Capturing Budget Impact Considerations Within Economic Evaluations: A Systematic Review of Economic Evaluations of Rotavirus Vaccine in Low- and Middle-Income Countries and a Proposed Assessment Framework.

BACKGROUND: In low- and middle-income countries, budget impact is an important criterion for funding new interventions, particularly for large public health investments such as new vaccines. However, budget impact analyses remain less frequently conducted and less well researched than cost-effectiveness analyses. OBJECTIVE: The objective of this study was to fill the gap in research on budget impact analyses by assessing (1) the quality of stand-alone budget impact analyses, and (2) the feasibility of extending cost-effectiveness analyses to capture budget impact. METHODS: We developed a budget impact analysis checklist and scoring system for budget impact analyses, which we then adapted for cost-effectiveness analyses, based on current International Society for Pharmacoeconomics and Outcomes Research Task Force recommendations. We applied both budget impact analysis and cost-effectiveness analysis checklists and scoring systems to examine the extent to which existing economic evaluations provide sufficient evidence about budget impact to enable decision making. We used rotavirus vaccination as an illustrative case in which low- and middle-income countries uptake has been limited despite demonstrated cost effectiveness. A systematic literature review was conducted to identify economic evaluations of rotavirus vaccine in low- and middle-income countries published between January 2000 and February 2017. We critically appraised the quality of budget impact analyses, and assessed the extension of cost-effectiveness analyses to provide useful budget impact information. RESULTS: Six budget impact analyses and 60 cost-effectiveness analyses were identified. Budget impact analyses adhered to most International Society for Pharmacoeconomics and Outcomes Research recommendations, with key exceptions being provision of undiscounted financial streams for each budget period and model validation. Most cost-effectiveness analyses could not be extended to provide useful budget impact information; cost-effectiveness analyses also rarely presented undiscounted annual costs, or estimated financial streams during the first years of programme scale-up. CONCLUSIONS: Cost-effectiveness analyses vastly outnumber budget impact analyses of rotavirus vaccination, despite both being critical for policy decision making. Straightforward changes to the presentation of cost-effectiveness analyses results could facilitate their adaptation into budget impact analyses

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Determination of boron in serum, plasma and urine by inductively coupled plasma mass spectrometry (ICP-MS). Use of mannitol-ammonia as diluent and for eliminating memory effect

A rapid and accurate method has been developed for the determination of boron in serum, plasma and urine by inductively coupled plasma mass spectrometry. The memory effects of B were examined using different diluents/rinse solutions, including water, nitric acid, Triton X-100, ammonia and mannitol in water, in nitric acid and in ammonia. A combination of ammonia with mannitol, as both diluent and flush solution, gave the best precision, the minimum memory effect and the lowest background. A sample dilution of 20-fold was simply made for serum and plasma and 100-fold for urine for determination with a single calibration curve. Beryllium was employed as the internal standard to control matrix effects and to compensate for possible fluctuation and instrument drift. The isotope B-10(+) was utilised to avoid spectral overlap by the intense C-12(+) isotope. The final solution of blank, standards and samples contained 0.25% w/v mannitol, 0.1 M ammonia and 20 ng ml(-1) of Be. Six samples, including human and horse serum, human and horse plasma, and human urine, were analysed to test the reliability of the method. A limit of detection (3 sigma) of 0.015 ng ml(-1) was obtained and the recoveries of spiked boron (two spiking levels for each matrix) from the selected samples ranged from 98% to 104%. Much higher concentrations of B in urine (approximate to 1 mu g ml(-1)) were found compared to those in serum and plasma samples (32.8-61.1 ng ml(-1))

Entering and Exiting the Medicare Part D Coverage Gap: Role of Comorbidities and Demographics

