16 research outputs found

    The effect of teriparatide treatment on circulating periostin and its relationship to regulators of bone formation and BMD in postmenopausal women with osteoporosis

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    Context: Treatment of postmenopausal osteoporosis with teriparatide (PTH 1-34) increases bone formation and improves bone microarchitecture. A possible modulator of this mechanism of action is periostin. In vitro experiments have shown that periostin may regulate osteoblast differentiation and bone formation through Wnt signaling. Periostin secretion is increased by PTH in preclinical models, but the effect of teriparatide treatment of postmenopausal osteoporosis on periostin is not currently known. Objectives, to: i) determine the effect of teriparatide treatment on circulating levels of periostin and other regulators of bone formation and ii) investigate how changes in periostin relate to changes in bone turnover markers, regulators of bone formation and bone mineral density. Participants and design: 20 women with postmenopausal osteoporosis, a two-year open-label single-arm study. Intervention: Teriparatide 20 mcg was administered by subcutaneous injection daily over 104 weeks. Periostin, sclerostin and DKK-1, PINP and CTX were measured in fasting serum collected at baseline (two visits) then at weeks 1,2,4,12,26,52,78 and 104. BMD was measured at the lumbar spine, total hip and femoral neck by DXA. Results: Periostin levels increased by 6.6% (95% CI -0.4, 13.5) after 26 weeks teriparatide treatment and significantly by 12.5% (95% CI 3.3,21.0, P<0.01) after 52 weeks. Change in periostin was positively correlated with change in lumbar spine BMD at week 52 (r=0.567(95% CI 0.137,0.817), P<0.05) and femoral neck BMD at week 104(r=0.682(95% CI 0.261,0.885), P<0.01). Conclusion: Teriparatide therapy increases periostin secretion; it is unclear whether this increase mediates the effect of the drug on bone

    Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry

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    Genomic reconstruction of the SARS-CoV-2 epidemic in England.

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    The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021

    Brief Report: Using the Internet to Identify Persons with Cognitive Impairment for Participation in Clinical Trials

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    Identifying, recruiting, and enrolling persons in clinical trials of dementia treatments is extremely difficult. One approach to first-wave screening of potential participants is the use of online assessment tools. Initial studies using the Dementia Risk Assessment (DRA)—which includes a previously validated recognition memory test—support the use of this self-administered assessment to identify individuals with “suspected MCI” or “suspected dementia.” In this study, we identified between 71 and 622 persons with suspected dementia and between 128 and 1653 persons with suspected mild cognitive impairment (depending on specific criteria) over the course of 22 months. Assessment tools that can inexpensively and easily identify individuals with higher than average risk for cognitive impairment can facilitate recruitment for large-scale clinical trials for dementia treatments
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