high rates of ER use were observed among IDUs, despite high rates of primary care use among this same population. ER use was due primarily to preventable injection-related complications that are less amenable to primary care interventions, and therefore educational and prevention efforts that encourage and enable sterile injection practices should be promoted.

Despite the availability of effective therapy for hepatitis C virus (HCV) infection, there are little data on the uptake of treatment. We evaluated factors associated with HCV infection and the uptake of HCV treatment in a large community-based inner city cohort in Vancouver, Canada. The Community Health and Safety Evaluation is a cohort study of inner city residents recruited from January 2003 to June 2004. HIV and HCV status and information on prescriptions for HCV treatment were determined through linkage with provincial databases. HCV prevalence was calculated and factors associated with HCV infection were identified. HCV treatment uptake and incidence of HCV infection from January 2000 to December 2004 were expressed in terms of person-years of observation. Among 2913 individuals, HCV antibody testing was performed in 2118 and the HCV seroprevalence was 64.2% (1360 of 2118). In total, 1.1% of HCV antibody-positive individuals (15 of 1360) initiated treatment for HCV infection from January 2000 to December 2004 [0.28 cases per 100 person-years (95% CI, 0.15-0.46)]. Three of 15 (20.0%) treated individuals achieved a sustained virological response. During the same period, the incidence of HCV infection was 7.26 cases (95% CI, 5.72-8.80) per 100 person-years. Overall, the rate of new HCV seroconversions in this cohort in the study period was about 25 times the rate of HCV treatment uptake. There are extremely low rates of HCV treatment initiation and very limited effectiveness, despite a high prevalence of HCV infection in this large community-based cohort of inner city residents with access to universal healthcare.

BackgroundMyelinating Schwann cells (mSCs) form myelin in the peripheral nervous system. Because of the works by us and others, matrix metalloproteinase-9 (MMP-9) has recently emerged as an essential component of the Schwann cell signaling network during sciatic nerve regeneration.Methodology/Principal FindingsIn the present study, using the genome-wide transcriptional profiling of normal and injured sciatic nerves in mice followed by extensive bioinformatics analyses of the data, we determined that an endogenous, specific MMP-9 inhibitor [tissue inhibitor of metalloproteinases (TIMP)-1] was a top up-regulated gene in the injured nerve. MMP-9 capture followed by gelatin zymography and Western blotting of the isolated samples revealed the presence of the MMP-9/TIMP-1 heterodimers and the activated MMP-9 enzyme in the injured nerve within the first 24 h post-injury. MMP-9 and TIMP-1 co-localized in mSCs. Knockout of the MMP-9 gene in mice resulted in elevated numbers of de-differentiated/immature mSCs in the damaged nerve. Our comparative studies using MMP-9 knockout and wild-type mice documented an aberrantly enhanced proliferative activity and, accordingly, an increased number of post-mitotic Schwann cells, short internodes and additional nodal abnormalities in remyelinated nerves of MMP-9 knockout mice. These data imply that during the first days post-injury MMP-9 exhibits a functionally important anti-mitogenic activity in the wild-type mice. Pharmacological inhibition of MMP activity suppressed the expression of Nav1.7/1.8 channels in the crushed nerves.Conclusion/SignificanceCollectively, our data established an essential role of the MMP-9/TIMP-1 axis in guiding the mSC differentiation and the molecular assembly of myelin domains in the course of the nerve repair process. Our findings of the MMP-dependent regulation of Nav channels, which we document here for the first time, provide a basis for therapeutic intervention in sensorimotor pathologies and pain.

