Cost-Effectiveness of HBV and HCV Screening Strategies – A Systematic Review of Existing Modelling Techniques

Introduction

Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches.

Methods

A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions.

Results

The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology.

Conclusion

When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers.     

Harnessing Case Isolation and Ring Vaccination to Control Ebola

As a devastating Ebola outbreak in West Africa continues, non-pharmaceutical control measures including contact tracing, quarantine, and case isolation are being implemented. In addition, public health agencies are scaling up efforts to test and deploy candidate vaccines. Given the experimental nature and limited initial supplies of vaccines, a mass vaccination campaign might not be feasible. However, ring vaccination of likely case contacts could provide an effective alternative in distributing the vaccine. To evaluate ring vaccination as a strategy for eliminating Ebola, we developed a pair approximation model of Ebola transmission, parameterized by confirmed incidence data from June 2014 to January 2015 in Liberia and Sierra Leone. Our results suggest that if a combined intervention of case isolation and ring vaccination had been initiated in the early fall of 2014, up to an additional 126 cases in Liberia and 560 cases in Sierra Leone could have been averted beyond case isolation alone. The marginal benefit of ring vaccination is predicted to be greatest in settings where there are more contacts per individual, greater clustering among individuals, when contact tracing has low efficacy or vaccination confers post-exposure protection. In such settings, ring vaccination can avert up to an additional 8% of Ebola cases. Accordingly, ring vaccination is predicted to offer a moderately beneficial supplement to ongoing non-pharmaceutical Ebola control efforts.     

Heat Transfer Analysis for Stationary Boundary Layer Slip Flow of a Power-Law Fluid in a Darcy Porous Medium with Plate Suction/Injection

In this paper, we investigate the slip effects on the boundary layer flow and heat transfer characteristics of a power-law fluid past a porous flat plate embedded in the Darcy type porous medium. The nonlinear coupled system of partial differential equations governing the flow and heat transfer of a power-law fluid is transformed into a system of nonlinear coupled ordinary differential equations by applying a suitable similarity transformation. The resulting system of ordinary differential equations is solved numerically using Matlab bvp4c solver. Numerical results are presented in the form of graphs and the effects of the power-law index, velocity and thermal slip parameters, permeability parameter, suction/injection parameter on the velocity and temperature profiles are examined.     

Molecular Dynamic Simulations Reveal the Structural Determinants of Fatty Acid Binding to Oxy-Myoglobin

The mechanism(s) by which fatty acids are sequestered and transported in muscle have not been fully elucidated. A potential key player in this process is the protein myoglobin (Mb). Indeed, there is a catalogue of empirical evidence supporting direct interaction of globins with fatty acid metabolites; however, the binding pocket and regulation of the interaction remains to be established. In this study, we employed a computational strategy to elucidate the structural determinants of fatty acids (palmitic & oleic acid) binding to Mb. Sequence analysis and docking simulations with a horse (Equus caballus) structural Mb reference reveals a fatty acid-binding site in the hydrophobic cleft near the heme region in Mb. Both palmitic acid and oleic acid attain a “U” shaped structure similar to their conformation in pockets of other fatty acid-binding proteins. Specifically, we found that the carboxyl head group of palmitic acid coordinates with the amino group of Lys45, whereas the carboxyl group of oleic acid coordinates with both the amino groups of Lys45 and Lys63. The alkyl tails of both fatty acids are supported by surrounding hydrophobic residues Leu29, Leu32, Phe33, Phe43, Phe46, Val67, Val68 and Ile107. In the saturated palmitic acid, the hydrophobic tail moves freely and occasionally penetrates deeper inside the hydrophobic cleft, making additional contacts with Val28, Leu69, Leu72 and Ile111. Our simulations reveal a dynamic and stable binding pocket in which the oxygen molecule and heme group in Mb are required for additional hydrophobic interactions. Taken together, these findings support a mechanism in which Mb acts as a muscle transporter for fatty acid when it is in the oxygenated state and releases fatty acid when Mb converts to deoxygenated state.     

Degradation and Mineralization of Phenol Compounds with Goethite Catalyst and Mineralization Prediction Using Artificial Intelligence

The efficiency of phenol degradation via Fenton reaction using mixture of heterogeneous goethite catalyst with homogeneous ferrous ion was analyzed as a function of three independent variables, initial concentration of phenol (60 to 100 mg /L), weight ratio of initial concentration of phenol to that of H₂O₂ (1: 6 to 1: 14) and, weight ratio of initial concentration of goethite catalyst to that of H₂O₂ (1: 0.3 to 1: 0.7). More than 90 % of phenol removal and more than 40% of TOC removal were achieved within 60 minutes of reaction. Two separate models were developed using artificial neural networks to predict degradation percentage by a combination of Fe³⁺ and Fe²⁺ catalyst. Five operational parameters were employed as inputs while phenol degradation and TOC removal were considered as outputs of the developed models. Satisfactory agreement was observed between testing data and the predicted values (R² _Phenol = 0.9214 and R²TOC= 0.9082).     

