Routine screening for hepatitis C in pregnancy is cost-effective in a large urban population in Ireland: a retrospective study.

OBJECTIVE: To investigate whether risk factor-based screening in pregnancy is failing to identify women with hepatitis C virus (HCV) infection and to assess the cost-effectiveness of universal screening. DESIGN: Retrospective study and model-based economic evaluation. SETTING: Two urban tertiary referral maternity units, currently using risk factor-based screening for HCV infection. POPULATION: Pregnant women who had been tested for hepatitis B, HIV but not HCV. METHODS: Anonymised sera were tested for HCV antibody. Positive sera were tested for HCV antigen. A cost-effectiveness analysis of a change to universal screening was performed using a Markov model to simulate disease progression and Monte Carlo simulations for probabilistic sensitivity analysis. MAIN OUTCOME MEASURES: Presence of HCV antigen and cost per quality-adjusted life year (QALY). RESULTS: In all, 4655 samples were analysed. Twenty had HCV antibodies and five HCV antigen. This gives an active infection rate of 5/4655, or 0.11%, compared with a rate of 0.15% in the risk-factor group. This prevalence is 65% lower than a previous study in the same hospitals from 2001 to 2005. The calculated incremental cost-effectiveness ratio (ICER) for universal screening was €3,315 per QALY gained. CONCLUSION: This study showed that the prevalence of HCV infection in pregnant women in the Dublin region has declined by 65% over the past two decades. Risk factor-based screening misses a significant proportion of infections. A change to universal maternal screening for hepatitis C would be cost-effective in our population. TWEETABLE ABSTRACT: Universal maternal screening for hepatitis C is cost-effective in this urban Irish population.

Molecular cytogenetic analysis of recurrent unbalanced t(11;17) in neuroblastoma.

Loss of 11q material occurs in approximately 30% of advanced stage neuroblastoma and defines a distinct genetic subtype of this disease. These tumors almost always possess unbalanced gain of the 17q, along with many additional recurrent chromosomal imbalances. Loss of 11q and gain of 17q is often the consequence of an unbalanced translocation between the long arms of both chromosomes, but because of the involvement of other chromosomal mechanisms, the actual frequency of t(11;17) is unknown. In addition, chromosomal breakpoint positions for the t(11;17) are variable in different tumors, with breakpoints on neither the 11q nor 17q being well defined. We have used interphase fluorescence in situ hybridization analysis to detect a der(11)t(11;17) in a series of neuroblastomas with 11q loss/17q gain using a statistical approach which could be applicable to the detection of translocations in other solid tumors. The frequency of der(11)t(11;17) was approximately 90% in our neuroblastoma series. A balanced t(11;17) was also detected in a MYCN amplified tumor, which is a distinctly different genetic subtype from the 11q- tumors. Breakpoint positions on 11q were determined to be variable, whereas all breakpoints on 17q appeared to cluster proximal to position 43.1 Mb on the DNA sequence map. The majority of tumors had large numbers of nuclei with 2 or more copies of der(11)t(11;17), which led to unbalanced gain of 11p, and further increases in 17q imbalance. The prevalence of t(11;17) in neuroblastoma warrants additional studies to further define the range in variation in breakpoint positions on both chromosomes and to elucidate the molecular mechanisms that lead to this important and interesting recurrent genetic abnormality.

Evolution of unbalanced gain of distal chromosome 2p in neuroblastoma.

Neuroblastoma, one of the most common tumors of childhood, presents at diagnosis with a vast number of recurrent chromosomal imbalances that include hyperdiploidy for whole chromosomes, partial loss of 1p, 3p, 4p, 11q, 14q, partial gain of 1q, 7q, 17q and amplification of MYCN. These abnormalities are nonrandomly distributed in neuroblastoma as loss of 3p and 11q rarely occur in MYCN amplified neuroblastomas. Here, we report on a patient who had a non-MYCN amplified 3p-/11q- neuroblastoma at diagnosis who subsequently developed a high level of MYCN amplification in bone marrow metastases 41 months after induction of complete remission. The tumor at diagnosis had low level unbalanced gain of distal 2p. In order to assess the frequency of low level gain of distal 2p in neuroblastoma, we examined the comparative genomic hybridization results from 60 neuroblastomas. Among non-MYCN amplified neuroblastomas, 8/45 (18%) had low level gain of distal 2p. Low level gain for a segment of 2p (i.e. a region larger than the 2p23-->p24 undergoing amplification) was also detected in five of the 15 tumors that had high level MYCN amplification. The possibility that low level gain of distal 2p is a risk factor for high level MYCN amplification is discussed.

Psychometric evaluation of trauma and posttraumatic stress disorder assessments in persons with severe mental illness.

Interrater reliability, internal consistency, test-retest reliability, and convergent validity were examined for the Trauma History Questionnaire (THQ), the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS), and the PTSD Checklist (PCL) in 30 clients with severe mental illnesses. Interrater reliability for the THQ and CAPS was high, as was internal consistency of CAPS and PCL subscales. The test-retest reliability of the THQ was moderate to high for different traumas. PTSD diagnoses on the CAPS and PCL showed moderate test-retest reliability. Lower levels of test-retest reliability for PTSD diagnoses were related to psychosis diagnoses and symptoms. However, when more stringent criteria for PTSD were used on the CAPS, it had excellent test-retest reliability across all clients. CAPS and PCL diagnoses of PTSD showed moderate convergent validity. The results support the reliability of trauma and PTSD assessments in clients with severe mental illness.

Purification of human glutamate dehydrogenase (GDH) and an adsorptive voltammetric investigation of the interaction of GDH with rabbit anti-human GDH antibody.

A procedure for the isolation of glutamate dehydrogenase (GDH) from human liver, which involves the use of ion-exchange chromatography on diethylaminoethyl cellulose and affinity chromatography on guanosine triphosphate conjugated to Sepharose 4B, is described. The adsorptive voltammetric behaviour of human GDH, bovine GDH and rabbit anti-human GDH antibody was optimised with respect to accumulation potential, accumulation time and scan rate. The lower limits of detection were 0.2 and 1.2 mg l-1 for human and bovine GDH, respectively, and the lower limit of detection for rabbit anti-GDH antibody was 0.04 mg l-1. The interaction of human GDH with rabbit anti-human GDH antibody was also examined using this method.

Use of high-performance liquid chromatography for the purification of antibodies and antibody conjugates and the study of antibody-antigen interactions.

The purification and characterization of polyclonal and monoclonal antibodies and antibody-enzyme conjugates by high-performance liquid chromatography (HPLC) using a Protein Pak 300 SW column and a Protein Pak DEAE anion-exchange column is described. The following polyclonal antibodies were examined: (i) donkey anti-mouse immunoglobulin G (IgG), (ii) mouse IgG, (iii) sheep anti-human IgG and (IV) goat anti-human factor VIII. HPLC was used to analyse the purity of horseradish peroxidase conjugates of rabbit anti-mouse IgG and donkey anti-mouse IgG. In the case of donkey anti-mouse IgG, each stage of the production of the purified antibody and antibody-enzyme conjugate was monitored by HPLC. HPLC was used to examine monoclonal mouse anti-human T cell and mouse anti-human apoliproprotein B antibodies. The presence of antibody in ascites fluid from mice bearing Landschütz ascites tumour cells was also detected. The antigen-antibody reaction between human serum albumin and anti-human serum albumin was demonstrated using HPLC and this procedure should offer a novel method for studying antigen-antibody interaction.