Coexistence of circulating HBsAg and anti-HBs antibodies in chronic hepatitis B carriers is not a simple analytical artifact and does not influence HBsAg quantification

BackgroundPresence at the same time of HBsAg and anti-HBs antibodies (HBsAg/Ab) is an entity sometimes encountered in chronic hepatitis B (CHB) carriers.ObjectivesThis study was designed to characterize such serological profiles and to assess the reliability of serological marker quantification by three commercially available assays in this setting.Study designAmong 2578 CHB identified patients, 129 (5%) had an HBsAg/Ab profile as determined by Abbott Architect. After exclusion of co-infections (HIV, HCV, HDV), HBV reactivation or HBIg treatment, 101 samples from 62 patients were tested for HBsAg and anti-HBs quantification using Architect, DiaSorin Liaison-XL and Roche Modular-Cobas. Influence of genotype and HBsAg variants was studied in 31 samples with HBV replication.ResultsHBsAg detection was confirmed with the 3 techniques for 98% (n = 99) of the samples while the HBsAg/Ab profile was concordant between all techniques for 65% of them. The overall correlation between the 3 HBsAg quantification techniques was good (R²: 0.94–0.97). The median HBsAg concentration was comparable for the 99 samples whatever the used technique but a bias of −0.11 and 0.02 log IU/mL were noticed for DiaSorin and Roche compared to Abbott, respectively. Anti-HBs quantifications were poorly correlated between techniques with major discrepancies observed. Genotype and substitutions within the “a” determinant showed an impact on HBsAg quantification.ConclusionsThe double HBsAg/Ab profile is not an analytical artifact and is confirmed on all commercially available techniques. While such profile does not influence HBsAg quantification, differences of HBsAg quantification were noticed according to HBV genotype or HBsAg variant.     

Clinical performance of the novel DiaSorin LIAISON® XL murex: HBsAg Quant,HCV-Ab,HIV-Ab/Ag assays

BackgroundThe fully automated and closed LIAISON^®XL platform was developed for reliable detection of infection markers like hepatitis B virus (HBV) surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Ab) or human immunodeficiency virus (HIV)-Ag/Ab. To date, less is known about the diagnostic performance of this system in direct comparison to the common Abbott ARCHITECT^® platform.ObjectivesWe compared the diagnostic performance and usability of the DiaSorin LIAISON^®XL with the commonly used Abbott ARCHITECT^® system.Study designThe qualitative performance of the above mentioned assays was compared in about 500 sera. Quantitative tests were performed for HBsAg-positive samples from patients under therapy (n = 289) and in vitro expressed mutants (n = 37). For HCV-Ab, a total number of 155 selected samples from patients chronically infected with different HCV genotypes were tested.ResultsThe concordance between both systems was 99.4% for HBsAg, 98.81% for HCV-Ab, and 99.6% for HIV-Ab/Ag. The quantitative LIAISON^®XL murex HBsAg assay detected all mutants in comparable amounts to the HBsAg wild type and yielded highly reliable HBsAg kinetics in patients treated with antiviral drugs. Dilution experiments using the 2nd International Standard for HBsAg (WHO) showed a high accuracy of this test. HCV-Ab from patients infected with genotypes 1–3 were equally detected in both systems. Interestingly, S/CO levels of HCV-Ab from patients infected with genotype 3 seem to be relatively low using both systems.ConclusionsThe LIAISON^®XL platform proved to be an excellent system for diagnostics of HBV, HCV, and HIV with equal performance compared to the ARCHITECT^® system.     

Performance of HBsAg quantification assays for detection of Hepatitis B virus genotypes and diagnostic escape-variants in clinical samples

