The state of science on including inhalation within supervised consumption services: A scoping review of academic and grey literature.

BACKGROUND: Internationally, many supervised consumption services (SCS) include drug inhalation (smoking). However, most research is focused on SCS for people who inject drugs. We aimed to: (1) synthesize the literature on including inhalation or other forms of non-injection drug use (e.g., oral, intranasal) within SCS; (2) describe the state of the science on the feasibility of this practice and its outcomes; and (3) outline an agenda for future evaluation research in this area. METHODS: We searched 9 academic and 13 grey literature databases and ultimately included 40 studies. Thirty-two studies (80%) reported findings from feasibility or needs assessments. From these studies, we extracted information on willingness to use these services, perspectives of people who use drugs and other stakeholders, and recommendations for implementation. Eight studies (20%) evaluated including inhalation in SCS, from which we extracted data on associated outcomes. Data were analysed using narrative synthesis and descriptive statistics. RESULTS: We found high willingness to use SCS including inhalation among people who use drugs, especially those experiencing structural vulnerability. Research emphasized a need for implementation to account for the social nature of drug inhalation, and to limit potential occupational hazards associated with passive inhalation. Positive outcomes associated with inhalation within SCS included improved health and safety of people who use drugs and decreased public drug use. However, this evidence was based primarily on a limited number of studies with designs of mixed quality. CONCLUSION: Our review demonstrates feasibility of, and need for, implementing SCS including inhalation, and some potential positive outcomes associated with this practice. However, more comprehensive and systematic evaluations of including inhalation as well as other forms of non-injection drug use (e.g., oral, intranasal, rectal) within SCS should be conducted.

To what extent do supervised drug consumption services incorporate non-injection routes of administration? A systematic scoping review documenting existing facilities.

BACKGROUND: Most of the existing research on supervised consumption services (SCS) is focused on injection drug use. Less is known about the applicability of SCS for people who consume drugs orally, intranasally, or through inhalation. This is problematic because people who use drugs through modes other than injection are also at risk of overdose death and other harm, and experience barriers accessing health and social services. We aimed to describe existing SCS models that accommodate these alternate routes of drug consumption, and synthesize available information on characteristics of program participants. METHODS: We conducted a systematic scoping review of 9 peer-reviewed and 13 grey literature databases on SCS that incorporate non-injection routes of consumption. We screened 22,882 titles, and excluded 22,843 (99.8%) articles. We ultimately included 39 (0.2%) full-text articles; 28 (72%) of these articles explicitly identified SCS that permit alternate routes of consumption and 21 (54%) discussed characteristics of participants who consume drugs through non-injection routes. Data on study characteristics, terms and definitions, and site and program participant characteristics were extracted and double-coded. Extracted data were analyzed using descriptive statistics and narrative synthesis. RESULTS: Included articles describe 48 SCS that permit non-injection routes of consumption, most of which were located in Germany. The majority of these SCS were legally sanctioned and had models of care that were largely comparable to supervised injection services. Notable differences included physical infrastructure such as ventilated rooms or outdoor areas to accommodate inhalation, and shorter time limits on non-injection drug consumption episodes. Program participants engaging in non-injection forms of consumption were typically men over the age of 30 and structurally vulnerable (e.g., experiencing homelessness or unstable housing). CONCLUSIONS: Extant academic and grey literature indicates that site characteristics and demographics of program participants of SCS that permit non-injection routes of consumption largely reflect those of supervised injection services. Further research on the range of existing SCS that incorporate non-injection routes of consumption is needed to ensure high quality service provision, and improved health outcomes for people who consume drugs via oral, intranasal, and inhalation routes.

Matrix metalloproteinase-2 in oncostatin M-induced sarcomere degeneration in cardiomyocytes.

Cardiomyocyte dedifferentiation may be an important source of proliferating cardiomyocytes facilitating cardiac repair. Cardiomyocyte dedifferentiation and proliferation induced by oncostatin-M (OSM) is characterized by sarcomere degeneration. However, the mechanism underlying sarcomere degeneration remains unclear. We hypothesized that this process may involve matrix metalloproteinase-2 (MMP-2), a key protease localized at the sarcomere in cardiomyocytes. We tested the hypothesis that MMP-2 is involved in the sarcomere degeneration that characterizes cardiomyocyte dedifferentiation. Confocal immunofluorescence and biochemical methods were used to explore the role of MMP-2 in OSM-induced dedifferentiation of neonatal rat ventricular myocytes (NRVM). OSM caused a concentration- and time-dependent loss of sarcomeric α-actinin and troponin-I in NRVM. Upon OSM-treatment, the mature sarcomere transformed to a phenotype resembling a less-developed sarcomere, i.e., loss of sarcomeric proteins and Z-disk transformed into disconnected Z bodies, characteristic of immature myofibrils. OSM dose dependently increased MMP-2 activity. Both the pan-MMP inhibitor GM6001 and the selective MMP-2 inhibitor ARP 100 prevented sarcomere degeneration induced by OSM treatment. OSM also induced NRVM cell cycling and increased methyl-thiazolyl-tetrazolium (MTT) staining, preventable by MMP inhibition. These results suggest that MMP-2 mediates sarcomere degeneration in OSM-induced cardiomyocyte dedifferentiation and thus potentially contributes to cardiomyocyte regeneration.