Spontaneous clearance of hepatitis C (HCV) may provide protection against reinfection. In a large community-based cohort study of 3,553 inner-city residents (mainly injection drug users), we identified HCV-infected individuals in whom virological clearance had occurred and compared the rate of reinfection in this group with that observed in previously uninfected members of the same cohort. We identified 926 HCV-uninfected and 658 HCV-infected viremic subjects at baseline, with 152 of 658 (23.1%) spontaneously clearing viremia over a median follow-up of 5.2 years (IQR, 2.8-7.4). At baseline, individuals with HCV clearance were more likely to be HIV coinfected (P < .001) and to be engaged in frequent illicit drug use (P ‫؍‬ .004) and injection drug use (P < .001). The occurrence of HCV infection was lower in individuals with previous infection (14/152, 9.2%) compared with that in those without previous infection (172/926, 18.6%), with incidence rates of 1.8 (95% CI, 0.9-3.0 cases/100 person-years) and 8.1 (95% CI, 6.9-9.4 cases/100 person-years) cases/100 person-years, respectively, after accounting for follow-up. H epatitis C virus (HCV) infection constitutes a major public health burden, affecting more than 170 million individuals throughout the world. 1 Injection drug use has emerged as the primary mode of transmission globally, accounting for more than 75% of incident cases. 1 The prevalence of HCV infection in injection drug users (IDUs) is 60%-90%, 2-4 with 80% of these individuals going on to develop persistent, chronic infection. 5 Pharmacologic advances have led to the development of effective treatment regimens leading to a virological "cure" in 50% of HCV-infected subjects receiving pegylated interferon in combination with ribavirin. 6,7 Although these outcomes have been replicated in active IDUs, 8,9 there is still concern that the risk of HCV reinfection through recurrent parenteral exposure will negate the benefits of treatment.In fact, reinfection with HCV after spontaneous clearance has been demonstrated to occur in IDUs with ongoing risk behavior, 10,11 as well as in other groups, including polytransfused children with thalassemia 12 and subjects undergoing liver transplantation. 13 Reinfection does occur in chimpanzees rechallenged with HCV after clearance of the original infection, 14-17 but the resistance to subsequent HCV infection is relatively greater, which is likely related to immune protection. 14,18 In humans, preliminary data from one cohort suggested that IDUs who successfully clear HCV are less likely to develop viremia following reexposure to HCV than are previously uninfected individuals. 19 Given that a greater proportion of IDUs are receiving treatment for HCV, a clearer understanding of this protection from reinfection and its determinants is important. With this in mind, we compared the rate of HCV reinfection among individuals who had

Aboriginal ethnicity and female sex were associated with increased rates of HCV clearance, while HIV coinfection and illicit drug use were associated with increased HCV persistence.

T h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 354;23 www.nejm.org june 8, 2006 2512 stances after a disaster, the heavy workload, panic, and incomplete patient records. 1 However, despite these drawbacks, crush injuries after the Marmara earthquake, in Turkey, which formed the main basis for our article, were documented in as much detail as possible regarding the fate of the injured persons, their profile, and any nephrologic problems, thanks to the high rate of response to questionnaires that were sent to the reference hospitals immediately after the disaster. This high response rate made it possible to understand the sequence of events after disasters of great magnitude and helped us develop logistic coordination, as presented in the article.We also agree that rapid evacuation of the victims is important. As we noted in our article, "after a disaster, rapid transport systems should be devised, if feasible, to evacuate injured persons from the epicenter."Kettler is correct that the hyperkalemic response to succinylcholine was not mentioned in our article, but it was not our aim to provide a detailed technical description of how to treat persons with crush-related injuries. The primary focus of our article was to provide conceptual information about lifesaving aspects of the medical care that is related to renal rescue, as well as the global and local logistics that are needed to support such action. Hence, owing to space limitations, it was impossible to include all details about the many key interventions required in disaster conditions; this information can be found elsewhere. 2,3 However, we thank Kettler for emphasizing the importance of hyperkalemia in patients with crush injuries. In one of our articles on the Marmara earthquake, we reported that the risk of fatal hyperkalemia continues even after hospitalization and that early detection and treatment of hyperkalemia may improve the final outcome of disaster victims with renal damage. 4Mehmet Sukru Sever, M.D.

No abstract

HCV treatment uptake remains low in this large community-based cohort of inner city residents with a high HCV prevalence and access to universal healthcare.