156 research outputs found
sj-pdf-1-jva-10.1177_11297298231153716 – Supplemental material for Trimmed central venous catheters do not increase endothelial injury in an ovine model
No full textSupplemental material, sj-pdf-1-jva-10.1177_11297298231153716 for Trimmed central venous catheters do not increase endothelial injury in an ovine model by Hanjay Wang, Kiah M Williams, Stefan Elde, Philip L Bulterys, Akshara D Thakore, Haley J Lucian, Justin M Farry, Danielle M Mullis, Yuanjia Zhu, Michael J Paulsen and Y Joseph Woo in The Journal of Vascular Access</p
Antiviral kinetics of tenofovir alafenamide and tenofovir disoproxil fumarate over 24 weeks in women of childbearing potential with chronic HBV
No full textBACKGROUND/PURPOSE: Use of tenofovir disoproxil fumarate (TDF) improves patient outcomes in preventing mother-to-child transmission (pMTCT) of the hepatitis B virus (HBV) in mothers with chronic HBV and high viral loads. Given the lack of data for tenofovir alafenamide (TAF) in pMTCT, rates of early viral suppression with TAF and TDF were evaluated in women of childbearing potential (WOCBP) participating in 2 randomized, double-blind, Phase 3 studies in chronic HBV. METHODS: In a patient subset meeting WOCBP criteria and with baseline HBV DNA >200,000 IU/mL, rates of viral suppression with TAF or TDF in achieving the target of HBV DNA <200,000 IU/mL at weeks 12 and 24 were assessed. Multivariate logistic regression was used to identify factors predictive of failure to suppress HBV DNA to the target level. RESULTS: In 275 of 1298 (21%) patients meeting WOCBP criteria with high viral load, 93% and 96% had HBV DNA <200,000 IU/mL at weeks 12 and 24, respectively. Results for TAF (n = 194) vs TDF (n = 81) treatment were similar at weeks 12 and 24 (94% vs. 90% and 97% vs. 93%), respectively. High baseline HBV DNA level, genotype D infection, and prior interferon (week 24 only) were predictive of failure to achieve the target level. Both treatments were well tolerated with TAF showing less impact on renal and bone parameters. CONCLUSIONS: In WOCBP with high VL, no differences were found between TAF and TDF in reducing HBV DNA to levels associated with lower transmission risk. These data support ongoing studies of TAF for pMTCT
Duration of ruptured membranes and vertical transmission of HIV-1: a meta-analysis from 15 prospective cohort studies.
No full textOBJECTIVE: To test the a priori hypothesis that longer duration of ruptured membranes is associated with increased risk of vertical transmission of HIV.
DESIGN: The relationship between duration of ruptured membranes and vertical transmission of HIV was evaluated in an individual patient data meta-analysis.
METHODS: Eligible studies were prospective cohort studies including at least 100 mother-child pairs, from regions where HIV-infected women are counselled not to breastfeed. Analyses were restricted to vaginal deliveries and non-elective Cesarean sections; elective Cesarean section deliveries (those performed before onset of labour and before rupture of membranes) were excluded.
RESULTS: The primary analysis included 4721 deliveries with duration of ruptured membranes < or = 24 h. After adjusting for other factors known to be associated with vertical transmission using logistic regression analysis to assess the strength of the relationship, the risk of vertical HIV transmission increased approximately 2% with an increase of 1 h in the duration of ruptured membranes [adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.04; for each 1 h increment]. There were no significant interactions of duration of ruptured membranes with study cohort or with any of the covariates, except maternal AIDS. Among women diagnosed with AIDS, the estimated probability of transmission increased from 8% to 31% with duration of ruptured membranes of 2 h and 24 h respectively (P < 0.01).
CONCLUSIONS: These results support the importance of duration of ruptured membranes as a risk factor for vertical transmission of HIV and suggest that a diagnosis of AIDS in the mother at the time of delivery may potentiate the effect of duration of ruptured membrane
Interventions to prevent vertical transmission of HIV-1: effect on viral detection rate in early infant samples.
