Developing a risk prediction model for 30-Day unplanned hospitalisation in patients receiving outpatient parenteral antimicrobial therapy

Objectives Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat a wide range of infections. However, there is risk of hospital readmissions. The study aim was to develop a prediction model for the risk of 30-day unplanned hospitalisation in patients receiving OPAT. Methods Using a retrospective cohort design, we retrieved data on 1073 patients who received OPAT over two years (01/2015 - 01/2017) at a large teaching hospital in Sheffield, UK. We developed a multivariable logistic regression model for 30-day unplanned hospitalisation and assessed its discrimination and calibration abilities, and internally validated using bootstrap resampling. Results The 30-day unplanned hospitalisation rate was 11% (123/1073). The main indication for hospitalisation was worsening or non-response of infection (42%; 52/123). The final regression model consisted of age (adjusted odds ratio [aOR], 1.18 per decade; 95% confidence interval [CI], 1.04-1.34), Charlson comorbidity score (aOR, 1.11 per unit increase; 95%CI, 1.00-1.23), prior hospitalisations in past 12 months (aOR, 1.30 per admission; 95%CI, 1.17-1.45), concurrent intravenous antimicrobial therapy (aOR, 1.89; 95%CI, 1.03-3.47), and endovascular infection (aOR, 3.51; 95%CI, 1.49-8.28). Mode of OPAT treatment was retained in the model as a confounder. The model had adequate concordance (c-statistic 0.72; 95%CI 0.67-0.77) and calibration (Hosmer-Lemeshow P=0.546; calibration slope 0.99; 95%CI 0.78-1.21) and low degree of optimism (bootstrap optimism corrected c-statistic, 0.70). Conclusions We identified a set of six important predictors of unplanned hospitalisation based on readily available data. The prediction model may help improve OPAT outcomes through better identification of high-risk patients and provision of tailored care

Dynamics of Hepatitis B Virus Quasispecies in Association with Nucleos(t)ide Analogue Treatment Determined by Ultra-Deep Sequencing

[Background and Aims]: Although the advent of ultra-deep sequencing technology allows for the analysis of heretofore-undetectable minor viral mutants, a limited amount of information is currently available regarding the clinical implications of hepatitis B virus (HBV) genomic heterogeneity. [Methods]: To characterize the HBV genetic heterogeneity in association with anti-viral therapy, we performed ultra-deep sequencing of full-genome HBV in the liver and serum of 19 patients with chronic viral infection, including 14 therapy-naïve and 5 nucleos(t)ide analogue(NA)-treated cases. [Results]: Most genomic changes observed in viral variants were single base substitutions and were widely distributed throughout the HBV genome. Four of eight (50%) chronic therapy-naïve HBeAg-negative patients showed a relatively low prevalence of the G1896A pre-core (pre-C) mutant in the liver tissues, suggesting that other mutations were involved in their HBeAg seroconversion. Interestingly, liver tissues in 4 of 5 (80%) of the chronic NA-treated anti-HBe-positive cases had extremely low levels of the G1896A pre-C mutant (0.0%, 0.0%, 0.1%, and 1.1%), suggesting the high sensitivity of the G1896A pre-C mutant to NA. Moreover, various abundances of clones resistant to NA were common in both the liver and serum of treatment-naïve patients, and the proportion of M204VI mutants resistant to lamivudine and entecavir expanded in response to entecavir treatment in the serum of 35.7% (5/14) of patients, suggesting the putative risk of developing drug resistance to NA. [Conclusion]: Our findings illustrate the strong advantage of deep sequencing on viral genome as a tool for dissecting the pathophysiology of HBV infection

Hepatitis B virus genotypes and evolutionary profiles from blood donors from the northwest region of China

Hepatitis B virus (HBV) is prevalent in China and screening of blood donors is mandatory. Up to now, ELISA has been universally used by the China blood bank. However, this strategy has sometimes failed due to the high frequency of nucleoside acid mutations. Understanding HBV evolution and strain diversity could help devise a better screening system for blood donors. However, this kind of information in China, especially in the northwest region, is lacking. In the present study, serological markers and the HBV DNA load of 11 samples from blood donor candidates from northwest China were determined. The HBV strains were most clustered into B and C genotypes and could not be clustered into similar types from reference sequences. Subsequent testing showed liver function impairment and increasing virus load in the positive donors. This HBV evolutionary data for China will allow for better ELISA and NAT screening efficiency in the blood bank of China, especially in the northwest region

In vitro hepatitis C virus replication systems and novel therapeutic agents for chronic hepatitis C

Until recently, due to the lack of an effective cell culture system for the Hepatitis C Virus (HCV), the design of novel therapeutic agents was difficult. The recent progress in the molecular virology of HCV has created the appropriate conditions for the development of in vitro viral replication systems and has led to research that was previously impossible. The first viral replication systems (replicons) were subgenomic, while currently full-length replicons are available. A full-length HCV genome that replicates and produces virus particles that are infectious in cell culture (HCVcc) has allowed the study of the natural characteristics of HCV. Up until the present, recombinant Interferon (IFN) a-2a, a-2b and pegylated interferon (PEG-IFN) alone or in combination with ribavirin have been the only approved available treatments. Serious side-effects and low efficacy of the current treatments, along with high prevalence of the infection worldwide mandate that new therapeutic agents need to be developed. NS3 protease, responsible for the release of non-structural viral proteins, and RNA-dependent-RNA-polymerase (RdRp) of NS5B are potential targets. Apart from the NS protease inhibitors other compounds play a significant rote in the treatment of HCV infection, among which cyclosporin A, albuferon, merimepodib or VX-497, viramidin, arsenic trioxide (ATO), sodium stibogluconate (SSG) and interleukins 28 (IL-28) and 29 (IL-29) are examples