BackgroundThe impact of hepatitis B virus (HBV) genomic variability on the measurement of HBsAg level has been poorly evaluated.ObjectiveThis study was designed to compare the performance of all the available assays measuring HBsAg level in this setting.Study designA large selection of wild type HBV genotypes (n = 184) and HBsAg strains harboring mutations in the S gene (n = 81) from clinical samples was studied with three HBsAg quantification assays: Architect HBsAg (Abbott), LiaisonXL Murex HBsAg Quant (DiaSorin) and the Elecsys HBsAgII (Roche).ResultsThe overall percentage of positive results was 99.2% for Abbott, 98.9% for DiaSorin and 98.1% for Roche. Abbott and Roche assays provided an excellent concordance in HBsAg quantification (global mean bias of −0.006 logIU/mL). By contrast, DiaSorin underestimated HBsAg level with values 0.112 logIU/ml and 0.103 logIU/ml lower than Abbott and Roche, respectively. By contrast, DiaSorin slightly over quantified gtC (2.5% over the expected value) while Abbott provided values 6.2% lower than expected and 16.2% lower than what observed for the other genotypes. HBsAg quantitative assays were influenced by HBs protein substitutions irrespective to the genotype but no specific protein pattern that would particularly impair the quantification by one technique has been identified. However, Roche seemed to be particularly impacted by substitutions at 145 residue: 75% of under quantified samples carried a substituted 145 residue.ConclusionThis head-to-head comparison indicates a good correlation between all current systems used to quantify HBsAg but clearly shows an influence of both the genotype and the presence of “a” determinant variants in the absolute quantification of HBsAg. While these discrepancies may not translate into major clinical consequence, they may explain an absence of detection of weak concentration of HBsAg on some systems.     

Diagnostic performance of serological assays for anti-HBs testing: Results from a quality assessment program

BackgroundPost-vaccination testing after hepatitis B vaccination is indispensable to evaluate long-term immunological protection. Using a threshold level of antibodies against hepatitis B surface antigen (anti-HBs) to define serological protection, implies reproducible and valid measurements of different diagnostic assays.ObjectivesIn this study we assess the performance of currently used anti-HBs assays.Study designIn 2013, 45 laboratories participated in an external quality assessment program using pooled anti-HBs serum samples around the cutoff values 10 IU/l and 100 IU/l. Laboratories used either Axsym (Abbott Laboratories), Architect (Abbott Laboratories), Access (Beckman-Coulter), ADVIA Centaur anti-HBs2 (Siemens Healthcare Diagnostics), Elecsys, Modular or Cobas (Roche Diagnostics) or Vidas Total Quick (Biomerieux) for anti-HBs titre quantification. We analysed covariance using mixed-model repeated measures. To assess sensitivity/specificity and agreement, a true positive or true negative result was defined as an anti-HBs titre respectively above or below the cutoff value by ≥4 of 6 assays.ResultsDifferent anti-HBs assays were associated with statistically significant (P < 0.05) differences in anti-HBs titres in all dilutions. Sensitivity and specificity ranged respectively from 64%-100% and 95%-100%. Agreement between assays around an anti-HBs titre cutoff value of 10 IU/l ranged from 93%-100% and was 44% for a cutoff value of 100 IU/l.ConclusionsAround a cutoff value of 10 IU/l use of the Access assay may result in false-negative results. Concerning the cutoff value of 100 IU/l, a sample being classified below or above this cutoff relied heavily on the specific assay used, with both the Architect and the Access resulting in false-negative results.     

Correlation between the Elecsys HBsAg II assay and the Architect assay for the quantification of hepatitis B surface antigen (HBsAg) in the serum

BackgroundHepatitis B surface antigen (HBsAg) clearance during chronic hepatitis B (CHB) infection is associated with improved long-term clinical outcome, so is considered an important therapeutic goal in CHB. Studies have shown that serum HBsAg quantification during, and at end of, treatment may predict long-term HBsAg loss.ObjectivesPerformance comparison of the qualitative Elecsys HBsAg II assay using a quantitative research protocol and an established quantitative HBsAg assay.Study designA dilution algorithm was developed for the Elecsys HBsAg II assay to allow quantification of HBsAg levels; this was used to measure HBsAg levels in a range of samples including sera from patients infected with different HBV genotypes, HBV mutants, and longitudinal samples from patients undergoing antiviral treatment. Results were compared with those from the quantitative Architect HBsAg assay.ResultsThere was significant overall correlation between Elecsys and Architect assays (correlation coefficient [r] = 0.97; p < 0.001). HBsAg levels measured with both assays correlated well in all phases of infection (r = 0.80–0.96), across all genotypes tested (HBV genotype A, r = 0.89; HBV genotype D, r = 0.97), and in samples with lamivudine-resistant mutations (r = 0.94). Bland–Altman analysis showed only minor discordance between assays in different phases of chronic HBV-infection (3.8–5.1%). This strong correlation was also present for sera with lower HBsAg concentrations. On-treatment HBsAg levels were similar when measured with either assay.ConclusionsUsing a simple dilution algorithm, the quantitative Elecsys HBsAg II assay reliably determined serum HBsAg levels in a wide range of samples, and showed very high correlation with the Architect HBsAg assay.     

