Economic evaluation of a group-based exercise program for falls prevention among the older community-dwelling population

BACKGROUND: Falls among older people are of growing concern globally. Implementing cost-effective strategies for their prevention is of utmost importance given the ageing population and associated potential for increased costs of fall-related injury over the next decades. The purpose of this study was to undertake a cost-utility analysis and secondary cost-effectiveness analysis from a healthcare system perspective, of a group-based exercise program compared to routine care for falls prevention in an older community-dwelling population. METHODS: A decision analysis using a decision tree model was based on the results of a previously published randomised controlled trial with a community-dwelling population aged over 70. Measures of falls, fall-related injuries and resource use were directly obtained from trial data and supplemented by literature-based utility measures. A sub-group analysis was performed of women only. Cost estimates are reported in 2010 British Pound Sterling (GBP). RESULTS: The ICER of GBP£51,483 per QALY for the base case analysis was well above the accepted cost-effectiveness threshold of GBP£20,000 to £30,000 per QALY, but in a sensitivity analysis with minimised program implementation the incremental cost reached GBP£25,678 per QALY. The ICER value at 95% confidence in the base case analysis was GBP£99,664 per QALY and GBP£50,549 per QALY in the lower cost analysis. Males had a 44% lower injury rate if they fell, compared to females resulting in a more favourable ICER for the women only analysis. For women only the ICER was GBP£22,986 per QALY in the base case and was below the cost-effectiveness threshold for all other variations of program implementation. The ICER value at 95% confidence was GBP£48,212 in the women only base case analysis and GBP£23,645 in the lower cost analysis. The base case incremental cost per fall averted was GBP£652 (GBP£616 for women only). A threshold analysis indicates that this exercise program cannot realistically break even. CONCLUSIONS: The results suggest that this exercise program is cost-effective for women only. There is no evidence to support its cost-effectiveness in a group of mixed gender unless the costs of program implementation are minimal. Conservative assumptions may have underestimated the true cost-effectiveness of the program

Statistical modelling for falls count data

Falls and their injury outcomes have count distributions that are highly skewed toward the right with clumping at zero, posing analytical challenges. Different modelling approaches have been used in the published literature to describe falls count distributions, often without consideration of the underlying statistical and modelling assumptions. This paper compares the use of modified Poisson and negative binomial (NB) models as alternatives to Poisson (P) regression, for the analysis of fall outcome counts. Four different count-based regression models (P, NB, zero-inflated Poisson (ZIP), zero-inflated negative binomial (ZINB)) were each individually fitted to four separate fall count datasets from Australia, New Zealand and United States. The finite mixtures of P and NB regression models were also compared to the standard NB model. Both analytical (F, Vuong and bootstrap tests) and graphical approaches were used to select and compare models. Simulation studies assessed the size and power of each model fit. This study confirms that falls count distributions are over-dispersed, but not dispersed due to excess zero counts or heterogeneous population. Accordingly, the P model generally provided the poorest fit to all datasets. The fit improved significantly with NB and both zero-inflated models. The fit was also improved with the NB model, compared to finite mixtures of both P and NB regression models. Although there was little difference in fit between NB and ZINB models, in the interests of parsimony it is recommended that future studies involving modelling of falls count data routinely use the NB models in preference to the P or ZINB or finite mixture distribution. The fact that these conclusions apply across four separate datasets from four different samples of older people participating in studies of different methodology, adds strength to this general guiding principle. © 2009 Elsevier Ltd. All rights reserved

Application of Mice Humanised for Cytochrome P450 CYP2D6 to the Study of Tamoxifen Metabolism and Drug-Drug Interaction with Antidepressants

