Patient, virus, and treatment-related risk factors in pediatric adenovirus infection after stem cell transplantation: results of a routine monitoring program.

Human adenovirus (HAdV) infection after hematopoietic stem cell transplantation (HSCT) is associated with significant morbidity and mortality in children. The optimal surveillance and treatment strategies are under discussion. Here, we present data from 238 consecutive pediatric allogeneic HSCT recipients who underwent transplantation in a single center who were included in a prospective, weekly HAdV DNAemia monitoring program by quantitative PCR. HAdV loads >1000 copies/mL were detected in 15.5% of all patients. Despite a low mortality directly attributed to HAdV infection (2 patients, 0.84%), blood HAdV loads >10,000 copies/mL (6.7% of all patients) were significant and independent risk factors for poor survival. We searched for patient, virus, and treatment-related risk factors of HAdV DNAemia and disease. Detection of HAdV in blood before day 50 post transplantation was a major independent risk factor for the development of blood HAdV loads >10,000 copies/mL. HAdV typing revealed A31, C1, and C2 as the predominant pathogens among several other HAdV strains with type C species detected in most patients with severe HAdV disease. Stool HAdV loads were prospectively monitored in 111 patients and correlated with but did not significantly precede detection in blood. Treatment with cidofovir led to stable or reduced viral load in 70% of patients with blood HAdV loads >1000 copies/mL. Thus, early occurrence of HAdV-DNA in blood of pediatric HSCT recipients predisposes for development of high viral loads. Control of HAdV infections was attempted by preemptive cidofovir treatment of patients with high blood HAdV loads or with symptomatic organ infections and correlated with low HAdV-attributed mortality.

Draft guideline for the development of evidence based medicine-related apps.

Evidence based recommendations can significantly aid decision processes in medicine and mobile apps are starting to enter this domain. Considering the rapid access to and quick processing of information made possible by such apps, it is especially important to ensure the quality and structure of the provided data and to also keep the limitations of the information sources in mind. A draft guideline meant for implementing appropriate standards for such apps is outlined in this contribution.

Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial.

UNLABELLED: Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 µg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group. TRIAL REGISTRATION: ClinicalTrials.gov NCT00803309.

Gender differences in hepatitis C antibody prevalence and risk behaviours amongst people who inject drugs in Australia 1998-2008.

BACKGROUND: Global prevalence of hepatitis C virus (HCV) is estimated to be around 3% with approximately 170 million people affected. In Australia, and in many other resource rich countries, injecting drug use is the single most important risk factor for acquiring HCV, with around a third of diagnoses occurring in women. This study aims to assess gender differences in hepatitis C antibody prevalence and associated risk behaviours amongst a large sample of PWID in Australia. METHODS: During a one to two week period in October, PWID attending selected NSP sites are invited to participate in the Australian NSP Survey. Between 1998 and 2008, approximately 16,000 individuals completed a self-administered questionnaire and provided a capillary blood sample for HIV and HCV antibody testing. We stratified our sample by time since onset of injecting and analysed the demographic characteristics, injecting behaviours and antibody test results to determine gender differences. RESULTS: Women were found to be at increased risk of exposure to hepatitis C in all duration of injection categories except those injecting for 17 or more years. In the early years of injecting, women also reported higher rates of receptive sharing of needles and syringe and ancillary equipment when compared to men. Last injecting heroin, methadone or buprenorphine was significantly associated with HCV antibody prevalence amongst both males and females injecting for less than 5 years. CONCLUSION: Findings indicate that women are at greater risk than men of HCV infection during the early years of injection through higher rates of receptive sharing of needles and syringes and/or ancillary equipment. Our results suggest that women who are new to injecting, and Indigenous women in particular, should be identified as priority populations when developing and implementing harm reduction strategies that target people who inject illicit drugs.

Characterizing trends in HIV infection among men who have sex with men in Australia by birth cohorts: results from a modified back-projection method.

BACKGROUND: We set out to estimate historical trends in HIV incidence in Australian men who have sex with men with respect to age at infection and birth cohort. METHODS: A modified back-projection technique is applied to data from the HIV/AIDS Surveillance System in Australia, including "newly diagnosed HIV infections", "newly acquired HIV infections" and "AIDS diagnoses", to estimate trends in HIV incidence over both calendar time and age at infection. RESULTS: Our results demonstrate that since 2000, there has been an increase in new HIV infections in Australian men who have sex with men across all age groups. The estimated mean age at infection increased from ~35 years in 2000 to ~37 years in 2007. When the epidemic peaked in the mid 1980s, the majority of the infections (56%) occurred among men aged 30 years and younger; 30% occurred in ages 31 to 40 years; and only ~14% of them were attributed to the group who were older than 40 years of age. In 2007, the proportion of infections occurring in persons 40 years or older doubled to 31% compared to the mid 1980s, while the proportion of infections attributed to the group younger than 30 years of age decreased to 36%. CONCLUSION: The distribution of HIV incidence for birth cohorts by infection year suggests that the HIV epidemic continues to affect older homosexual men as much as, if not more than, younger men. The results are useful for evaluating the impact of the epidemic across successive birth cohorts and study trends among the age groups most at risk.