CTL escape mutations of core protein are more frequent in strains of HBeAg negative patients with low levels of HBV DNA

BackgroundRecent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV).ObjectivesWe aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs).Study designAmino acids 1–150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants.ResultsAmino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p = 0.014). Asn⁶⁷ mutation was mutually exclusive to the combination Ile⁶⁶ and Ser⁶⁹ (P < 0.001). Substitutions for Ser²¹ and Thr12Ser were associated with lower serum levels of HBV DNA (p < 0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18–27, had serum HBV DNA more than 10⁵ copies/mL (p < 0.001). By multivariate analysis, high level (>10⁵ copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p = 0.015), while it was directly associated with the presence of promoter double T¹⁷⁶²A¹⁷⁶⁴ mutations together with G¹⁷⁵⁷ (OR: 16.87, p = 0.004).ConclusionThe inverse correlation between serum levels of HBV DNA and CTL escape mutations of the core protein in HBeAg seroconverted patients, supports the notion that selection of CTL escape mutations consolidates the persistence of HBV infection despite reducing viral fitness.     

Performance and clinical utility of a novel fully automated quantitative HCV-core antigen assay

BackgroundRecently, a novel quantitative HCVcoreAg immunoassay developed for commercialisation by Abbott has become available in Europe and Asia.ObjectivesWe evaluated the correlation of HCV-RNA and HCVcoreAg and investigated the stability of HCVcoreAg and HCV-RNA.Study designHCVcoreAg was quantified by a novel fully automated immunoassay (Architect HCVAg, Abbott, Germany). HCV-RNA quantification was performed either using the Cobas-TaqMan assay or Amplicor-HCV-Monitor (Roche-Diagnostics, Germany). Correlation of HCVcoreAg with HCV-RNA was studied cross-sectionally and longitudinally in untreated patients followed for up to 8 years. Stability of HCVcoreAg and HCV-RNA was evaluated in plasma and whole blood stored for up to 96 h at different conditions.ResultsHCVcoreAg showed good correlation with HCV-RNA in all 118 cross-sectional tested samples irrespective of the HCV genotype (r = 0.75). In the majority but not all of the 10 longitudinally studied patients HCVcoreAg also demonstrated a good correlation with HCV-RNA. HCVcoreAg was stable in plasma at 4, 20, and 37 °C for up to 96 h, whereas HCV-RNA significantly declined at 37 °C. In whole blood, HCVcoreAg and HCV-RNA levels declined at all conditions with exception of HCVcoreAg at 37 °C. HCVcoreAg was stable after 1–5 freezing/thawing cycles and not light-sensitive.ConclusionsHCVcoreAg represents a stable and reliable marker of viral replication showing a good correlation with HCV-RNA irrespective of the HCV genotype. HCVcoreAg determination can be used to confirm viral replication and monitor viral load or acquisition of HCV over time.     

Clinical implications of hepatitis B surface antigen quantitation in the natural history of chronic hepatitis B virus infection

BackgroundHBsAg quantitation may be useful for managing patients with hepatitis B virus (HBV) infection.ObjectivesWe explored the clinical implications of HBsAg quantitation for patients with HBsAg levels >250 IU/ml (Abbott Diagnostics).Study designTwo hundred and thirty-three HBV-infected patients comprising 29 immune tolerance cases, 49 treatment-naïve HBeAg-positive chronic hepatitis B (CHB) cases, 91 inactive HBV carrier cases, and 64 treatment-naïve HBeAg-negative CHB cases were analyzed. HBsAg was quantified by the Architect HBsAg assay (Abbott Diagnostics) after a 1:500 automated dilution.Results and conclusionsHBsAg (log 10 IU/ml) was established for immune tolerance (4.50 ± 0.43), HBeAg-positive CHB (4.17 ± 0.66), inactive HBV carrier (3.32 ± 0.44), and HBeAg-negative CHB (3.23 ± 0.40); (p = 4.92 × 10⁻³⁵). No significant difference was observed between inactive HBV carrier and HBeAg-negative CHB (p = 0.247). The proportions of HBsAg <2000 IU/ml for inactive HBV carrier and HBeAg-negative CHB were 51.6% and 59.3%, respectively (p = 0.341). Positive correlations between HBsAg and HBV DNA were observed for immune tolerance (p = 1.23 × 10⁻⁴) and HBeAg-positive CHB (p = 0.003), but not for HBeAg-negative CHB (p = 0.432). A negative correlation between HBsAg and age was observed for immune tolerance (p = 0.030), HBeAg-positive CHB (p = 0.016), and inactive HBV carrier (p = 0.001), but not in HBeAg-negative CHB (p = 0.249). No significant differences between HBsAg and ALT for HBeAg-positive (p = 0.338) or HBeAg-negative CHB (p = 0.564) were observed. For patients with HBsAg quantitation >250 IU/ml, HBsAg may reflect HBV DNA replication for HBeAg-positive cases. HBsAg is not a suitable marker for evaluating hepatitis activity and distinguishing between cases of HBeAg-negative CHB and inactive HBV carrier state.     

