, the wrong pocket concept offers a helpful lens for studying the success, sustainability, and scale-up of digital transformations in health organisations and systems. This needs to be considered in future research and evaluations in the field.
Language	English
Publishing date	2023-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819396-9
ISSN	2055-2076
ISSN	2055-2076
DOI	10.1177/20552076231169835
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