Tamoxifen is an estrogen receptor antagonist used in the treatment of breast cancer. It is a prodrug that is converted by several cytochrome P450 enzymes to a primary metabolite, N-desmethyltamoxifen (NDT), which is then further modified by CYP2D6 to a pharmacologically potent secondary metabolite, 4-hydroxy-N-desmethyltamoxifen (endoxifen). Antidepressants (ADs), which are often coprescribed to patients receiving tamoxifen, are also metabolized by CYP2D6 and evidence suggests that a drug–drug interaction between these agents adversely affects the outcome of tamoxifen therapy by inhibiting endoxifen formation. We evaluated this potentially important drug–drug interaction in vivo in mice humanized for CYP2D6 (hCYP2D6). The rate of conversion of NDT to endoxifen by hCYP2D6 mouse liver microsomes (MLMs) in vitro was similar to that of the most active members of a panel of 13 individual human liver microsomes. Coincubation with quinidine, a CYP2D6 inhibitor, ablated endoxifen generation by hCYP2D6 MLMs. The NDT-hydroxylation activity of wild-type MLMs was 7.4 times higher than that of hCYP2D6, whereas MLMs from Cyp2d knockout animals were inactive. Hydroxylation of NDT correlated with that of bufuralol, a CYP2D6 probe substrate, in the human liver microsome panel. In vitro, ADs of the selective serotonin reuptake inhibitor class were, by an order of magnitude, more potent inhibitors of NDT hydroxylation by hCYP2D6 MLMs than were compounds of the tricyclic class. At a clinically relevant dose, paroxetine pretreatment inhibited the generation of endoxifen from NDT in hCYP2D6 mice in vivo. These data demonstrate the potential of ADs to affect endoxifen generation and, thereby, the outcome of tamoxifen therapy

Thyroid dysfunction in preterm neonates exposed to iodine

Background: Infants <32 weeks' gestation should not be exposed to topical iodine and its avoidance is recommended during pregnancy and breast feeding. Exposure to contrast media and topical iodine is frequently used in many preterm neonates. Aim: To determine whether thyrotropin levels in preterm infants are affected by exposure to intrapartum/neonatal topical iodine and/or the use of iodinated contrast media. Design: Infants <32 weeks' gestation were recruited. Maternal and neonatal exposures to iodinated contrast media and topical iodine were recorded; levels of thyrotropin and thyroxine were measured from blood-spot cards on postnatal days 7, 14, 28 and the equivalent of 36 weeks' gestation. Results: One hundred and twenty-five infants were exposed to topical iodine/contrast media and 48 infants were unexposed. No infants were treated for hypothyroidism; three infants (exposed group) had transient hyperthyro-tropinaemia. Mean thyrotropin levels were significantly higher on postnatal days 7, 14 and 28 in infants exposed to topical iodine prior to caesarean section compared to unexposed infants, a relationship which persisted after adjustment. Conclusions: In the context of this study, neonatal thyroid dysfunction was seen following exposure to iodine via caesarean section but not via exposure to contrast medi

A protocol for evidence-based targeting and evaluation of statewide strategies for preventing falls among community-dwelling older people in Victoria, Australia

BACKGROUND: Falls are a significant threat to the safety, health and independence of older citizens. Despite the now substantial evidence about effective falls prevention interventions, translation into falls reductions has not yet been fully realised. While the hip fracture rate is decreasing, the number and rate of fall-related hospital admissions among older people is increasing. The challenge now is to deliver the most effective interventions efficiently at a population level, and for these interventions to be taken up by older people. OBJECTIVE: To support the development, and evaluation of, effective falls prevention policy and practice in the state of Victoria, Australia. METHODS: The RE-AIM model (Reach, Efficacy, Adoption, Implementation, Maintenance) was used to identify strategies for an effective programme. Research objectives were developed to support the strategies. These include: (1) identification of subgroups of older people most frequently admitted to hospital for falls; (2) examining the acceptability of established falls interventions; (3) identification of factors that encourage and support relevant lifestyle changes; (4) identifying opportunities to incorporate confirmed interventions in existing programmes and services; (5) developing guidelines for sustainability. The research results will subsequently guide strategy details for the falls prevention plan. RE-AIM will provide the framework for the evaluation structure. OUTCOME MEASURES MEASURES: to monitor the implementation of the selected interventions will be determined for each intervention, based on the five key factors of the RE-AIM model. The overall effect of the falls prevention plan will be monitored by time series analysis of fall-related hospital admission rates for community-dwelling older people

Binding of Hyaluronan to the Native Lymphatic Vessel Endothelial Receptor LYVE-1 Is Critically Dependent on Receptor Clustering and Hyaluronan Organization