Outcomes of passive-active immunoprophylaxis given to infants of mothers infected with hepatitis B virus in Babol,Iran

BackgroundInfants born to chronic hepatitis B virus (HBV) infected mothers may be infected in spite of receiving passive-active immunoprophylaxis.ObjectivesThe purpose of this study was to assess the outcome of infants born to women actively infected by HBV.Study designFrom April 2004 to September 2009, infants born to women actively infected by HBV received hepatitis B immune globulin (HBIG) and the first dose of hepatitis B vaccine at birth. The second and third doses of HBV vaccine were administered at 1 and 6 months of age. Post-vaccination tests to detect HBsAg and anti-HBs were assessed between 12 and 15 months of age. Those who had anti-HBs titers < 10 mIU/ml received the second series of HBV vaccine.ResultsThirty-four and 201 infants were born to HBeAg-seropositive and anti-HBe-seropositive mothers, respectively. HBsAg was detected in 6 (17.6%) infants born to HBeAg-seropositive mothers and in 3 (1.5%) to anti-HBe-seropositive mothers (p = 0.0001). Anti-HBs ≥ 10 mIU/ml were achieved in 26 (76.5%) and 178 (88.6%) infants of HBeAg-seropositive and anti-HBe-seropositive mothers, respectively (p > 0.05). Twenty-two (9.4%) infants were non-responders and 11(50%) of them responded to the second series of HBV vaccine.ConclusionsThe results show that infants of HBeAg-seropositive mothers have higher risk of developing of HBV infection. Some HBsAg-seronegative infants may not respond to passive-active immunoprophylaxis and may remain at risk of HBV infection.     

Development of anti-hepatitis B surface (HBs) antibodies after HBs antigen loss in HIV-hepatitis B virus co-infected patients

BackgroundHepatitis B surface antigen (HBsAg)-seroconversion, or loss of HBsAg and acquisition of anti-hepatitis B surface (HBs) antibodies, defines functional cure of chronic hepatitis B virus (HBV) infection. After HBsAg-loss, little is known regarding the development of anti-HBs antibodies and even less so in individuals co-infected with HIV.ObjectivesTo determine anti-HBs antibody kinetics after HBsAg-loss and explore determinants of HBsAg-seroconversion in HIV-HBV co-infected patients.Study designPatients enrolled in the French HIV-HBV cohort were included if they had >1 study visit after HBsAg-loss. Individual patient kinetics of anti-HBs antibody levels were modeled over time using mixed-effect non-linear regression, whereby maximum specific growth rate and maximal level of antibody production were estimated from a Gompertz growth equation.ResultsFourteen (4.6%) of 308 co-infected patients followed in the cohort exhibited HBsAg-loss, all of whom were undergoing antiretroviral therapy. Nine (64.3%) of these patients achieved HBsAg-seroconversion during a median 3.0 years (IQR = 1.1–5.1) after HBsAg-loss. Across individuals with HBsAg-seroconversion, the fastest rates of antibody growth ranged between 0.57–1.93 year⁻¹ (population maximum growth rate = 1.02) and antibody production plateaued between 2.09–3.66 log₁₀ mIU/mL at the end of follow-up (population maximal antibody levels = 2.66). Patients with HBsAg-seroconversion had substantial decreases in HBV DNA viral loads (P = 0.03) and proportion with elevated ALT levels (P = 0.02) and HBeAg-positive serology (P = 0.08). No such differences were observed in those without HBsAg-seroconversion.ConclusionsMost co-infected patients with HBsAg-seroconversion produced and maintained stable antibody levels, yet kinetics of anti-HBs production were much slower compared to those observed post-vaccination or after clearance of acute HBV-infection.     