Peripheral administration of oxytocin increases social affiliation in the naked mole-rat (Heterocephalus glaber)

The neuropeptide oxytocin regulates a wide variety of social behaviors across diverse species. However, the types of behaviors that are influenced by this hormone are constrained by the species in question and the social organization that a particular species exhibits. Therefore, the present experiments investigated behaviors regulated by oxytocin in a eusocial mammalian species by using the naked mole-rat (Heterocephalus glaber). In Experiment 1, adult non-breeding mole-rats were given intraperitoneal injections of either oxytocin (1 mg/kg or 10 mg/kg) or saline on alternate days. Animals were then returned to their colony and behavior was recorded for minutes 15–30 post-injection. Both doses of oxytocin increased huddling behavior during this time period. In Experiment 2, animals received intraperitoneal injections of either oxytocin (1 mg/kg), an oxytocin-receptor antagonist (0.1 mg/kg), a cocktail of oxytocin and the antagonist, or saline across 4 testing days in a counterbalanced design. Animals were placed in either a 2-chamber arena with a familiar conspecific or in a small chamber with 1 week old pups from their home colony and behaviors were recorded for minutes 15–30 post-injection. Oxytocin increased investigation of, and time spent in close proximity to, a familiar conspecific; these effects were blocked by the oxytocin antagonist. No effects were seen on pup-directed behavior. These data suggest that oxytocin is capable of modulating affiliative-like behavior in this eusocial species.     

Antagonism of Beclin 1‐dependent autophagy by BCL‐2 at the endoplasmic reticulum requires NAF‐1

In addition to mitochondria, BCL‐2 is located at the endoplasmic reticulum (ER) where it is a constituent of several distinct complexes. Here, we identify the BCL‐2‐interacting protein at the ER, nutrient‐deprivation autophagy factor‐1 (NAF‐1)—a bitopic integral membrane protein whose defective expression underlies the aetiology of the neurodegenerative disorder Wolfram syndrome 2 (WFS2). NAF‐1 contains a two iron–two sulphur coordinating domain within its cytosolic region, which is necessary, but not sufficient for interaction with BCL‐2. NAF‐1 is displaced from BCL‐2 by the ER‐restricted BH3‐only protein BIK and contributes to regulation of BIK‐initiated autophagy, but not BIK‐dependent activation of caspases. Similar to BCL‐2, NAF‐1 is found in association with the inositol 1,4,5‐triphosphate receptor and is required for BCL‐2‐mediated depression of ER Ca²⁺ stores. During nutrient deprivation as a physiological stimulus of autophagy, BCL‐2 is known to function through inhibition of the autophagy effector and tumour suppressor Beclin 1. NAF‐1 is required in this pathway for BCL‐2 at the ER to functionally antagonize Beclin 1‐dependent autophagy. Thus, NAF‐1 is a BCL‐2‐associated co‐factor that targets BCL‐2 for antagonism of the autophagy pathway at the ER.     

Organic acid production and plant growth promotion as a function of phosphate solubilization by Acinetobacter rhizosphaerae strain BIHB 723 isolated from the cold deserts of the trans-Himalayas

An efficient phosphate-solubilizing plant growth–promoting Acinetobacter rhizosphaerae strain BIHB 723 exhibited significantly higher solubilization of tricalcium phosphate (TCP) than Udaipur rock phosphate (URP), Mussoorie rock phosphate (MRP) and North Carolina rock phosphate (NCRP). Qualitative and quantitative differences were discerned in the gluconic, oxalic, 2-keto gluconic, lactic, malic and formic acids during the solubilization of various inorganic phosphates by the strain. Gluconic acid was the main organic acid produced during phosphate solubilization. Formic acid production was restricted to TCP solubilization and oxalic acid production to the solubilization of MRP, URP and NCRP. A significant increase in plant height, shoot fresh weight, shoot dry weight, root length, root dry weight, and root, shoot and soil phosphorus (P) contents was recorded with the inoculated treatments over the uninoculated NP₀K or NP_TCPK treatments. Plant growth promotion as a function of phosphate solubilization suggested that the use of bacterial strain would be a beneficial addition to the agriculture practices in TCP-rich soils in reducing the application of phosphatic fertilizers.     

Stem cell therapy in the inner ear: recent achievements and prospects

Because of its high prevalence and social impact, hearing impairment is a major public health problem. Whatever the cause--heredity, acoustic trauma, aminoglycoside antibiotics, noise exposure or aging--the hearing impairment is often caused by an irreversible loss of sensory hair cells. So far, hearing aids and cochlear implants are the only possibility to "treat" profound deafness. With the advent of regenerative medicine, extensive studies aimed to repair, regenerate or replace lost hair cells have been initiated. Recently, Stefan Heller and colleagues described a guidance protocol to induce mouse embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) to differentiate into mechanosensitive hair cells. The resulting hair cells hold promise as a tool for hair cell molecular physiology and physiopathology, drug discovery, and possibly also hair cell replacement. The next challenges, alternative strategies, their limitations and prospects are also discussed.