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Hepatitis B virus (HBV) infection remains a major public health problem and, in associated co-infection with hepatitis delta virus (HDV), causes the most severe viral hepatitis and accelerated liver disease progression. As a defective satellite RNA virus, HDV can only propagate in the presence of HBV infection, which makes HBV DNA and HDV RNA the standard biomarkers for monitoring the virological response upon antiviral therapy, in co-infected patients. Although assays have been described to quantify these viral nucleic acids in circulation independently, a method for monitoring both viruses simultaneously is not available, thus hampering characterization of their complex dynamic interactions. Here, we describe the development of a dual fluorescence channel detection system for pan-genotypic, simultaneous quantification of HBV DNA and HDV RNA through a one-step quantitative PCR. The sensitivity for both HBV and HDV is about 10 copies per microliter without significant interference between these two detection targets. This assay provides reliable detection for HBV and HDV basic research in vitro and in human liver chimeric mice. Preclinical validation of this system on serum samples from patients on or off antiviral therapy also illustrates a promising application that is rapid and cost-effective in monitoring HBV and HDV viral loads simultaneously.

Background & Aims: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs). Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR + NrtI, discontinued VBR only, or continued both VBR + NrtI. The primary efficacy endpoint was the proportion of patients with HBV DNA

Linezolid (LZD) has a longstanding reported association with the onset of serotonin toxicity (ST), secondary to drug–drug interactions with serotoninergic agents. There have been no conclusive data supporting the incidence or contributing risk factors to date. The study evaluated the incidence of ST in patients treated with LZD and serotonergic agents concomitantly versus LZD alone. The secondary objectives included a comparison of ST incidence in patients treated with one serotonergic agent + LZD versus two or more serotonergic agents + LZD. The studies used for this meta-analysis were retrieved from PubMed, Scopus, and Google Scholar. All studies including a comparison between LZD alone and LZD + a serotonergic agent published between 1 January 2000 and 1 October 2023 and meeting the quality standards were considered for inclusion. Fourteen studies were identified, with five meeting all inclusion and exclusion criteria with no significant heterogeneity. For the analysis of LZD monotherapy vs. SA combination therapy, four studies with 6025 patients total were analyzed and yielded an odds ratio of 1.78 (CI [1.04, 3.02]; I2 = 49%; GRADE certainty: low). Four studies and 2501 patients were included in the analysis of one versus more than one SA with an odds ratio of 5.18 (CI [1.05, 25.49]; I2 = 44.87; GRADE certainty: moderate). The Newcastle–Ottawa score, visual inspection of the funnel plot, and Egger’s statistic were used to evaluate quality and heterogeneity. The Peto method was used to calculate the summary odds ratios. All analyses were performed using Comprehensive Meta-Analysis version 3.0 and R, while GRADE was used to evaluate the quality of the final recommendation. The number of concomitant serotonergic agents may play a role in the development of serotonin toxicity in patients prescribed linezolid. In patients requiring linezolid therapy and serotonergic agents, risk versus benefit analysis should pay attention to the number of interacting drugs.

The purpose of this study was to investigate the effect of obesity on immunoglobulin G (IgG) pharmacokinetics in a rat model of obesity, and to collect clinical evidence for an association between the body composition and intravenous immune globulin (IVIG) pharmacokinetic parameters in humans. In a preclinical study, pharmacokinetics of human IgG was evaluated after intravenous (IV) and subcutaneous (SC) delivery to obese and lean rats (n = 6 in each group). Serial serum samples were analyzed using an ELISA. The animal body composition was assessed using computer tomography. Patients with primary immunodeficiency currently managed with IVIG, and at a steady state, were enrolled in the clinical study (n = 8). Serum immune globulin (Ig) concentrations were measured at baseline and immediately after the administration of two consecutive treatments, with an additional measurement at two weeks after the first administration. In addition to the patient demographic and clinical characteristics, body composition was measured using bioelectrical impedance analysis. The pharmacokinetics of human IgG was significantly different between the obese and lean rats after both the IV and SC administration of 0.5 g/kg. Furthermore, a significant difference in endogenous rat IgG was observed between the two strains. In the human study, total serum IgG and subtype (IgG1, IgG2, IgG3, IgG4) half-life negatively correlated with the body mass index and fat mass. The mean change in the total serum IgG concentration was significantly correlated to body mass index and fat mass. The results of the studies corroborated one another. In the animal study, most pharmacokinetic parameters of human IgG following IV and SC administration were significantly affected by obesity and changes in the body composition. In the clinical study, the mean serum IgG change after the IVIG administration strongly correlated to the BMI and body fat mass. Future studies are needed to establish the outcomes achieved with more frequent dosing in obese individuals with primary immunodeficiency.

Objectives: Levofloxacin and amiodarone are both known to prolong the QT interval. This study was conducted to estimate the risk of cardiac events in patients receiving concomitant levofloxacin and amiodarone. Methods: The study included patients who were admitted to a large academic community medical center from 1/2012 to 12/2015 and received both levofloxacin and amiodarone at some point during their hospitalization. Patients received concomitant or non-concomitant levofloxacin and amiodarone during hospitalization. The primary outcome was the occurrence of cardiac events during therapy. The secondary outcome was the proportion of patients with an electrocardiogram performed before and after initiation of therapy. Odds ratios for cardiac events were calculated using a multivariable logistic regression model with and without adjusting for the study variables. The concomitant group was further evaluated for predictors of the primary outcome using multivariable logistic regression. Results: This study included 240 patients, 164 (68.3%) of whom received concomitant levofloxacin and amiodarone. Concomitant medication therapy was associated with a greater than six-fold increased risk of cardiac events after adjusting for the study variables (Odds Ratio = 6.20; 95% Confidence Interval = 1.34–28.62). Conclusions: Patients receiving concomitant amiodarone and levofloxacin experienced a five-fold increase in cardiac events compared to patients given either medication alone. Keywords: Levofloxacin, Amiodarone, Cardiac risk, Cardiac death, QT interval

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused significant health and economic havoc around the globe. One of the early agents targeted for repurposing to treat and prevent COVID-19 was hydroxychloroquine (HCQ). In this systematic review and meta-analysis, HCQ is evaluated for its potential role in decreasing mortality in hospitalized patients with COVID-19. We searched PubMed, Web of Science, and medRxiv databases using combinations of the terms “COVID-19”, “SARS-CoV-2”, “coronavirus”, “hydroxychloroquine”, and “mortality”. Articles were selected for further review based on the content of their abstracts. Studies were excluded if they were of poor methodological quality, were not based in the inpatient setting, or did not have available data to assess the primary outcome of death between patients treated with HCQ versus standard of care. Once the final dataset was compiled, a meta-analysis using the random-effects model was performed. Our search identified 14 studies involving 24,780 patients of whom 12,707 patients were on HCQ alone or in combination with other adjuvant therapies. HCQ alone or in combination with other drugs did not significantly decrease mortality in hospitalized patients with COVID-19 (odds ratio [OR], 0.95; 95% CI, 0.72–1.26; p = 0.732; I2 = 91.05). Similar findings were observed in all subgroup analyses. HCQ did not significantly impact mortality in hospitalized patients with COVID-19. Additional well-designed studies are essential due to the heterogeneity in available studies.

We identified a 41.4% prevalence of hepatitis C virus, absence of HIV, and unexpectedly high frequency of hepatitis C virus genotype 3 among suburban New Jersey heroin users 17–35 years of age during 2014–2015. Despite 2 clinicians prepared to engage these users, few were successfully linked to care and treated.