Evaluation of the performance of a new automated HIV combination assay

BackgroundMore and more countries test for HIV infection using combination assays that simultaneously detect p24 antigen and HIV antibodies.ObjectiveTo assess the performance of a new HIV combo assay: LIAISON^® XL murex HIV Ab/Ag HT.Study designThe assays were examined with a total of 3090 samples that included 769 selected HIV antibody-negative samples, 1849 unselected HIV samples, 15 HIV-1 p24 Ag reference samples, 90 primary HIV-1 infection (PHI) samples, 167 HIV-1 antibody-positive samples (well characterized of groups M and O), 95 HIV-1 antibody-positive samples and 105 HIV-2 antibody-positive samples.ResultsThe specificity of the LIAISON^® XL murex HIV Ab/Ag HT was 99.7%. The analytical sensitivity of Ag p24 of the LIAISON^® XL murex HIV Ab/Ag HT was 0.58 IU/mL and 9.93 pg/mL when using WHO and French national standards, respectively. All screened HIV subtypes was identified by this assay. Also, 90 PHI specimens were detected by this screening assay.ConclusionThe sensitivity and specificity of the LIAISON^® XL murex HIV Ab/Ag HT assay are high. Hence the assay offers automated high-throughput screening with ability to detect primary infection.     

Detection of human rhinovirus C in fecal samples of children with gastroenteritis

BackgroundDespite recent discovery of the novel human rhinovirus species, HRV-C, little is known about the association of HRV-C in diseases other than respiratory tract infections.ObjectivesTo investigate the presence of HRV-C in fecal samples of children with gastroenteritis.Study design734 fecal samples from hospitalized children with gastroenteritis were subject to picornavirus detection by RT-PCR of the conserved 5′-NCR. Positive samples were subject to VP4 and 3D^pol gene analysis for species determination. The clinical and molecular epidemiology of HRV-C and other picornaviruses was analyzed.ResultsPicornaviruses were detected in 113 (15.4%) of 734 fecal samples from children with gastroenteritis by RT-PCR of 5′-NCR, with 58 containing potential HRVs and 55 containing other enteroviruses. PCR of the VP4 and 3D^pol regions was positive in 21 and 19 samples respectively (both regions positive in 8 samples). Sequencing analysis showed the presence of HRV-C in four samples, and diverse picornaviruses including HRV-A (n = 2), HEV-A (n = 2), HEV-B (n = 2), HEV-C (n = 21) and HPeV (n = 2) in other samples, with co-detection of HRV-C and HPeV in one sample. Of the four children with HRV-C detected in fecal samples, three presented with diarrhea in the absence of respiratory symptoms, while one also had acute bronchiolitis. The four HRV-C strains from fecal samples belonged to the existing clade of diverse HRV-C genotypes, indistinguishable from previous respiratory strains.ConclusionsHRV-C can be detected in fecal samples of children with gastroenteritis, in the absence of respiratory symptoms. This study also represented the first to detect HPeV in our population.     

Pretreatment cerebral metabolic activity correlates with antidepressant efficacy of vagus nerve stimulation in treatment-resistant major depression: A potential marker for response?

BackgroundPretreatment brain activity in major depressive disorder correlates with response to antidepressant therapies, including pharmacotherapies and transcranial magnetic stimulation. The purpose of this trial was to examine whether pretreatment regional metabolic activity in selected regions of interest (ROIs) predicts antidepressant response following 12 months of vagus nerve stimulation (VNS) in 15 patients with treatment-resistant major depression (TRMD).MethodsFluorodeoxyglucose positron emission tomography (FDG PET) was used to assess regional mean relative cerebral metabolic rate for glucose (CMRGlu) in four ROIs (anterior insular, orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices) at baseline (prior to VNS activation). Depression severity was assessed at baseline and after 12 months of VNS using the Hamilton Depression Rating Scale (HDRS), with response defined as ≥ 50% reduction in HDRS from baseline.ResultsBaseline CMRGlu in the anterior insular cortex differentiated VNS responders (n = 11) from nonresponders (n = 4) and correlated with HDRS change (r = .64, p = .01). In a regression analysis, lower anterior insular cortex CMRGlu (p = .004) and higher orbitofrontal cortex CMRGlu (p = .047) together predicted HDRS change (R² = .58, p = .005). In a whole brain, voxel-wise analysis, baseline CMRGlu in the right anterior insular cortex correlated with HDRS change (r = .78, p = .001).LimitationsSample size was small, limiting statistical power; patients remained on their psychiatric medications; study was open-label and uncontrolled.ConclusionsThis preliminary study suggests that pretreatment regional CMRGlu may be useful in predicting response to VNS in TRMD patients.     