Background: Some Medicare Part D enrollees whose drug expenditures exceed a threshold enter a coverage gap with full cost-sharing, increasing their risk for reduced adherence and adverse outcomes. Objective: To examine comorbidities and demographic characteristics associated with gap entry and exit. Design: We linked 2005-2006 pharmacy, outpatient, and inpatient claims to enrollment and Census data. We used logistic regression to estimate associations of 2006 gap entry and exit with 2005 medical comorbidities, demographics, and Census block characteristics. We expressed all results as predicted percentages. PATIENTS: 287,713 patients without gap coverage, continuously enrolled in a Medicare Advantage Part D (MAPD) plan serving eight states. Patients who received a low-income subsidy, could not be geocoded, or had no 2006 drug fills were excluded. Results: Of enrollees, 15.9% entered the gap, 2.6% within the first 180 days; among gap enterers, only 6.7% exited again. Gap entry was significantly associated with female gender and all comorbidities, particularly dementia (39.5% gap entry rate) and diabetes (28.0%). Among dementia patients entering the gap, anti-dementia drugs (donepezil, memantine, rivastigmine, and galantamine) and atypical antipsychoticmedications (risperidone, quetiapine, and olanzapine) together accounted for 40% of pre-gap expenditures. Among diabetic patients, rosiglitazone accounted for 7.2% of pre-gap expenditures. Having dementia was associated with twice the risk of gap exit. Conclusions: Certain chronically ill MAPD enrollees are at high risk of gap entry and exposure to unsubsidized medication costs. Clinically vulnerable populations should be counseled on how to best manage costs through drug substitution or discontinuation of specific, non-essential medications. © 2010 Society of General Internal Medicine

Holocentric Chromosomes of Luzula elegans Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

The structure of holocentric chromosomes was analyzed in mitotic cells of Luzula elegans. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, L. elegans chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to Arabidopsis-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability. Copyright (C) 2011 S. Karger AG, Base

Building social capital through breastfeeding peer support: Insights from an evaluation of a voluntary breastfeeding peer support service in North-West England

Background: Peer support is reported to be a key method to help build social capital in communities. To date there are no studies that describe how this can be achieved through a breastfeeding peer support service. In this paper we present findings from an evaluation of a voluntary model of breastfeeding peer support in North-West England to describe how the service was operationalized and embedded into the community. This study was undertaken from May, 2012 to May, 2013. Methods: Interviews (group or individual) were held with 87 participants: 24 breastfeeding women, 13 peer supporters and 50 health and community professionals. The data contained within 23 monthly monitoring reports (January, 2011 to February 2013) compiled by the voluntary peer support service were also extracted and analysed. Results: Thematic analysis was undertaken using social capital concepts as a theoretical lens. Key findings were identified to resonate with ’bonding’, ‘bridging’ and ‘linking’ forms of social capital. These insights illuminate how the peer support service facilitates ‘bonds’ with its members, and within and between women who access the service; how the service ‘bridges’ with individuals from different interests and backgrounds, and how ‘links’ were forged with those in authority to gain access and reach to women and to promote a breastfeeding culture. Some of the tensions highlighted within the social capital literature were also identified. Conclusions: Horizontal and vertical relationships forged between the peer support service and community members enabled peer support to be embedded into care pathways, helped to promote positive attitudes to breastfeeding and to disseminate knowledge and maximise reach for breastfeeding support across the community. Further effort to engage with those of different ethnic backgrounds and to resolve tensions between peer supporters and health professionals is warranted

Capillary Electrophoresis Separation of Protein Composition of γ-Irradiated Food Pathogens Listeria monocytogenes and Staphylococcus aureus

which were previously treated at different irradiation doses., one protein (50 S ribosomal protein) with the MW of 16.3 kDa was significantly decreased at a low dose of irradiation treatment and the other protein (transcriptional regulator CtsR) with the MW of 17.7 kDa was increased significantly (P≤0.05) at all doses of irradiation treatment compared to control.. The research further confirmed that capillary electrophoresis is a useful method to separate and analyse proteins expression which may be related to the resistance or sensitivity of food pathogens to γ-irradiation

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n = 35), inflamed pleura (IP, n = 12) and uninflammed pleura (UP, n = 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P = 0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P = 0.03, total MMP-2 P = 0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM. © 2003 Cancer Research UK