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1.  Insulin Resistance Predicts Retreatment Failure in an Efficacy Study of Peginterferon-α-2a and Ribavirin in HIV/HCV Co-infected Patients 
Journal of hepatology  2010;54(1):41-47.
Background and Aims
Few studies evaluated the efficacy of HCV re-treatment and the predictors of response in HIV/HCV co-infected patients. The role of insulin resistance as a predictor of response in this population is unknown. To evaluate safety and efficacy of pegylated interferon-α-2a and ribavirin in re-treatment of HIV/HCV co-infected patients, predictors of sustained virological response including insulin resistance, and the relationship between insulin resistance and liver histology.
This prospective, multi-centered study included HIV/HCV co-infected patients with prior interferon-based treatment failure. Patients received pegylated interferon-α-2a and ribavirin for 48 weeks. Serum HCV RNA was measured 24 weeks post treatment to assess sustained virological response. Insulin resistance was defined as HOMA-IR >2. Correlations between baseline insulin resistance and steatosis and/or cirrhosis were determined.
Sustained virological response was achieved by 14/96 (15%) patients. Of those with HOMA-IR <2, 35% (6/17) achieved sustained virological response vs 14% (15/36) of those with HOMA-IR between 2–4 and 7% (3/41) of those with HOMA-IR >4 (p=0.01). In multivariable analysis, insulin resistance and log10 HCV RNA were negatively associated with sustained virological response [AOR 0.17; 95%CI 0.05–0.64, p=0.009, and AOR 0.36; 95%CI 0.14–0.93, p=0.04, respectively). Steatosis and cirrhosis correlated with insulin resistance (p=0.02 and 0.03, respectively) but neither independently predicted sustained virological response. Discontinuations due to severe adverse events occurred in 8% and 2 patients died of unrelated cause.
In HIV/HCV co-infected patients undergoing re-treatment, sustained virological response rate is low; those without insulin resistance are significantly more likely to achieve sustained virological response.
PMCID: PMC2994950  PMID: 20974502
Insulin resistance; hepatitis C virus; chronic; HIV; retreatment; antiviral therapy; pegylated interferon alfa-2a; ribavirin
2.  Mutations in the Hepatitis C Virus Core Gene Are Associated with Advanced Liver Disease and Hepatocellular Carcinoma 
Hepatitis C virus (HCV) infection can promote the development of hepatocellular carcinoma (HCC). Published data implicate the HCV core gene in oncogenesis. We tested the hypothesis that core gene sequences from HCC patients differ from those of patients without cirrhosis/HCC.
Experimental Design
Full-length HCV sequences from HCC patients and controls were obtained from the investigators and GenBank and compared to each other. A logistic regression model was developed to predict the HCC risk of individual point mutations and other sequence features. Mutations in partial sequences (bases 36–288) from HCC patients and controls were also analyzed. The first base of the AUG start codon was designated position 1.
A logistic regression model developed through analysis of full-length core gene sequences identified seven polymorphisms significantly associated with increased HCC risk (36G/C, 209A, 271U/C, 309A/C, 435A/C, 481A, 546A/C) and an interaction term (for 209A-271U/C) that had an odds ratio < 1.0. Three of these polymorphisms could be analyzed in the partial sequences. Two of them, 36G/C and 209A, were again associated with increased HCC risk, but 271U/C, was not. The odds ratio of 209A-271U/C was not significant.
HCV core genes from patients with and without HCC differ at several positions. Of interest, 209A has been associated with interferon resistance and HCC in previous studies. Our findings suggest that HCV core gene sequence data might provide useful information about HCC risk. Prospective investigation is needed to establish the temporal relationship between the appearance of the viral mutations and development of HCC.
PMCID: PMC3142862  PMID: 19383824
HCV; HCC; core; RNA; diversity; complexity
3.  Streptococcus pneumoniae and Haemophilus influenzae type b Carriage, Central Asia 
Emerging Infectious Diseases  2005;11(9):1476-1479.
A study of children was conducted in 3 Central Asian Republics. Approximately half of the Streptococcus pneumoniae isolates were serotypes included in available vaccine formulations. Approximately 6% of children carried Haemophilus influenzae type b (Hib). Using pneumococcal and Hib conjugate vaccines may decrease illness in the Central Asian Republics.
PMCID: PMC3310603  PMID: 16229788
Streptococcus pneumoniae; Haemophilus influenzae; nasopharyngeal carriage; swab study; Central Asian Republics; Kazakhstan; Kyrgyz Republic; Uzbekistan; pneumococcal-conjugate vaccine; Hib-conjugate vaccine, dispatch
4.  Risk Factors for Pediatric Invasive Group A Streptococcal Disease 
Emerging Infectious Diseases  2005;11(7):1062-1066.
Invasive group A Streptococcus (GAS) infections can be fatal and can occur in healthy children. A case-control study identified factors associated with pediatric disease. Case-patients were identified when Streptococcus pyogenes was isolated from a normally sterile site, and matched controls (≥2) were identified by using sequential-digit dialing. All participants were noninstitutionalized surveillance-area residents <18 years of age. Conditional regression identified factors associated with invasive disease: other children living in the home (odds ratio [OR] = 16.85, p = 0.0002) and new use of nonsteroidal antiinflammatory drugs (OR = 10.64, p = 0.005) were associated with increased risk. More rooms in the home (OR = 0.67, p = 0.03) and household member(s) with runny nose (OR = 0.09, p = 0.002) were associated with decreased risk. Among children, household-level characteristics that influence exposure to GAS most affect development of invasive disease.