The effect of relaxin on the female anterior cruciate ligament: Analysis of mechanical properties in an animal model

BackgroundThe peptide hormone relaxin, found in pregnant and non-pregnant females, has been shown to have collagenolytic effects on ligamentous tissue. Relaxin receptors have recently been identified on the human female anterior cruciate ligament (ACL). Relaxin may affect the load bearing properties of the female ACL and contribute to non-contact ACL injuries.HypothesisThe administration of recombinant relaxin ± estrogen will lead to a significant decrease in ACL integrity in the guinea pig model.Study designControlled laboratory study.MethodsAdult female guinea pigs were divided into three experimental groups. Group 1 (n = 4) was administered only 20 µg/h of recombinant porcine relaxin for 3 weeks. Group 2 (n = 4) was administered 20 µg/h of recombinant porcine relaxin and 5 µg/h of estradiol for 3 weeks. Group 3 (n = 4) served as both a normal control before surgical transection of the ACL and a positive ACL tear control after transection. All hormones were administered using separate implanted osmotic pumps. ACL laxity was tested by implanting radio-opaque markers in the femur and tibia of each leg. After applying a standard anterior force (22 N), the distance between markers was measured radiographically at day 0 and day 21. The animals were then sacrificed and the ACL's were analyzed for load-to-failure using a material testing machine.ResultsLoad-to-failure testing indicated that animals treated with relaxin only had significantly weaker ACL's (µ = 40.4 N, p = 0.001) compared to controls (µ = 64.1 N). The relaxin + estrogen group (µ = 32.7 N) was also significantly weaker than controls (p = 0.007). There were no statistical differences between relaxin and relaxin + estrogen groups. Both relaxin only and relaxin + estrogen groups showed an increase in anterior translation of the tibia after 3 weeks of infusion, but it did not achieve statistical significance.ConclusionsRelaxin significantly alters the mechanical properties of the ACL in an animal model.Clinical relevanceThe effects of relaxin, possibly in conjunction with estrogen, may contribute to a comprehensive etiology for human female non-contact ACL injuries.     

Prevalence and correlates of physical and sexual abuse in children and adolescents with bipolar disorder

ObjectiveAdult bipolar disorder (BP) has been associated with lifetime history of physical and sexual abuse. However, there are no reports of the prevalence of abuse in BP youth. The objective of this study was to examine the prevalence and correlates of physical and/or sexual abuse among youth with BP spectrum disorders.MethodsFour hundred forty-six youths, ages 7 to 17 years (12.7 ± 3.2), meeting DSM-IV criteria for BP-I (n = 260), BP-II (n = 32) or operationalized definition of BP-NOS (n = 154) were assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children—Present and Lifetime version (K-SADS-PL). Abuse was ascertained using the K-SADS.ResultsTwenty percent of the sample experienced physical and/or sexual abuse. The most robust correlates of any abuse history were living with a non-intact family (OR = 2.6), lifetime history of posttraumatic stress disorder (PTSD) (OR = 8.8), psychosis (OR = 2.1), conduct disorder (CD) (OR = 2.3), and first-degree family history of mood disorder (OR = 2.2). After adjusting for confounding demographic factors, physical abuse was associated with longer duration of BP illness, non-intact family, PTSD, psychosis, and first-degree family history of mood disorder. Sexual abuse was associated with PTSD. Subjects with both types of abuse were older, with longer illness duration, non-intact family, and greater prevalence of PTSD and CD as compared with the non-abused group.LimitationsRetrospective data. Also, since this is a cross-sectional study, no inferences regarding causality can be made.ConclusionSexual and/or physical abuse is common in youth with BP particularly in subjects with comorbid PTSD, psychosis, or CD. Prompt identification and treatment of these youth is warranted.     

