| 2. |
- Lang, Angelica E., et al.
(författare)
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A randomized controlled trial investigating effects of an individualized pedometer driven walking program on chronic low back pain
- 2021
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Nature. - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Walking is an easily prescribed physical activity for people with low back pain (LBP). However, the evidence for its effectiveness to improve pain and disability levels for people with chronic low back pain (CLBP) within a community setting has not been evaluated. This study evaluates the effectiveness of a clinician guided, pedometer-driven, walking intervention for increasing physical activity and improving clinical outcomes compared to education and advice. Methods: Randomized controlled trial recruiting N = 174 adults with CLBP. Participants were randomly allocated into either a standardized care group (SG) or pedometer based walking group (WG) using minimization allocation with a 2:1 ratio to the WG. Prior to randomization all participants were given a standard package of education and advice regarding self-management and the benefits of staying active. Following randomization the WG undertook a physiotherapist guided pedometer-driven walking program for 12 weeks. This was individually tailored by weekly negotiation of daily step targets. Main outcome was the Oswestry Disability Index (ODI) recorded at baseline, 12 weeks, 6 and 12 months. Other outcomes included, numeric pain rating, International Physical Activity Questionnaire (IPAQ), Fear-Avoidance Beliefs Questionnaire (FABQ), Back Beliefs questionnaire (BBQ), Physical Activity Self-efficacy Scale, and EQ-5D-5L quality of life estimate. Results: N = 138 (79%) participants completed all outcome measures at 12 weeks reducing to N = 96 (55%) at 12 months. Both observed and intention to treat analysis did not show any statistically significant difference in ODI change score between the WG and the SG at all post-intervention time points. There were also no significant between group differences for change scores in all secondary outcome measures. Post hoc sensitivity analyses revealed moderately disabled participants (baseline ODI >= 21.0) demonstrated a greater reduction in mean ODI scores at 12 months in the WG compared to SG, while WG participants with a daily baseline step count < 7500 steps demonstrated a greater reduction in mean ODI scores at 12 weeks. Conclusions: Overall, we found no significant difference in change of levels of (ODI) disability between the SG and WG following the walking intervention. However, ODI responses to a walking program for those with moderate levels of baseline disability and those with low baseline step count offer a potential future focus for continued research into the benefit of walking as a management strategy for chronic LBP. Trial registration: United States National Institutes of Health Clinical Trails registry (http://ClinicalTrials.gov/) No. NCT02284958 (27/10/2014).
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| 3. |
- Licciardello, Marco P., et al.
(författare)
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A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor
- 2017
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 13:7, s. 771-778
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Tidskriftsartikel (refereegranskat)abstract
- Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for gamma-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.
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