Determinants of suicide and accidental or violent death in the Australian HIV Observational Database.

BACKGROUND: Rates of suicide and accidental or violent death remain high in HIV-positive populations despite significantly improved prognosis since the introduction of cART. METHODS: We conducted a nested case-control study of suicide and accidental or violent death in the Australian HIV Observational Database (AHOD) between January 1999 and March 2012. For each case, 2 controls were matched by clinic, age, sex, mode of exposure and HIV-positive date to adjust for potential confounding by these covariates. Risk of suicide and accidental or violent death was estimated using conditional logistic regression. RESULTS: We included 27 cases (17 suicide and 10 violent/accidental death) and 54 controls. All cases were men who have sex with men (MSM) or MSM/ injecting drug use (IDU) mode of exposure. Increased risk was associated with unemployment (Odds Ratio (OR) 5.86, 95% CI: 1.69-20.37), living alone (OR 3.26, 95% CI: 1.06-10.07), suicidal ideation (OR 6.55, 95% CI: 1.70-25.21), and >2 psychiatric/cognitive risk factors (OR 4.99, 95% CI: 1.17-30.65). CD4 cell count of >500 cells/µL (OR 0.25, 95% CI: 0.07-0.87) and HIV-positive date ≥1990 (1990-1999 (OR 0.31, 95% CI: 0.11-0.89), post-2000 (OR 0.08, 95% CI: 0.01-0.84)) were associated with decreased risk. CD4 cell count ≥500 cells/µL remained a significant predictor of reduced risk (OR 0.15, 95% CI: 0.03-0.70) in a multivariate model adjusted for employment status, accommodation status and HIV-positive date. CONCLUSIONS: After adjustment for psychosocial factors, the immunological status of HIV-positive patients contributed to the risk of suicide and accidental or violent death. The number of psychiatric/cognitive diagnoses contributed to the level of risk but many psychosocial factors were not individually significant. These findings indicate a complex interplay of factors associated with risk of suicide and accidental or violent death.

Growth factors associated with gastric mucosal hypertrophy in autoimmune gastritis.

A prominent pathological feature of murine autoimmune gastritis is a pronounced mucosal hypertrophy. Here, we examined factors that may be responsible for inducing this hypertrophy. Because gastrin is known to be both an inducer of gastric mucosal cell proliferation and is elevated in autoimmune gastritis, mice deficient in gastrin were thymectomised at day 3 and assessed for autoimmune gastritis. Gastrin-deficient mice showed all the characteristic features of murine autoimmune gastritis, including gastric unit hypertrophy due to hyperproliferation and accumulation of immature epithelial cells, decreases in the number of zymogenic and parietal cells, and autoantibodies to the gastric H+/K+-ATPase. Hence, gastrin is not required for either the establishment of chronic gastritis or development of the typical pathological features of this disease. We also examined mRNA levels of a number of gastric mucosal growth factors in RNA samples from mice with hypertrophic autoimmune gastritis. Members of the Reg family, RegIIIbeta and RegIIIgamma, were greatly elevated in mice with hypertrophic gastritis, whereas RegI and amphiregulin (an EGF receptor ligand) were more modestly and/or inconsistently induced. These data demonstrate that induction of gastric mitogenic factors, such as members of the Reg family, can be achieved in inflammatory situations by gastrin-independent pathways. Members of the Reg family, in particular RegIIIbeta and RegIIIgamma, are good candidates to be involved in inducing the mucosal hyperproliferation in autoimmune gastritis. These findings are likely to be of relevance to other gastric inflammatory conditions.