An empirical study of characteristics and types of homicide-suicides in Hong Kong, 1989-2005

BackgroundClinical classification of types of homicide–suicide (HS) was proposed, but no information on empirical-based classification and prevalence of different types of HS was available. This paper aimed to empirically classify HS events into different clusters and to discuss specific evidence-based prevention initiatives.MethodData of HS offenders from Coroner's Court were analyzed through a two-step cluster analysis. Number of clusters and appropriate allocations of cases were obtained. External background variables were tested through post hoc tests to explore the differences among clusters.ResultsTwo hundred and thirty-one people died in 98 episodes in the study period (1989–2005). The majority of HS offenders were male (n = 68, 68.7%) and aged 30–49 (n = 62, 62.6%). Domestic killing was the major type of HS in which over 60% of the homicide motivation was related to spousal conflicts or altruistic reasons. Spouses (n = 46, 46.5%) and children (n = 47, 47.5%) were predominantly the victims. The common killing methods included chopping with weapons (n = 33, 33.3%) and charcoal burning (n = 22, 22.2%). Six clusters of HS were derived from the cluster analysis and were further reduced to four major classes. Four major classes were dispute, conflicts in a relationship, altruistic, and mental illness. These classes could be differentiated by methods of homicide and suicide, gender of perpetrator, relationship with victim, and indebtedness.ConclusionsFinancial problem, dispute and domestic violence are significant precipitants of HS in Hong Kong. Those people associated with the precipitating factors should be the targets for intervention and prevention.     

A new highly automated extraction system for quantitative real-time PCRs from whole blood samples: routine monitoring of opportunistic infections in immunosuppressed patients

BackgroundRapid, high throughput extraction systems are needed to monitor viral infections in immunosuppressed patients.ObjectivesEvaluate the performance of the MagNA Pure 96? extraction system, and compare it to the COBAS Ampliprep? for quantitative real-time PCR from whole blood samples.Study designCompare the MagNA Pure LC?, COBAS Ampliprep? and MagNA Pure 96? using ten-fold dilutions of blood samples containing cytomegalovirus. Evaluate analytical performances of the MagNA Pure 96? from test samples containing cytomegalovirus. Evaluate clinical performances from 209 blood samples collected prospectively, extracted with the COBAS Ampliprep? and the MagNA Pure 96? systems and tested for cytomegalovirus, Epstein–Barr, BK and JC viruses.ResultsAll three extraction systems gave similar results with dilutions of a cytomegalovirus-positive sample. Analytical tests showed that the limit of detection was 500 copies/ml, specificity was 100%, with no cross-contamination. Quantification was linear from 3.0 to 6.0 log₁₀ copies/ml. Intra-assay variation was 8.3–0.9% and inter-assay variation 8.8–5.2%. Clinical specimens extracted with the MagNA Pure 96? and COBAS Ampliprep? instruments agreed well for cytomegalovirus (r = 0.54; p = 0.07), Epstein–Barr virus (0.69; p = 0.0005) and BK virus (0.85; p = 0.01). All 55 samples were negative for JC virus. Mean loads were similar for cytomegalovirus (0.17 log₁₀ copies/ml) and BK virus (?0.24 log₁₀ copies/ml) while that of Epstein–Barr virus was slightly lower (1.02 log₁₀ copies/ml).ConclusionsThe MagNA Pure 96? instrument is an easy-to-use, reliable high throughput platform for extracting nucleic acid from clinical whole blood specimens.     

Low pretreatment serum HBsAg level and viral mutations as predictors of response to PEG-interferon alpha-2b therapy in chronic hepatitis B

