ORCID Profile
0000-0001-8905-2429
Current Organisation
University of Aberdeen
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Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.BONE.2010.10.177
Abstract: The acute-phase response (APR) to aminobisphosphonates is triggered by activation of γδ T cells, resulting in pro-inflammatory cytokine release. Statins prevent aminobisphosphonate-induced γδ T cell activation in vitro, raising the possibility that statins might prevent the APR in vivo. The objective of this study was to determine whether fluvastatin prevents the APR to zoledronic acid in post-menopausal women. A double-blind, randomised, placebo-controlled study was conducted in 60 healthy, post-menopausal, female volunteers (mean age 60.6 ± 4.0). Volunteers received 5 mg zoledronic acid by intravenous infusion, and either three times 40 mg fluvastatin (0 hr, 24 hr and 48 hr), 40 mg fluvastatin (0 hr) plus placebo (24 hr and 48 hr), or placebo (0 hr, 24 hr and 48 hr), orally. Post-infusion symptoms were assessed by questionnaire. Changes in γδ T cell levels, pro-inflammatory cytokines (TNFα, IFNγ, IL-6) and C-reactive protein (CRP) were measured in peripheral blood at various time-points post-infusion. Zoledronic acid administration triggered increased serum levels of TNFα, IFNγ, IL-6 and CRP in ≥70% of study volunteers, whilst characteristic APR symptoms were observed in >50% of participants. Zoledronic acid also induced a transient fall in circulating Vγ9Vδ2 T cell levels at 48 hr, consistent with Vγ9Vδ2 T cell activation. Concurrent fluvastatin administration did not prevent zoledronic acid-induced cytokine release, alter circulating Vγ9Vδ2 T cell levels, nor diminish the frequency or severity of APR symptoms. In conclusion, intravenous zoledronic acid induced pro-inflammatory cytokine release and APR symptoms in the majority of study participants, which was not prevented by co-administration of fluvastatin.
Publisher: Oxford University Press (OUP)
Date: 06-2015
Publisher: BMJ
Date: 07-2022
DOI: 10.1136/BMJOPEN-2022-062578
Abstract: Existing randomised controlled trials (RCTs) comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy have shown conflicting results. A freeze-all or a fresh transfer policy may be preferable for some couples undergoing in-vitro fertilisation (IVF), but it is unclear which couples would benefit most from each policy, how and under which protocols. Therefore, we plan a systematic review and in idual participant data meta-analysis of RCTs comparing a freeze-all and a fresh transfer policy. We will search electronic databases (Medline, Embase, PsycINFO and CENTRAL) and trial registries (ClinicalTrials.gov and the International Clinical Trials Registry Platform) from their inception to present to identify eligible RCTs. We will also check reference lists of relevant papers. The search was performed on 23 September 2020 and will be updated. We will include RCTs comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy in couples undergoing IVF. The primary outcome will be live birth resulting from the first embryo transfer. All outcomes listed in the core outcome set for infertility research will be reported. We will invite the lead investigators of eligible trials to join the In idual participant data meta-analysis of trials comparing f r o zen versus f r esh e m bryo transfer strategy (INFORM) collaboration and share the deidentified in idual participant data (IPD) of their trials. We will harmonise the IPD and perform a two-stage meta-analysis and examine treatment–covariate interactions for important baseline characteristics. The study ethics have been granted by the Monash University Human Research Ethics Committee (Project ID: 30391). The findings will be disseminated via presentations at international conferences and publication in peer-reviewed journals. CRD42021296566.
Publisher: BMJ
Date: 21-12-2010
DOI: 10.1136/BMJ.C6945
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David McLernon.