Receiver operating characteristic curves and confidence bands for support vector machines.

Many problems that appear in biomedical decision-making, such as diagnosing disease and predicting response to treatment, can be expressed as binary classification problems. The support vector machine (SVM) is a popular classification technique that is robust to model misspecification and effectively handles high-dimensional data. The relative costs of false positives and false negatives can vary across application domains.

No Association Between DAA Treatment for HCV Infection and Herpes Zoster Infection in Analysis of Data From 37 Clinical Trials.

Background And Aims: Recent case series and retrospective studies have raised concerns that patients who receive direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection are at increased risk of developing varicella-zoster virus infection (VZV reactivation). We investigated the relationship between DAA treatment and VZV reactivation by analyzing pooled participant-level data from 37 clinical trials of DAA agents.

Methods: We obtained demographic, adverse event, and laboratory data from 13,816 participants in 37 clinical trials submitted to the Food and Drug Administration for approval of DAA agents for treatment of HCV infection.

Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy.

Background: Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown.

Methods: We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype.

Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference.

The International Society for Influenza and other Respiratory Virus Diseases held its 6th Antiviral Group (isirv-AVG) conference in Rockville, Maryland, November 13-15, 2018. The three-day program was focused on therapeutics towards seasonal and pandemic influenza, respiratory syncytial virus, coronaviruses including MERS-CoV and SARS-CoV, human rhinovirus, and other respiratory viruses. Updates were presented on several influenza antivirals including baloxavir, CC-42344, VIS410, immunoglobulin, immune plasma, MHAA4549A, pimodivir (JNJ-63623872), umifenovir, and HA minibinders; RSV antivirals including presatovir (GS-5806), ziresovir (AK0529), lumicitabine (ALS-008176), JNJ-53718678, JNJ-64417184, and EDP-938; broad spectrum antivirals such as favipiravir, VH244, remdesivir, and EIDD-1931/EIDD-2801; and host directed strategies including nitazoxanide, eritoran, and diltiazem.

Immunological recovery in T-cell activation after sustained virologic response among HIV positive and HIV negative chronic Hepatitis C patients.

Background: Rapid decreases in activated CD4+ and CD8+ (HLA-DR + and CD38+ co-expressed) T-lymphocytes have been described within 1-2 weeks of initiating direct-acting antiviral (DAA) therapy among chronic Hepatitis C (CHC) patients. However, it is not known whether these changes are maintained past sustained virologic response (SVR), particularly in those who are HIV/HCV-coinfected.

Methods: We investigated the changes in immune parameters of T-lymphocytes from pre-DAA therapy to post-SVR among HIV negative and HIV positive patients with CHC.

Brief Report: Body Mass Index and Cognitive Function Among HIV-1-Infected Individuals in China, India, and Nigeria.

Background: Risk of cognitive impairment is increased among persons with high or low body mass index in HIV- and HIV+ populations in resource-rich settings. We examined this association among HIV+ patients in 3 resource-limited settings.

Methods: This secondary analysis included data of 761 HIV+ volunteers pooled from 3 prospective cohort studies conducted in China (n = 404; 53%), India (n = 200; 26%), and Nigeria (n = 157; 21%).

Demography and the dual epidemics of tuberculosis and HIV: Analysis of cross-sectional data from Sub-Saharan Africa.

Background: Convergence of tuberculosis (TB) and HIV epidemics is associated with higher morbidity and mortality risks and understanding their distribution across key demographic factors is essential for prevention and control. This analysis examines the prevalence of TB, HIV and TB-HIV coinfection across age and gender in patients with presumptive TB seeking care at the National TB and Leprosy Training Center in Nigeria.

Methods: Samples from 1603 presumptive pulmonary TB cases who provided informed consent were evaluated with a sequential testing algorithm that included a smear microscopy, cultures in liquid and broth media and then genotyping by Hain line probe assays.

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria.

Plasma HIV RNA level has been shown to correlate with HIV disease progression, morbidity, and mortality. We examined the association between levels of plasma HIV RNA and cognitive function among patients in Nigeria. A total of 179 HIV-1-infected participants with available plasma HIV RNA results and followed longitudinally for up to 2 years were included in this study.

Risk-Based Hepatitis C Screening in Pregnancy Is Less Reliable Than Universal Screening: A Retrospective Chart Review.

Current guidelines recommend only hepatitis C virus (HCV) risk-based screening during pregnancy. We examined screening practices at a major medical center and found inconsistent risk-based screening and the presence of HCV among women with no known risk factors. We make a case for the implementation of universal HCV screening during pregnancy.

Cognitive Function Among Antiretroviral Treatment-Naive Individuals Infected With Human Immunodeficiency Virus Type 1 Subtype G Versus CRF02_AG in Nigeria.

Background: Human immunodeficiency virus type 1 (HIV-1) subtype has been shown to be associated with disease progression. We compared cognitive function between individuals infected with HIV-1 subtype G and CRF02_AG in Nigeria.

Methods: For this cross-sectional study, samples were analyzed from 146 antiretroviral-naive participants.

In vitro-in vivo correlations for nicotine transdermal delivery systems evaluated by both in vitro skin permeation (IVPT) and in vivo serum pharmacokinetics under the influence of transient heat application.

The in vitro permeation test (IVPT) has been widely used to characterize the bioavailability (BA) of compounds applied on the skin. In this study, we performed IVPT studies using excised human skin (in vitro) and harmonized in vivo human serum pharmacokinetic (PK) studies to evaluate the potential in vitro-in vivo correlation (IVIVC) of nicotine BA from two, matrix-type, nicotine transdermal delivery systems (TDS). The study designs used for both in vitro and in vivo studies included 1h of transient heat (42±2°C) application during early or late time periods post-dosing.

