ABSTRACT
CONTEXT: The dramatic rise in the use of prescription opioids to treat non-cancer pain has been paralleled by increasing prescription opioid abuse. However, detailed analyses of these trends and programs to address them are lacking. OBJECTIVE: To study the association between state shipments of prescription opioids for medical use and prescription opioid abuse admissions and to assess the effects of state prescription drug monitoring programs (PDMPs) on prescription opioid abuse admissions. DESIGN AND SETTING: A RETROSPECTIVE ECOLOGICAL COHORT STUDY COMPARING STATE PRESCRIPTION OPIOID SHIPMENTS (SOURCE: Automation of Reports and Consolidated Orders Systems database) and inpatient admissions for prescription opioid abuse (source: Treatment Episode Data Set) in 14 states with PDMPs (intervention group) and 36 states without PDMPs (control group) for the period 1997-2003. RESULTS: From 1997 to 2003, oxycodone, morphine, and hydrocodone shipments increased by 479%, 100%, and 148% respectively. Increasing prescription oxycodone shipments were significantly associated with increasing prescription opioid admission rates (p < 0.001). PDMP states had significantly lower oxycodone shipments than the control group. PDMP states had less increase in prescription opioid admissions per year (p = 0.063). A patient admitted to an inpatient drug abuse rehabilitation program in a PDMP state was less likely to be admitted for prescription opioid drug abuse (Odds ratio = 0.775, 95% Confidence Interval 0.764-0.785). CONCLUSIONS: PDMPs appear to decrease the quantity of oxycodone shipments and the prescription opioid admission rate for states with these programs. Overall, opioid shipments rose significantly in PDMP states during the study period indicating a negligible "chilling effect" on physician prescribing.
ABSTRACT
Infection by human hepatitis C virus (HCV) is the principal cause of post-transfusion hepatitis and chronic liver diseases worldwide. A reliable in vitro culture system for the isolation and analysis of this virus is not currently available, and, as a consequence, HCV pathogenesis is poorly understood. We report here the first robust in vitro system for the isolation and propagation of HCV from infected donor blood. This system involves infecting freshly prepared macrophages with HCV and then transmission of macrophage-adapted virus into freshly immortalized B-cells from human fetal cord blood. Using this system, newly isolated HCV have been replicated in vitro in continuous cultures for over 130 weeks. These isolates were also transmitted by cell-free methods into different cell types, including B-cells, T-cells and neuronal precursor cells. These secondarily infected cells also produced in vitro transmissible infectious virus. Replication of HCV-RNA was validated by RT-PCR analysis and by in situ hybridization. Although nucleic acid sequencing of the HCV isolate reported here indicates that the isolate is probably of type 1a, other HCV types have also been isolated using this system. Western blot analysis shows the synthesis of major HCV structural proteins. We present here, for the first time, a method for productively growing HCV in vitro for prolonged periods of time. This method allows studies related to understanding the replication process, viral pathogenesis, and the development of anti-HCV drugs and vaccines.