The lymphatic endothelial receptor LYVE-1 has been implicated in both uptake of hyaluronan (HA) from tissue matrix and in facilitating transit of leukocytes and tumor cells through lymphatic vessels based largely on in vitro studies with recombinant receptor in transfected fibroblasts. Curiously, however, LYVE-1 in lymphatic endothelium displays little if any binding to HA in vitro, and this has led to the conclusion that the native receptor is functionally silenced, a feature that is difficult to reconcile with its proposed in vivo functions. Nonetheless, as we reported recently, LYVE-1 can function as a receptor for HA-encapsulated Group A streptococci and mediate lymphatic dissemination in mice. Here we resolve these paradoxical findings and show that the capacity of LYVE-1 to bind HA is strictly dependent on avidity, demanding appropriate receptor self-association and/or HA multimerization. In particular, we demonstrate the prerequisite of a critical LYVE-1 threshold density and show that HA binding may be elicited in lymphatic endothelium by surface clustering with divalent LYVE-1 mAbs. In addition, we show that cross-linking of biotinylated HA in streptavidin multimers or supramolecular complexes with the inflammation-induced protein TSG-6 enables binding even in the absence of LYVE-1 cross-linking. Finally, we show that endogenous HA on the surface of macrophages can engage LYVE-1, facilitating their adhesion and transit across lymphatic endothelium. These results reveal LYVE-1 as a low affinity receptor tuned to discriminate between different HA configurations through avidity and establish a new mechanistic basis for the functions ascribed to LYVE-1 in matrix HA binding and leukocyte trafficking in vivo

Building a children's health and environment research agenda in Alberta, Canada: A multi-stakeholder engagement process

As new environmental exposures are continuously identified, environmental influences on health are of growing concern. Knowledge regarding the impacts of environmental exposures is constantly evolving and is often incomplete. In this paper, we describe a multi-phased, multi-stakeholder engagement initiative involving diverse stakeholders with an interest in building a children's environmental health research agenda which would link with and support local practices and policies. The intent of this initiative was to identify priority research issues, themes and questions by implementing a tested Research Planning Model that encompassed the engagement of diverse stakeholders. Here, we describe the model application, which was specifically focused on children's health and the environment. A key component of the model was the ongoing stakeholder engagement process. This included two stakeholder forums, during which participants identified three main research themes (social determinants of health, environmental exposures and knowledge translation) and a short list of research questions. Other key components of the model included the development of a Global Sounding Board of key stakeholders, an Advisory Board and a Scientific Panel with mandates to review and prioritise the research questions. In our case, the Advisory Board and Scientific Panel prioritised questions that focused on environmental exposures related to children's respiratory outcomes. The stakeholder engagement described here is an evolving process with frequent changes of context, sustained by the commitment and dedication of the Children's Environment and Health Research planning team and the Advisory Board. In this article, we share the engagement process, outcomes, successes, challenges and lessons learned from this ongoing experience. Keywordsstakeholder engagement, children's health, environmental health, health researc

Accuracy of evidence-based criteria for identifying an incident hip fracture in the absence of the date of injury: a retrospective database study

Objectives: Hospital discharge data (HDD) in many health systems do not capture the date of injury (DOI); the absence of this date hinders researchers’ ability to distinguish repeat from incident injury admissions. Various approaches using somewhat arbitrary criteria have been explored to increase the accuracy of incident injury identification. However, these approaches have not been validated against a data source which contains DOI. The aim of this study was to determine the accuracy of evidence-based criteria for identifying fall-related incident hip fractures in the absence of DOI using HDD containing DOI as the reference standard. Design: Retrospective database study. Setting: New Zealand. Participants: 8761 patients aged 65+ years admitted for fall-related hip fracture between 1 July 2005 and 30 June 2008, inclusive. Outcome measures: We defined person-identifying HDD containing DOI as the reference standard and calculated measures of the accuracy of evidence-based criteria for identifying fall-related incident hip fractures from HDD not containing DOI. The criteria were principal diagnosis of hip fracture, mechanism of injury indicating a fall, admission type emergency, admission source other than a transfer and presence of hip operation code(s). For a subsequent fall-related hip fracture, additional criteria were time between successive hip fractures ≥120 days, and all external cause-of-injury codes being different to those for the previous hip fracture. Results: The sensitivity and specificity of the criteria for identifying fall-related incident hip fractures from data not containing DOI were 96.7% and 99.3%, respectively, compared with the reference standard. The application of these criteria resulted in a slight underestimation of the percentage of patients with multiple hip fractures. Conclusions: Although it is preferable to have DOI; this study demonstrates that evidence-based criteria can be used to reliably identify fall-related incident hip fractures from the person-identifying HDD when DOI is unavailable