PMCID: PMC3371775  PMID: 16022781
case-control studies; risk factors; Streptococcus pyogenes; toxic shock syndrome; streptococcus group A; matched case-control studies; necrotizing fasciitis
5.  Drug use frequency among street-recruited heroin and cocaine users in harlem and the bronx before and after September 11, 2001 
We determined if illicit drug use frequency changes after a disaster by comparing drug use frequency in two street-recruited samples of heroin and cocaine users, ages 15–40 years. The users were interviewed between July 11 and November 11 and divided into before- and after-September 11th groups for analysis. The before and after groups were similar in the mean number of days of drug use per month (sniff cocaine 6.8 days vs. 9.4 days, respectively, P=.17; snorted heroin 13.9 vs. 14.0, respectively, P=.96; smoked crack 16.9 vs. 15.6, respectively, P=.96; and smoked marijuana 17.5 vs. 15.3, respectively, P=.36) and in the proportion of daily users: sniffed cocaine 10% versus 17%, respectively (P=.28); snorted heroin 47% versus 40%, respectively (P=.91); smoked crack 33% versus 37%, respectively (P=.68); and smoked marijuana 47% versus 40%, respectively (P=.41). Among street-recruited heroin and cocaine users in Harlem and the Bronx, the frequency of drug use did not increase following the events of September 11, 2001.
PMCID: PMC3456797  PMID: 12200509
Cross-sectional Study; Disaster; Drug Users; Illicit Drug Use; Terrorism
6.  Invasive Group A Streptococcal Disease: Risk Factors for Adults 
Emerging Infectious Diseases  2003;9(8):970-977.
We conducted a case-control study to identify risk factors for invasive group A streptococcal (GAS) infections, which can be fatal. Case-patients were identified when Streptoccus pyogenes was isolated from a normally sterile site and control subjects (two or more) were identified and matched to case-patients by using sequential-digit telephone dialing. All participants were noninstitutionalized surveillance area residents, >18 years of age. Conditional logistic regression identified the risk factors for invasive GAS infection: in adults 18 to 44 years of age, exposure to one or more children with sore throats (relative risk [RR]=4.93, p=0.02), HIV infection (RR =15.01, p=0.04), and history of injecting drug use (RR=14.71, p=0.003); in adults >45 years of age, number of persons in the home (RR=2.68, p=0.004), diabetes (RR= 2.27, p=0.03), cardiac disease (RR=3.24, p=0.006), cancer (RR= 3.54, p=0.006), and corticosteroid use (RR=5.18, p=0.03). Thus, host and environmental factors increased the risk for invasive GAS disease.
PMCID: PMC3020599  PMID: 12967496
Streptococcus pyogenes; group A streptococcal disease, invasive disease, risk factors, case-control, sequential-digit dialing; necrotizing fasciitis, streptococcal toxic shock syndrome, conditional logistic regression, research
7.  Antimicrobial Postexposure Prophylaxis for Anthrax: Adverse Events and Adherence 
Emerging Infectious Diseases  2002;8(10):1124-1132.
We collected data during postexposure antimicrobial prophylaxis campaigns and from a prophylaxis program evaluation 60 days after start of antimicrobial prophylaxis involving persons from six U.S. sites where Bacillus anthracis exposures occurred. Adverse events associated with antimicrobial prophylaxis to prevent anthrax were commonly reported, but hospitalizations and serious adverse events as defined by Food and Drug Administration criteria were rare. Overall adherence during 60 days of antimicrobial prophylaxis was poor (44%), ranging from 21% of persons exposed in the Morgan postal facility in New York City to 64% of persons exposed at the Brentwood postal facility in Washington, D.C. Adherence was highest among participants in an investigational new drug protocol to receive additional antibiotics with or without anthrax vaccine—a likely surrogate for anthrax risk perception. Adherence of <60 days was not consistently associated with adverse events.
PMCID: PMC2730317  PMID: 12396927
Anthrax; Bacillus anthracis; antimicrobial prophylaxis; adverse events; adherence
8.  New York City pharmacists' attitudes toward sale of needles/syringes to injection drug users before implementation of law expanding syringe access 
In May 2000, New York State passed legislation permitting the sale, purchase, and possession of up to 10 needles and syringes (hereafter “syringes”) without a prescription, intended to reduce blood-borne pathogen transmission among injection drug users (IDUs). To obtain baseline data on pharmacists' attitudes and practices related to human immunodeficiency virus (HIV) prevention and IDUs, a telephone survey was administered to 130 pharmacists systematically selected in New York City. Less than half of pharmacists were aware of the new law; 49.6% were willing to or supported providing nonprescription sales of syringes to IDUs. Pharmacists in support tended to be less likely to consider customer appearance “very important.” Managing and supervising pharmacists were more likely than staff pharmacists to support syringe sales to IDUs. Managing and supervising pharmacists who stocked packs of 10 syringes and personal sharps disposal containers, pharmacists who supported syringe exchange in the pharmacy, and pharmacists who were willing to sell syringes to diabetics without a prescription were more likely to support syringe sales to IDUs. Syringe disposal was a prominent concern among all pharmacists. Those not in support of syringe sales to IDUs tended to be more likely to believe the practice would increase drug use. These data suggest the need for initiatives to address concerns about syringe disposal and tailored continuing education classes for pharmacists on HIV and viral hepatitis prevention among IDUs.
PMCID: PMC3456774  PMID: 11194317

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