Efficacy and safety of febuxostat for treatment of asymptomatic hyperuricemia among kidney transplant patients: A meta-analysis of observational studies.

BACKGROUND: The objective of this meta-analysis of observational studies was to evaluate the efficacy and safety profiles of febuxostat in treating hyperuricemia among kidney transplant patients. METHODS: We conducted electronic searches in PubMed, Embase, and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify studies that investigated the effects of febuxostat in kidney transplant patients on uric acid as well as safety profiles including estimated glomerular filtration rate (eGFR), hemoglobin level (Hb), white blood cell counts (WBC), liver enzymes, and trough level of tacrolimus. RESULTS: Seven observational studies with 367 participants were included in this meta-analysis. Compared with allopurinol, the febuxostat group demonstrated a higher odds of achieving target uric acid levels lower than 6 mg/dL within 12 months (OR = 2.9, P = .004). However, there was no statistical difference in change of uric acid (WMD = -1.0 mg/dL/y, P = .32) and change in allograft eGFR within a year (WMD = 0.01 mL/min/1.73 m2 /y, P = .98) between febuxostat and allopurinol. Regarding safety profiles, there were no statistical differences in eGFR, Hb, WBC, liver enzymes (AST, ALT), and trough level of tacrolimus between baseline and at the study end. Only one study reported suspected graft loss among febuxostat group. CONCLUSION: Among kidney transplant patients, treating hyperuricemia with febuxostat showed a higher odds of reaching the target of serum uric acid < 6 mg/dL compared with allopurinol without causing significant side effects including change in tacrolimus level, liver function, decline in renal graft function, and bone marrow function.

Marijuana use in the immediate 5-year premorbid period is associated with increased risk of onset of schizophrenia and related psychotic disorders.

OBJECTIVES: Several studies suggest that adolescent marijuana use predicts earlier age at onset of schizophrenia, which is a crucial prognostic indicator. Yet, many investigations have not adequately established a clear temporal relationship between the use and onset. METHODS: We enrolled 247 first-episode psychosis patients from six psychiatric units and collected data on lifetime marijuana/alcohol/tobacco use, and ages at onset of prodrome and psychosis in 210 of these patients. Cox regression (survival analysis) was employed to quantify hazard ratios (HRs) for effects of diverse premorbid use variables on psychosis onset. RESULTS: Escalation of premorbid use in the 5years prior to onset was highly predictive of an increased risk for onset (e.g., increasing from no use to daily use, HR=3.6, p<0.0005). Through the analysis of time-specific measures, we determined that daily use approximately doubled the rate of onset (HR=2.2, p<0.0005), even after controlling for simultaneous alcohol/tobacco use. Building on previous studies, we were able to determine that cumulative marijuana exposure was associated with an increased rate of onset of psychosis (p=0.007), independent of gender and family history, and this is possibly the reason for age at initiation of marijuana use also being associated with rate of onset in this cohort. CONCLUSIONS: These data provide evidence of a clear temporal relationship between escalations in use in the five years pre-onset and an increased rate of onset, demonstrate that the strength of the association is similar pre- and post-onset of prodromal symptoms, and determine that early adult use may be just as important as adolescent use in these associations.