Among Vancouver participants there was an apparent downward trend in the proportion of participants reporting recent homelessness across follow-up visits.The distribution of stabilized IPTWs was narrow at each follow-up visit in both settings, ranging from 0.65 to 1.40 in Tijuana and from 0.38 to 2.75 in Vancouver, respectively. Fig. 1 plots the distribution of log-transformed stabilized weights across follow-up visits for Tijuana and Vancouver. Given that, for each site-specific IPTW distribution, the mean untransformed weight over follow-up is approximately 1 , the interquartile ranges are relatively balanced, and the minimum and maximum weight values are not too extreme, we were satisfied with the estimated weights and did not alter them further prior to analysis. Based on our inverse-probability-of-treatment-weighted estimates – which are conditional on participants’ baseline age, gender, and their origin cohort – we found that recent homelessness was associated with increased odds of having recently assisted an IDU initiation event among PWID in Tijuana and Vancouver . In Tijuana , recent homelessness was associated with 66% greater odds of having provided IDU initiation assistance over the same six-month period. In Vancouver , recent homelessness was associated with 47% greater odds of having provided IDU initiation assistance over the same six-month period. Results of our sensitivity analyses indicate that, in both Tijuana and Vancouver, the weighting and adjustment procedures applied in this study attenuated the observed effect of recent homelessness on recently assisting IDU initiation. This is the first quantitative study to assess the longitudinal relationship between recent homelessness and assisting others in initiating IDU, while accounting for potential time varying confounders through inverse-probability-of-treatment weights. Based on 2619 visits made by 703 PWID in Tijuana over three years,vertical farming equipment we found that recent homelessness was associated with 66% greater odds of having provided IDU initiation assistance over the same six-month period.
Based on 5617 visits made by 1551 PWID in Vancouver, we found that recent homelessness was associated with 47% greater odds of having provided IDU initiation assistance over the same six-month period. Given the concentrated intersection of homelessness and IDU in North America, this study adds insight into the potential influence of housing on IDU initiation. Prior literature has indicated that experiencing homelessness may, for injection-naïve individuals, increase the risk of initiating IDU or, for former PWID, increase the risk of reinstating IDU – taken together with our results, these findings indicate that interventions aimed broadly at addressing homelessness, such as Housing First models , have the potential to reduce IDU and related harms via multiple pathways. Our findings in Vancouver are consistent with previous research exploring the dynamics of housing and IDU in the region. The Downtown Eastside of Vancouver, in particular, is an area with a high concentration of both homelessness and public IDU . Chami et al. found that, among a cohort of street-involved youth, that those living in the Downtown Eastside were more than twice as likely to initiate IDU compared to those living elsewhere. Further, findings from DeBeck et al. indicate that, throughout Vancouver, those experiencing homelessness are almost seven times as likely to report IDU in public spaces than those not experiencing homelessness. This high visibility and the high density of PWID in the Downtown Eastside may provide injection-naïve individuals ready access to those with knowledge about IDU practices and thereby make PWID who inject in public more likely to be recipients of injection initiation assistance requests. Given the high concentration of homelessness and public injection in the Downtown Eastside , these findings add an additional dimension to our understanding of this drug using context, particularly with respect to how the endemic homelessness experienced by many of its drug-using residents may be contributing to an expansion of IDU practices across injection-naïve individuals vulnerable to drug use transitions.
The context of IDU and homelessness in Tijuana, though, is substantially different than that of Vancouver. In particular, the over-policing of PWID experiencing homelessness may play a more determinative role in shaping IDU trajectories compared to housing status. It is noteworthy that a previous pooled analysis undertaken by our group, which included data from the same cohorts as the present study, found that a higher frequency of police interactions was associated with a higher odds of assisting IDU initiation . What this study also found, though, was that in Tijuana 71% of police interactions were arrests and detainments, whereas in Vancouver only 24% were arrests and detainments with 63% described as “neutral interactions” – indicating a more severe impact of policing on PWID in Tijuana than in Vancouver. It is likely that policing also plays a differential role for PWID experiencing homelessness in each of these settings. The over-reliance on policing in Tijuana is highlighted by the Tijuana Mejora program in which, from December 2014 to March 2015, law enforcement detained approximately 1000 people, most of whom were PWID, living along the Tijuana River Channel and forced many of them into unregulated, involuntary drug treatment programs . This indicates a potential mediating pathway, in which both IDU and homelessness in Tijuana increase exposure to policing, and that this exposure to policing then results in an array of harms. It is important that future research into the phenomenon of IDU initiation assistance be designed to capture and evaluate the validity of such mediating pathways in order to better characterize the role that experiencing homelessness may play in providing IDU initiation assistance across heterogeneous geographic settings. The provision of injection initiation assistance is a highly stigmatized behavior among PWID and, as stated in prior PRIMER studies, our outcome measure is likely prone to underreporting, which may have contributed in part to the low observed frequency of injection initiation assistance in our study . Non-probability sampling methods were used in both Tijuana and Vancouver to recruit participants, meaning our findings may not be generalizable to other populations and settings. While this study leveraged the longitudinal nature of the data, we modelled contemporaneous measures of recent homelessness and recent IDU injection initiation, i.e., both reflect behaviors over the same six-month period.
