Publications by authors named "S D Harrison"

2,782 Publications

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CRD Editor's corner archive: April-June 2021.

Chron Respir Dis 2021 Jan-Dec;18:14799731211035461

School of Health and Life Sciences, Teesside University, Middlesbrough, UK.

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http://dx.doi.org/10.1177/14799731211035461DOI Listing
September 2021

A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes.

Nat Commun 2021 Sep 17;12(1):5503. Epub 2021 Sep 17.

Hightide Therapeutics, Rockville, MD, USA.

Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease -4.8% vs. -2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes.
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http://dx.doi.org/10.1038/s41467-021-25701-5DOI Listing
September 2021

Exploring the effectiveness of dextroamphetamine for the treatment of stimulant use disorder: a qualitative study with patients receiving injectable opioid agonist treatment.

Subst Abuse Treat Prev Policy 2021 Sep 16;16(1):68. Epub 2021 Sep 16.

School of Population and Public Health, University of British Columbia, 2206 East Mall, Vancouver, BC, V6T 1Z3, Canada.

Background: A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has been associated with higher rates of continued illicit opioid use and treatment dropout. A recent randomized controlled trial demonstrated the effectiveness of dextroamphetamine (a prescribed stimulant) at reducing craving for and use of cocaine among patients receiving injectable opioid agonist treatment. Following this evidence, dextroamphetamine has been prescribed to patients with stimulant use disorder at a clinic in Vancouver. This study investigates perceptions of the effectiveness of dextroamphetamine from the perspective of these patients.

Methods: Data were collected using small focus groups and one-on-one interviews with patients who were currently or formerly receiving dextroamphetamine (n = 20). Thematic analysis was conducted using an iterative approach, moving between data collection and analysis to search for patterns in the data across transcripts. This process led to the defining and naming of three central themes responding to the research question.

Results: Participants reported a range of stimulant use types, including cocaine (n = 8), methamphetamine (n = 8), or both (n = 4). Three central themes were identified as relating to participants' perceptions of the effectiveness of the medication: 1) achieving a substitution effect (i.e. extent to which dextroamphetamine provided a substitution for the effect they received from use of illicit stimulants); 2) Reaching a preferred dose (i.e. speed of titration and effect of the dose received); and 3) Ease of medication access (i.e. preference for take home doses (i.e. carries) vs. medication integrated into care at the clinic).

Conclusion: In the context of continued investigation of pharmacological treatments for stimulant use disorder, the present study has highlighted how the study of clinical outcomes could be extended to account for factors that contribute to perceptions of effectiveness from the perspective of patients. In practice, elements of treatment delivery (e.g. dosing and dispensation protocols) can be adjusted to allow for various scenarios (e.g. on site vs. take home dosing) by which dextroamphetamine and other pharmacological stimulants could be implemented to provide "effective" treatment for people with a wide range of treatment goals and needs.
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http://dx.doi.org/10.1186/s13011-021-00399-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444161PMC
September 2021

Isatuximab for relapsed/refractory multiple myeloma: review of key subgroup analyses from the Phase III ICARIA-MM study.

Future Oncol 2021 Sep 15. Epub 2021 Sep 15.

Department of Clinical Therapeutics, National & Kapodistrian University of Athens, Athens 157 72, Greece.

In the Phase III ICARIA-MM study (NCT02990338), the addition of the anti-CD38 monoclonal antibody isatuximab to pomalidomide and dexamethasone led to increased progression-free survival and improved response rates in patients with relapsed/refractory multiple myeloma. There is an unmet treatment need, particularly among patients with poor prognoses, including those with high-risk cytogenetics, those who have renal impairment, those who are elderly and those who are refractory to prior lines of treatment. In this review, the subgroup analyses from the ICARIA-MM study, representing subpopulations with poor prognostic factors, are discussed. Overall, the addition of isatuximab to pomalidomide and dexamethasone improved progression-free survival and disease response rates across different subgroups, regardless of prognostic factor.
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http://dx.doi.org/10.2217/fon-2021-0568DOI Listing
September 2021

Distinctive Roles of Two Acinetobactin Isomers in Challenging Host Nutritional Immunity.

mBio 2021 Sep 14:e0224821. Epub 2021 Sep 14.

Department of Chemistry, Korea University, Seoul, Republic of Korea.

The human pathogen Acinetobacter baumannii produces and utilizes acinetobactin for iron assimilation. Although two isomeric structures of acinetobactin, one featuring an oxazoline (Oxa) and the other with an isoxazolidinone (Isox) at the core, have been identified, their differential roles as virulence factors for successful infection have yet to be established. This study provides direct evidence that Oxa supplies iron more efficiently than Isox, primarily owing to its specific recognition by the cognate outer membrane receptor, BauA. The other components in the acinetobactin uptake machinery appear not to discriminate these isomers. Interestingly, Oxa was found to form a stable iron complex that is resistant to release of the chelated iron upon competition by Isox, despite their comparable apparent affinities to Fe(III). In addition, both Oxa and Isox were found to be competent iron chelators successfully scavenging iron from host metal sequestering proteins responsible for nutritional immunity. These observations collectively led us to propose a new model for acinetobactin-based iron assimilation at infection sites. Namely, Oxa is the principal siderophore mediating the core Fe(III) supply chain for A. baumannii, whereas Isox plays a minor role in the iron delivery and, alternatively, functions as an auxiliary iron collector that channels the iron pool toward Oxa. The unique siderophore utilization mechanism proposed here represents an intriguing strategy for pathogen adaptation under the various nutritional stresses encountered at infection sites. Acinetobacter baumannii has acquired antibiotic resistance at an alarming rate, and it is becoming a serious threat to society, particularly due to the paucity of effective treatment options. Acinetobactin is a siderophore of Acinetobacter baumannii, responsible for active iron supply, and it serves as a key virulence factor to counter host nutritional immunity during infection. While two acinetobactin isomers were identified, their distinctive roles for successful infection of Acinetobacter baumannii remained unsettled. This study clearly identified the isomer containing an oxazoline core as the principal siderophore based on comparative analysis of the specificity of the acinetobactin uptake machinery, the stability of the corresponding iron complexes, and the iron scavenging activity against the host iron sequestering proteins. Our findings are anticipated to stimulate efforts to discover a potent antivirulence agent against Acinetobacter baumannii that exploits the acinetobactin-based iron assimilation mechanism.
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http://dx.doi.org/10.1128/mBio.02248-21DOI Listing
September 2021
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