Economic evaluation alongside a single RCT of an integrative psychotherapeutic nursing home programme

__Abstract__ There is an 80% prevalence of two or more psychiatric symptoms in psychogeriatric patients. Multiple psychiatric symptoms (MPS) have many negative effects on quality of life of the patient as well as on caregiver burden and competence. Irrespective of the effectiveness of an intervention programme, it is important to take into account its economic aspects

A Systematic Review of Cost-of-Illness Studies of Multimorbidity

Objectives: The economic burden of multimorbidity is considerable. This review analyzed the methods of cost-of-illness (COI) studies and summarized the economic outcomes of multimorbidity. Methods: A systematic review (2000–2016) was performed, which was registered with Prospero, reported according to PRISMA, and used a quality checklist adapted for COI studies. The inclusion criteria were peer-reviewed COI studies on multimorbidity, whereas the exclusion criterion was studies focusing on an index disease. Extracted data included the definition, measure, and prevalence of multimorbidity; the number of included health conditions; the age of study population; the variables used in the COI methodology; the percentage of multimorbidity vs. total costs; and the average costs per capita. Results: Among the 26 included articles, 14 defined multimorbidity as a simple count of 2 or more conditions. Methodologies used to derive the costs were markedly different. Given different healthcare systems, OOP payments of multimorbidity varied across countries. In the 17 and 12 studies with cut-offs of ≥2 and ≥3 conditions, respectively, the ratios of multimorbidity to non-multimorbidity costs ranged from 2–16 to 2–10. Among the ten studies that provided cost breakdowns, studies with and without a societal perspective attributed the largest percentage of multimorbidity costs to social care and inpatient care/medicine, respectively. Conclusion: Multimorbidity was associated with considerable economic burden. Synthesising the cost of multimorbidity was challenging due to multiple definitions of multimorbidity and heterogeneity in COI methods. Count method was most popular to define multimorbidity. There is consistent evidence that multimorbidity was associated with higher costs

How to Appropriately Extrapolate Costs and Utilities in Cost-Effectiveness Analysis

Costs and utilities are key inputs into any cost-effectiveness analysis. Their estimates are typically derived from individual patient-level data collected as part of clinical studies the follow-up duration of which is often too short to allow a robust quantification of the likely costs and benefits a technology will yield over the patient’s entire lifetime. In the absence of long-term data, some form of temporal extrapolation—to project short-term evidence over a longer time horizon—is required. Temporal extrapolation inevitably involves assumptions regarding the behaviour of the quantities of interest beyond the time horizon supported by the clinical evidence. Unfortunately, the implications for decisions made on the basis of evidence derived following this practice and the degree of uncertainty surrounding the validity of any assumptions made are often not fully appreciated. The issue is compounded by the absence of methodological guidance concerning the extrapolation of non-time-to-event outcomes such as costs and utilities. This paper considers current approaches to predict long-term costs and utilities, highlights some of the challenges with the existing methods, and provides recommendations for future applications. It finds that, typically, economic evaluation models employ a simplistic approach to temporal extrapolation of costs and utilities. For instance, their parameters (e.g. mean) are typically assumed to be homogeneous with respect to both time and patients’ characteristics. Furthermore, costs and utilities have often been modelled to follow the dynamics of the associated time-to-event outcomes. However, cost and utility estimates may be more nuanced, and it is important to ensure extrapolation is carried out appropriately for these parameters

delta-L-(alpha-aminoadipoyl)-L-cysteinyl-D-valine synthetase: the order of peptide bond formation and timing of the epimerisation reaction.

delta-L-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase catalyses the formation of the common precursor tripeptide of both the penicillin and cephalosporin antibiotics from the L-enantiomers of its constituent amino acids. Replacement of cysteine with L-O-methylserine in preparative-scale incubations led to the isolation of both L-O-methylserinyl-L-valine and L-O-methylserinyl-D-valine dipeptides. The dipeptides were characterized with the aid of authentic synthetic standards by both 1H NMR and electrospray ionization MS. A revised mechanism for ACV biosynthesis involving formation of the cysteinyl-valine peptide bond before the epimerisation of valine and subsequent condensation with the delta-carboxyl of L-alpha-aminoadipate is therefore proposed

L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine synthetase: thioesterification of valine is not obligatory for peptide bond formation.

L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-valine (ACV) synthetase is probably the simplest known peptide synthetase in terms of the number of reactions catalyzed. In the "thiol-template" proposal for nonribosomal peptide synthesis, a key step is transfer of aminoacyl groups derived from the substrates to enzyme-bound thiols prior to peptide bond formation. No incorporation of 18O was seen in AMP isolated from the reaction mixture when di[18O]valine was incubated with relatively large amounts of active synthetase and MgATP. We therefore utilized di[18O]valine as a substrate for the biosynthesis of the diastereomeric dipeptides L-O-(methylserinyl)-L-valine and L-O-(methylserinyl)-D-valine [Shiau, C.-Y., Baldwin, J. E., Byford, M. F., Sobey, W. J., and Schofield, C. J. (1995) FEBS Lett. 358, 97-100]. In the L-O-(methylserinyl)-L-valine product, no significant loss of 18O was observed. However, in the L-O-(methylserinyl)-D-valine product, a significant loss of one or both 18O labels was observed. Thus, both peptide bond formation and the epimerization of the valine residue can both occur before formation of any thioester bond to the valine carboxylate in the biosynthesis of these dipeptides. The usual qualitative test for thioesterification of substrates to the synthetase, lability of enzyme-bound radiolabeled amino acid to performic acid, proved inconclusive in our hands. These results require a new mechanism for the enzymic synthesis of L-O-(methylserinyl)-L-valine and L-O-(methylserinyl)-D-valine and imply that a revised mechanism for ACV synthesis is also required