BackgroundViral genomic mutations have become increasingly recognized as being associated with the outcome of chronic HBV infection. However, the role of viral mutations as a predictor of response to pegylated-interferon (PEG-IFN) therapy has so far remained unclear.Study designViral mutations in the enhancer II/basal core promoter (BCP)/precore and the pre-S regions were characterized by direct sequencing in pretreatment serum samples of 50 patients with chronic hepatitis B (33 HBeAg-positive and 17 HBeAg-negative), who were treated for 48 weeks with PEG-IFN alpha-2b.ResultsSustained virological response at 48 weeks post treatment, defined as HBeAg seroconversion and HBV DNA < 2000 IU/mL for HBeAg-positive patients, and HBV DNA < 200 IU/mL for HBeAg-negative patients, was achieved in 12 (36.4%) and 6 (35.3%) of HBeAg-positive and HBeAg-negative patients, respectively. Response to PEG-IFN therapy correlated to low pretreatment HBsAg level but did not correlate with HBV genotype, pretreatment alanine transaminase and HBV DNA levels. In HBeAg-positive hepatitis, PEG-IFN response correlated with the appearance of double BCP mutations (A1762T/G1764A) at baseline (P = 0.041). In the HBeAg-negative group, response to PEG-IFN therapy was associated with the presence of pre-S mutation/deletions (P = 0.028). Multivariate analysis identified low pretreatment HBsAg level as an independent factor associated with SVR in both groups.ConclusionsPretreatment quantitative HBsAg determination is useful for predicting response to PEG-IFN therapy. The presence of double BCP and pre-S mutation/deletions at entry may be associated with a high rate of antiviral response in HBeAg-positive and HBeAg-negative hepatitis, respectively.     

Aberrant expression of cell cycle regulatory genes predicts overall and disease free survival in malignant pleural mesothelioma patients

BackgroundMalignant pleural mesothelioma (MPM) is a highly aggressive disease with a generally poor prognosis. Since escape from cell cycle checkpoint control is common in several solid tumors, the present study was performed to evaluate the role of some cell cycle regulatory genes in the development and progression of MPM.Patients and methodsAberrant expression of p14^ARF, p16^INK4A, p21^waf, p27^KIP, p53, mdm2 and Rb was assessed in 55 MPM cases from Egypt using immunohistochemistry and PCR techniques. Results were correlated with clinico-pathological prognostic factors, overall and disease free survival (OS&;DFS).ResultsAltered expression of p14^ARF, p16^INK4A, p21^waf, p27^KIP1, Rb, p53 and mdm2 proteins was detected in 50.9%, 54.5%, 53.3%, 61.8%, 53.3%, 58.2%, and 50.8% of cases, respectively. SV40 infection significantly correlated with p14^ARF, 16^INK4A, p27^kip1 and Rb aberrations (p = 0.014, p = 0.02, p = 0.01, p = ? 0.01). Asbestos exposure significantly correlated with p53, p21^waf and mdm2 aberrations (p = 0.001, p = 0.03, p = 0.02). On multivariate analysis PS ≥ 2, p27^KIP1 and Rb aberrations were independent prognostic factors for OS (p = 0.016, p = 0.011, p = 0.003) whereas on tumor recurrence, p27^KIP1 and Rb aberrations were independent prognostic factors for DFS (p = 0.002, p = 0.03, p = 0.01).ConclusionsMPM is a complex disease characterized by multiple genetic aberrations; some of them involve cell cycle regulatory genes. p14^ARF, p16^INK4A, Rb and p27^KIP1 seem to be involved in SV40-associated MPM whereas mdm2, p53 and p21^WAF are related to asbestos exposure. In addition to recurrence and PS, only p27^KIP1and Rb could be used as molecular prognostic markers in MPM.     

Changes in women's attitudes towards and use of hormone therapy after HERS and WHI

Objectives:To assess changes in women's attitudes towards risk and benefits of, and use of hormone treatment in the menopausal transition (HT) before and after Heart and Estrogen/Progestin Replacement Study (HERS) and the oestrogen and progestin trial of Women's Health Initiative (WHI).Methods:Postal questionnaires to all women 53 and 54 years of age in a Swedish community in 1999 (n = 1.760) and 2003 (n = 1.733). Data on sales of HT were collected from the database of the National Corporation of Swedish Pharmacies.Results:The fraction of women reporting current use of HT fell from 40.5 to 25.3% (p < 0.001, χ²-test) both by fewer women starting and more women discontinuing treatment. This corresponded to a decrease in dispensation of HT in Linköping and nationwide for the same age group. The fraction of women who had tried complementary treatment for climacteric discomfort, increased from 9.6 to 18.1% for natural remedies (p < 0.001, χ²-test).Women perceived HT as more risky and less beneficial in 2003 as compared with 1999 (both p < 0.001, χ²-test). The most frequent source of information about HT during the last year before the 2003 questionnaire were newspaper or magazines (43.8%) and television or radio (31.7%).Conclusions:The decreased use of HT in the community correlated with pronounced changes in the attitudes towards HT. Media were a more frequent source of information than health care personnel. This indicates that media reports about major clinical studies might have influenced the use of HT among women.