No full textAn in situ high-throughput screen identifies inhibitors of intracellular Burkholderia pseudomallei with therapeutic efficacy
No full textBurkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Tier-1 Select
Agents that cause melioidosis and glanders, respectively. These are highly lethal
human infections with limited therapeutic options. Intercellular spread is a
hallmark of Burkholderia pathogenesis, and its prominent ties to virulence make
it an attractive therapeutic target. We developed a high-throughput cell-based
phenotypic assay and screened ∼220,000 small molecules for their ability to
disrupt intercellular spread by Burkholderia thailandensis, a closely related
BSL-2 surrogate. We identified 268 hits, and cross-species validation found 32
hits that also disrupt intercellular spread by Bp and/or Bm Among these were a
fluoroquinolone analog, which we named burkfloxacin (BFX), which potently
inhibits growth of intracellular Burkholderia, and flucytosine (5-FC), an
FDA-approved antifungal drug. We found that 5-FC blocks the intracellular life
cycle at the point of type VI secretion system 5 (T6SS-5)-mediated cell-cell
spread. Bacterial conversion of 5-FC to 5-fluorouracil and subsequently to
fluorouridine monophosphate is required for potent and selective activity against
intracellular Burkholderia In a murine model of fulminant respiratory
melioidosis, treatment with BFX or 5-FC was significantly more effective than
ceftazidime, the current antibiotic of choice, for improving survival and
decreasing bacterial counts in major organs. Our results demonstrate the utility
of cell-based phenotypic screening for Select Agent drug discovery and warrant
the advancement of BFX and 5-FC as candidate therapeutics for melioidosis in
human
Hepatitis C virus infection in children and adolescents
No full textHepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have transformed treatment for HCV infection. Since the 2016 launch of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on the treatment of adults, who bear the greatest burden of morbidity and mortality of HCV-related chronic liver disease. Compared with adults, there has been little attention paid to addressing the response to HCV in children and adolescents, in part because of the scarcity of data to inform specific paediatric management practices and policy. In this Series paper, we summarise knowledge on the epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and we highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden of HCV infection in children aged 1–19 years is 0·15%, corresponding to 3·5 million people (95% CI 3·1–3·9 million). HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir with ledipasvir and sofosbuvir with ribavirin have received regulatory approval and guidelines recommend their use in adolescents aged 12 years and older with HCV infection. In April, 2019, glecaprevir with pibrentasvir also received regulatory approval for adolescents aged 12–17 years. Key actions to address the current policy gaps and achieve treatment scale-up that is comparable to that in adults include: establishment of a campaign on access to testing and treatment that is targeted at children and adolescents; fast-track evaluation of pan-genotypic regimens; and accelerated approval of paediatric formulations. Research gaps that need to be addressed include: age-specific prevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests for staging of liver disease in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agendas
Hepatitis B virus infection in children and adolescents
No full textHepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease and associated morbidity and mortality worldwide. Vertical (mother-to-child) and horizontal early childhood transmission are the main routes of HBV transmission and are responsible for most chronic infections, including among adults who bear the greatest burden of morbidity and mortality. Universal hepatitis B immunisation at birth and in infancy is the key strategy for global elimination of HBV infection, and has been highly effective in reducing new vertical infections. However, global progress in scale-up of HBV testing and treatment has been slow in adults and children. In this Series paper, we summarise knowledge on the epidemiology, natural history, and treatment of chronic HBV infection in adolescents and children, and we highlight key differences from HBV infection in adults. The estimated global prevalence of HBV infection in children aged 5 years or younger is 1·3%. Most children are in the high-replication, low-inflammation phase of infection, with normal or only slightly raised aminotransferases; cirrhosis and hepatocellular carcinoma are rare. Although entecavir is approved and recommended for children aged 2–17 years, and tenofovir for those aged 12–18 years, a conservative approach to treatment initiation in children is recommended. Key actions to address current policy gaps include: validation of non-invasive tests for liver disease staging; additional immunopathogenesis studies in children with HBV infection; long-term follow-up of children on nucleoside or nucleotide analogue regimens to inform guidance on when to start treatment; evaluation of different treatment strategies for children with high rates of HBV replication; and establishment of paediatric treatment registries and international consortia to promote collaborative research
<i>Mycobacterium tuberculosis</i> infection among persons who inject drugs in San Diego, California
No full textBACKGROUND: Persons who inject drugs (PWID) might be at increased risk for Mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (LTBI) due to their injection drug use.
OBJECTIVES: To determine prevalence and correlates of M. tuberculosis infection among PWID in San Diego, California, USA.
METHODS: PWID aged 18 years underwent standardized interviews and serologic testing using an interferon-gamma release assay (IGRA) for LTBI and rapid point-of-care assays for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Independent correlates of M. tuberculosis infection were identified using multivariable log-binomial regression.
RESULTS: A total of 500 participants met the eligibility criteria. The mean age was 43.2 years (standard deviation 11.6); most subjects were White (52%) or Hispanic (30.8%), and male (75%). Overall, 86.7% reported having ever traveled to Mexico. Prevalence of M. tuberculosis infection was 23.6%; 0.8% were co-infected with HIV and 81.7% were co-infected with HCV. Almost all participants (95%) had been previously tested for M. tuberculosis; 7.6% had been previously told they were infected. M. tuberculosis infection was independently associated with being Hispanic, having longer injection histories, testing HCV-positive, and correctly reporting that people with 'sleeping' TB cannot infect others.
CONCLUSIONS: Strategies are needed to increase awareness about and treatment for M. tuberculosis infection among PWID in the US/Mexico border region
Adherence to Nucleos(t)ide Analogue Therapies for Chronic Hepatitis B Infection: A Systematic Review and Meta-Analysis
No full textSuccessful treatment outcomes for chronic hepatitis B virus (HBV) infection requires high levels of adherence to treatment. We searched three databases and abstracts from two conferences up to January 2018 for studies reporting the proportion of patients who were adherent to HBV antiviral therapy and pooled data using random effects meta-analysis. We included 30 studies, providing data for 23,823 patients. Overall, adherence to treatment was 74.6% (95% confidence interval [CI] 67.1%-82.1%). Adherence was similar in high-income settings (75.1%; 95% CI, 65.4%-85.0%) and in low-income and middle-income settings (72.9%; 95% CI, 57.8%-88.0%). Reported barriers to adherence included forgetting, limited understanding of the importance of adherence, and change to routine. \ud
Conclusion\ud
: There is a need to reinforce assessment and reporting of adherence as a routine part of HBV care and to assess the extent to which evidence-based interventions to improve adherence to medication for human immunodeficiency virus [HIV] and other chronic diseases are effective for HBV infection
Placental Malaria and Mother-to-Child Transmission of Human Immunodeficiency Virus-1 in Rural Rwanda
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