Immunologic response to antiretroviral therapy by age among treatment-naive patients in Sub-Saharan Africa.

Objective: To estimate the association between age at antiretroviral therapy (ART) initiation and immunologic response over time by stratum of baseline CD4 cell counts.

Design: Retrospective cohort analysis of data pooled from four President's Emergency Plan for AIDS Relief funded countries in Sub-Saharan Africa.

Methods: General linear models were used to estimate the mean CD4 cell count by age group within groups defined by baseline CD4 cell count.

Spontaneous Viral Load Decline and Subsequent Clearance of Chronic Hepatitis C Virus in Postpartum Women Correlates With Favorable Interleukin-28B Gene Allele.

Background: Postpartum hepatitis C viral (HCV) load decline followed by spontaneous clearance has been previously described. Herein we identify predictors for viral decline in a cohort of HCV-infected postpartum women.

Methods: Pregnant women at Cairo University were screened for anti-HCV antibodies and HCV RNA, and viremic women were tested for quantitative HCV RNA at 3, 6, 9, and 12 months postpartum.

Tularemia vaccine: Safety, reactogenicity, "Take" skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain - A phase 2 randomized clinical Trial.

Background: Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices.

Methods: A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS).

Perinatal HIV Infection and Exposure and Their Association With Dental Caries in Nigerian Children.

Background: Although HIV infection is associated with well-known oral pathologies, there remains a dearth of comparative studies aimed at determining the association between HIV infection/exposure and early childhood caries.

Methods: This is a cross-sectional study using a convenience sample of 3 groups of children receiving care at a tertiary care hospital in Nigeria. The groups include HIV infected (HI), HIV exposed but uninfected and HIV-unexposed and -uninfected children 6 through 72 months of age.

Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria.

Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants.

Assessing the Awareness of Egyptian Medical Students about Responsible Conduct of Research and Research Ethics: Impact of an Educational Campaign.

This is a quasi-experimental pre-post assessment study utilizing an anonymous self-administered questionnaire to assess Egyptian medical students' awareness about responsible conduct of research (RCR) and research ethics. Students' were assessed before and after an RCR awareness campaign. Our results showed that most of the pre-campaign respondents were not familiar with the basic principles and terms of RCR.

Hepatitis C Virus (HCV) Vertical Transmission in 12-Month-Old Infants Born to HCV-Infected Women and Assessment of Maternal Risk Factors.

Background.  Hepatitis C virus (HCV) is an underappreciated cause of pediatric liver disease, most frequently acquired by vertical transmission (VT). Current guidelines that include the option of screening infants for HCV RNA at 1-2 months are based on data prior to current real-time polymerase chain reaction (PCR)-based testing.

Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects.

Background: Modified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1×10(8) TCID50 in a volume of 0.5mL. This study compared the safety and immunogenicity of the standard formulation, dose and route with both a more stable, lyophilized formulation and with an antigen-sparing intradermal (ID) route of administration.

Safety and Immunogenicity of a Single Low Dose or High Dose of Clade 2 Influenza A(H5N1) Inactivated Vaccine in Adults Previously Primed With Clade 1 Influenza A(H5N1) Vaccine.

Influenza A(H5N1) vaccination strategies that improve the speed of the immunological response and cross-clade protection are desired. We compared the immunogenicity of a single 15-μg or 90-μg dose of A/H5N1/Indonesia/05/05 (clade 2) vaccine in adults who were previously primed with A/H5N1/Vietnam/1203/2004 (clade 1) vaccine. High-dose vaccine resulted in significantly higher titers to both clade 1 and 2 antigens.

Reliability of risk-based screening for hepatitis C virus infection among pregnant women in Egypt.

Objectives: The Centers for Disease Control and Prevention (CDC) only recommends risk-based HCV screening for pregnant women in the United States. This study sought to determine the reliability of risk-based versus universal HCV screening for pregnant women in Egypt, a country with the world's highest HCV prevalence that also relies on risk-based screening, and to identify additional characteristics that could increase the reliability of risk-based screening.

Methods: Pregnant women attending the Cairo University antenatal clinic were tested for anti-HCV antibodies and RNA, and demographic characteristics and risk factors for infection were assessed.

Cost-effectiveness of point-of-care digital chest-x-ray in HIV patients with pulmonary mycobacterial infections in Nigeria.

Background: Chest-x-ray is routinely used in the diagnosis of smear negative tuberculosis (TB). This study assesses the incremental cost per true positive test of a point-of-care digital chest-x-ray, in the diagnosis of pulmonary mycobacterial infections among HIV patients with presumed tuberculosis undetected by smear microscopy.

Methods: Consecutive patients with clinical suspicion of pulmonary tuberculosis were serially tested for Human immunodeficiency virus (HIV), their sputum examined for Acid Fast Bacilli then cultured in broth and solid media.

From intense rejection to advocacy: how Muslim clerics were engaged in a polio eradication initiative in Northern Nigeria.

Gambo Aliyu and colleagues describe an approach to eradicating polio in Northern Nigeria by engaging Muslim clerics in influencing community perceptions. Please see later in the article for the Editors' Summary.

Long-term influence of chemotherapy on steatosis-associated advanced hepatic fibrosis.

To determine whether chemotherapy treatment at least 6 months prior to the detection of hepatic steatosis is associated with advanced hepatic fibrosis. Demographics, comorbid conditions, and laboratory data for cancer patients with hepatic steatosis were reviewed. The primary end point of this study was a low probability of fibrosis as calculated by the AST-to-platelet ratio index (APRI)-a surrogate for the absence of histologic bridging fibrosis and/or cirrhosis.