Analysing the evolutionary history of HCV: Puzzle of ancient phylogenetic discordance

Though recombination is an important evolutionary strategy in RNA viruses, only two cases of HCV recombinant strains have been reported. Our objective was to analyze the evolutionary history of the HCV genotypes aiming to obtain evidence of significant phylogenetic discordance due to either recombination or selective forces leading to convergent/divergent evolution. The data support an evolutionary preservation of the interferon-resistance related genomic region (ISDR) for the genotypes 1 and 4. On the other hand, there was no evidence that recombination has occurred in the past with the possible exception of genotype 4. Moreover, it is evidenced that genotypes 3 and 10 split more recently than genotypes 6-9 and 11. This analysis reverberates a commonly found pattern in rapidly evolving viruses, that is the strongly disturbed evolutionary history which deforms the uniform distribution of the phylogenetic relationships across the genome, and introduces a conservative inference framework for approaching this kind of data. © 2006 Elsevier B.V. All rights reserved

Analysing the evolutionary history of HCV: puzzle of ancient phylogenetic discordance.

Though recombination is an important evolutionary strategy in RNA viruses, only two cases of HCV recombinant strains have been reported. Our objective was to analyze the evolutionary history of the HCV genotypes aiming to obtain evidence of significant phylogenetic discordance due to either recombination or selective forces leading to convergent/divergent evolution. The data support an evolutionary preservation of the interferon-resistance related genomic region (ISDR) for the genotypes 1 and 4. On the other hand, there was no evidence that recombination has occurred in the past with the possible exception of genotype 4. Moreover, it is evidenced that genotypes 3 and 10 split more recently than genotypes 6-9 and 11. This analysis reverberates a commonly found pattern in rapidly evolving viruses, that is the strongly disturbed evolutionary history which deforms the uniform distribution of the phylogenetic relationships across the genome, and introduces a conservative inference framework for approaching this kind of data

Clinical efficacy, cost-analysis and patient acceptability of outpatient parenteral antibiotic therapy (OPAT): a decade of Sheffield (UK) OPAT service

Outpatient parenteral antimicrobial therapy (OPAT) has evolved relatively slowly in the UK. This study describes the OPAT service based in a large UK teaching hospital in Sheffield, and examines the clinical efficacy, patient acceptability and costs saved over a 10-year period. Data on 3812 episodes of OPAT treatment administered between January 2006 and January 2016 were retrieved from a prospectively maintained electronic database. We compared the real costs of the OPAT service with estimated costs of conventional inpatient care for these patient episodes. We also analysed patient feedback questionnaires that were randomly administered between January 2014 and January 2015. A wide range of infections were managed during the 10-year period. Skin and soft tissue infections accounted for 57% of OPAT episodes. The total number of bed days saved was 49854. A successful outcome (cure or improvement) was found in 3357 (88%) episodes. Readmission occurred in 265 (7%) episodes. The rates of healthcare-associated infections were low: 15 intravenous line-related infections were recorded (0.3 per 1000 OPAT patient days). Patient acceptance and satisfaction with OPAT were high. OPAT cost 15%, 39%, 40% and 44% of inpatient costs respectively for an infectious diseases unit, national average costs, for other departments (non-infectious diseases unit), and the minimum national average costs for each diagnostic category. This study shows that OPAT is safe, clinically efficacious and acceptable for treating a wide range of infections with high levels of patient satisfaction and substantial cost savings

Aseptic meningitis with urinary retention: A case report

Introduction. Aseptic meningitis is serious inflammation of the meninges caused by agents including viruses, non-viral pathogens, non-infectious conditions and chemicals. Case Presentation. This study concerns the case of a 16-year-old healthy Greek female with persistent fever, mild headache and acute urinary retention, secondary to aseptic meningitis. Physical examination revealed no distinct signs of meningeal irritation. The urinary bladder was palpable, painless and over-distended. Serology carried out for common viruses was as follows: CMV IgG (), CMV IgM (), HSV IgG (), HSV IgM (+), VZ IgG (+), VZ IgM (), EBV IgG () and EBV IgM (+). During recovery in hospital, three trials of removing a urinary catheter were carried out; during the first two attempts the patient was unable to urinate and had a loss of bladder sensation. On the third attempt the patient had modest bladder perception but she left a post-voiding residual, and was instructed to perform bladder self-catheterization. Seven days after being discharged the patient underwent a full recovery. Conclusion. There are few reports concerning aseptic meningitis together with acute urinary retention. A number of these cases concern so-called meningitis-retention syndrome, which implies an underlying CNS mechanism, while others concerned an underlying peripheral nervous system mechanism. © Copyright 2011 Fotinie Ntziora et al