Correspondingly, it is possible that the observed association may be driven, in part, by the outcome causing the exposure . Despite reverse causality as an alternative explanation for our main findings, we elected to lag the covariate measures for a given visit to ensure that potential confounder values always preceded both exposure and outcome measures; if we had lagged both exposure and covariate values instead—to alleviate concerns of reverse causality—it is possible that some covariates, now contemporaneously measured with the exposure, might be acting as mediators versus as confounders, resulting in an effect estimate closer to the null. We observed a decline in the proportion of participants reporting recent homelessness across follow-up visit for Vancouver, which may indicate that participants experiencing homelessness were more likely to be lost to follow-up over time than those not experiencing homelessness. We note as well that research indicating more severe law enforcement exposure among people experiencing homelessness in Tijuana may have resulted in challenges in recruiting and following-up with participants experiencing homelessness due to higher rates of incarceration . Given that our homelessness exposure was operationalized differently in each setting, it is not immediately clear if the findings across settings are readily comparable. Finally, while estimates indicate that 40%–61% of PWID in North America experience homelessness each year,4×4 grow tray the proportion of participants in our study who reported an experience of homelessness in the past six months was substantially lower. This is likely due to the challenges of recruiting and retaining individuals experiencing more severe homelessness. If severity of homelessness is inversely related to selection into our study and also directly related to risk of providing injection initiation assistance, then our findings likely underestimate the relationship between severe homelessness and assisting in IDU initiation events among PWID. Δ 9 -tetrahydrocannabinol , the primary cannabinoid responsible for the psychotropic and biologic activities of marijuana , mediates its effects on the immune system by interacting with cannabinoid receptor type II . Although few immunologic studies have been carried out in active MJ smokers , we have documented that alveolar macrophages recovered from the lungs of habitual MS exhibit alterations in phagocytosis, bacterial killing and cytokine production . Using a variety of in vitro models and animal exposure studies, THC has also been shown to suppress the function of lymphocytes and dendritic cells , skew their cytokine production , promote the generation of myeloid suppressor cells , and prevent effective host responses to infections and tumors . A few epidemiologic studies have identified MJ use as a potential risk factor for opportunistic infections and progression from HIV to AIDS . However, when short-term MJ use was studied prospectively in a cohort of HIV-positive subjects it had no impact on systemic viral load, cytokine production or CD4 counts . Given the potent immuno suppressive properties of cannabinoids that have been observed in model systems and the potential implications for public health, the current study was designed to assess whether habitual MJ smoking has a similar adverse effect on adaptive humoral and cellular immune responses to a viral challenge. Matched cohorts of otherwise healthy non-smokers and chronic MS, who were naive to Hepatitis B virus , were prospectively recruited to receive a standard series of three Hepatitis B vaccinations.
HBV is a serious pathogen and vaccine responses to hepatitis B surface antigen are directly dependent upon the function of DC, T cells and B cells . As such, by examining the generation of adaptive immune responses to HBsAg, the intent was to carry out a realistic assessment of the potential impact of longterm MJ smoking on human immunity and adaptive host defenses. Peripheral blood was obtained from healthy volunteers with written informed consent and procedures approved by the UCLA Institutional Review Board. Peripheral blood mononuclear cells were isolated by ficoll density centrifugation. Monocyte-derived DC were generated by culturing adherent PBMC in X-VIVO 15 medium supplemented with GM-CSF and IL-4 according to a standard protocol . THC Drug Supply Program, Bethesda, MD) was added at the initiation of DC cultures at 500 ng/ml while control DC cultures received diluent alone . After 6 days, DC were purified by negative selection as previously described and cultured overnight with/without 40 μg/ml of hepatitis B surface antigen protein . Autologous CD3+ T cells were purified by negative selection and labeled with carboxyfluorescein succinimidyl ester to monitor proliferation in response to HBsAg-loaded DC that had been exposed in vitro to THC or diluent alone . Following 5 days of co-culture, non-adherent cells were recovered and analyzed by flow cytometry . Associated culture supernatants were evaluated for pre-selected cytokines by SearchLight® immunoassay .Interested volunteers provided written informed consent and all procedures were approved by the UCLA Institutional Review Board. Both men and women, 21 to 54 years of age, were eligible if they had never received prior HBV vaccination and met the criteria for either a NS or MS. Marijuana smokers were defined by a lifetime history of >10 joint-yrs of MJ smoking and current use of at least 5 joints/wk. Subjects with a history of routine tobacco or non-MJ substance abuse at any time in the past, or any use of such substances within the past 2 yrs were excluded. Non-smokers were defined as those with no history of tobacco, cocaine, MJ or other substance abuse on a regular basis and no use at all within the last 5 years. Any subject that had abused intravenous drugs or inhaled cocaine or methamphetamine was excluded. Urine drug screening was performed in addition to a detailed drug history questionnaire. Participants were also screened to exclude chronic illnesses that might impair vaccine responses or increase risks from smoking including chronic lung disease; active cardiac or vascular disease; kidney disease; seizures or significant psychiatric disorder; collagen-vascular disease, diabetes mellitus, cancer or HIV. Use of immunosuppressive medications within the past 30 days was excluded . A screening serum HBsAb titer was performed on all subjects to exclude those with evidence of pre-existing immunity to HBV . In addition, female subjects of child-bearing age who were pregnant, lactating or not using approved contraception were not allowed to participate.