Effect of Stem Cell Injections on Osteoarthritis-related Structural Outcomes: A Systematic Review.

OBJECTIVE: To systematically review the evidence for the efficacy of mesenchymal stem cell (MSC) injections in improving osteoarthritis (OA)-related structural outcomes. METHODS: Ovid Medline and EMBASE were searched from their inceptions to April 2020 using MeSH terms and key words. Independent reviewers extracted data and assessed methodological quality. Qualitative evidence synthesis was performed due to the heterogeneity of interventions and outcome measures. RESULTS: Thirteen randomized controlled trials (phase I or II) were identified: 10 in OA populations and 3 in populations at risk of OA, with low (n = 9), moderate (n = 3), or high (n = 1) risk of bias. Seven studies used allogeneic MSCs (4 bone marrow, 1 umbilical cord, 1 placenta, 1 adipose tissue), 6 studies used autologous MSCs (3 adipose tissue, 2 bone marrow, 1 peripheral blood). Among the 11 studies examining cartilage outcomes, 10 found a benefit of MSCs on cartilage volume, morphology, quality, regeneration, and repair, assessed by magnetic resonance imaging, arthroscopy, or histology. The evidence for subchondral bone was consistent in all 3 studies in populations at risk of OA, showing beneficial effects. Sixteen unpublished, eligible trials were identified by searching trial registries, including 8 with actual or estimated completion dates before 2016. CONCLUSION: Our systematic review of early-phase clinical trials demonstrated consistent evidence of a beneficial effect of intraarticular MSC injections on articular cartilage and subchondral bone. Due to the heterogeneity of MSCs, modest sample sizes, methodological limitations, and potential for publication bias, further work is needed before this therapy is recommended in the management of OA.

Trends in the sequence of first alcohol, cannabis and cigarette use in Australia, 2001-2016.

BACKGROUND: Recent analyses of data from the US found that young people were increasingly engaging in cannabis use before alcohol and cigarettes. These shifts are important for public health, but it is not clear whether such trends extend beyond the US. The aim of this study is to examine whether and how the age and sequencing of initiation into alcohol, cannabis and cigarette use has changed in Australia since the early 2000s. METHODS: Data came from six waves of the Australian National Drug Strategy Household Survey, spanning 2001-2016. We used data from 18 to 21 year-olds (n = 6849) and examined trends in the age at first use for each of the three substances plus any changes in the order of initiation. RESULTS: The mean age of initiation increased steadily for all three substances (e.g. from 14.9 in 2001 to 16.4 in 2016 for alcohol), while the prevalence of any use declined. There were some changes in ordering of use. For example, in 2001, 62 % of respondents who used both cigarettes and cannabis had first used cigarettes at an earlier age than cannabis, compared with 41 % in 2016. Young people who used both alcohol and cannabis remained more likely to try alcohol before cannabis across the study period. CONCLUSIONS: Our results partly replicated US findings, with differences potentially reflecting the substantially different environment around these substances in the US compared to Australia. The age of initiation for alcohol, cigarette and cannabis use in Australia has increased sharply over the past 15 years.