Economics of tandem mass spectrometry screening of neonatal inherited disorders

Objectives: The aim of this study was to evaluate the cost-effectiveness of neonatal screening for phenylketonuria (PKU) and medium-chain acyl-coA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (tandem MS). Methods: A systematic review of clinical efficacy evidence and cost-effectiveness modeling of screening in newborn infants within a UK National Health Service perspective was performed. Marginal costs, life-years gained, and cost-effectiveness acceptability curves are presented. Results: Substituting the use of tandem MS for existing technologies for the screening of PKU increases costs with no increase in health outcomes. However, the addition of screening for MCAD deficiency as part of a neonatal screening program for PKU using tandem MS, with an operational range of 50,000 to 60,000 specimens per system per year, would result in a mean incremental cost of −£17,298 (−£129,174, £66,434) for each cohort of 100,000 neonates screened. This cost saving is associated with a mean incremental gain of 57.3 (28.0, 91.4) life-years. Conclusions: Cost-effectiveness analysis using economic modeling indicates that substituting the use of tandem MS for existing technologies for the screening of PKU alone is not economically justified. However, the addition of screening for MCAD deficiency as part of a neonatal screening program for PKU using tandem MS would be economically attractive

Newborn screening using tandem mass spectrometry: A systematic review

Objectives: To evaluate the evidence for the clinical effectiveness of neonatal screening for phenylketonuria (PKU) and medium-chain acyl-coA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (tandem MS). Study design: Systematic review of published research. Data sources: Studies were identified by searching 12 electronic bibliographic databases; conference proceedings and experts consulted. Results: Six studies were selected for inclusion in the review. The evidence of neonatal screening for PKU and MCAD deficiency using tandem MS was primarily from observational data of large-scale prospective newborn screening programmes and systematic screening studies from Australia, Germany and the USA. Tandem MS based newborn screening of dried blood spots for PKU and/or MCAD deficiency was shown to be highly sensitive (>93.220%) and highly specific (>99.971%). The false positive rate for PKU screening was less than 0.046% and for MCAD deficiency the false positive rate was less than 0.023%. The positive predictive values ranged from 20 to 32% and 19 to 100%, respectively. Conclusions: This review suggests that neonatal screening of dried blood spots using a single analytical technique (tandem MS) is highly sensitive and specific for detecting cases of PKU and MCAD deficiency, and provides a basis for modelling of the clinical benefits and potential costeffectiveness

Deterministic quantum state transfer of atoms in a random magnetic field

We propose a method for transferring atoms to a target quantum state for a multilevel quantum system with sequentially increasing, but otherwise unknown, energy splitting. This is achieved with a feedback algorithm that processes off-resonant optical measurements of state populations during adiabatic rapid passage in real-time. Specifically, we reliably perform the transfer $|F=2,m_F=2\rangle \rightarrow |1,1\rangle \rightarrow |2,1\rangle$ for a sample of ultracold $^{87}$Rb in the presence of a random external magnetic field

Impacts of dieback at Pine Lake, Tasmania

The possibility of a new plant disease in alpine plant communities was identified in 1994, following an investigation of dead and dying plants in the Central Plateau Conservation Area. Seven areas of dieback were identified within the affected catchment and monitored. Symptoms included leaf discolouration, loss of foliage and plant death. No disease of this type has previously been recorded in the Australian alpine environment. Temporal and spatial patterns in disease development along with evidence of lesions on plant roots suggested a soil and water-borne pathogen could be contributing to the dieback. A species of Phytophthora was isolated from plant material collected at the site. Investigations have focussed on whether plants at the limits of their range have been more susceptible to a combination of below-average rainfall, above-average temperatures and the presence of pathogens. Initial rapid development of disease symptoms suggested the potential for local extinction of species, including Tasmanian endemics such as Athrotaxis cupressoides, and significant alteration to community structure through a loss or substantial reduction in the tree and shrub layers. However, longer term monitoring suggests short-term disease events followed by recovery of surviving plants with only localised impacts. Management actions have been concentrated on containment, monitoring impacts and investigation of the cause of the dieback

Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis

OBJECTIVE: To evaluate the cost effectiveness of four disease modifying treatments (interferon betas and glatiramer acetate) for relapsing remitting and secondary progressive multiple sclerosis in the United Kingdom. DESIGN: Modelling cost effectiveness. SETTING: UK NHS. PARTICIPANTS: Patients with relapsing remitting multiple sclerosis and secondary progressive multiple sclerosis. MAIN OUTCOME MEASURES: Cost per quality adjusted life year gained. RESULTS: The base case cost per quality adjusted life year gained by using any of the four treatments ranged from £42 000 ($66 469; 61 630) to £98 000 based on efficacy information in the public domain. Uncertainty analysis suggests that the probability of any of these treatments having a cost effectiveness better than £20 000 at 20 years is below 20%. The key determinants of cost effectiveness were the time horizon, the progression of patients after stopping treatment, differential discount rates, and the price of the treatments. CONCLUSIONS: Cost effectiveness varied markedly between the interventions. Uncertainty around point estimates was substantial. This uncertainty could be reduced by conducting research on the true magnitude of the effect of these drugs, the progression of patients after stopping treatment, the costs of care, and the quality of life of the patients. Price was the key modifiable determinant of the cost effectiveness of these treatments

Choice and judgement in developing models for health technology assessment; a qualitative study

Introduction: The role of models in supporting health policy decisions is reliant on model credibility. Credibility is fundamentally determined by the choices and judgements that people make in the process of developing a model. However, the method of uncovering choices and making judgements in model development is largely unreported and is not addressed by modelling methods guidance. Methods: This qualitative study was part of a project examining errors in health technology assessment models. In-depth interviews with academic and commercial modellers were used to obtain descriptions of the model development process. Data were analysed using framework analysis and interpreted in the context of the methodological literature. Results: The activities involved in developing models were characterised according to the themes; understanding the decision problem, conceptual modelling, model implementation, model checking, and engaging with the decision maker. Finding and using evidence was frequently mentioned across these themes. There was marked variation between practitioners in the extent to which conceptual modelling was recognised as an activity distinct from model implementation. Discussion: Methodological approaches to addressing model credibility described in the wider modelling literature highlight the necessity to disentangle the conceptual modelling and implementation activities. Whilst interviewees talked of judgements and choice making throughout model development, discussion indicated that these were based upon skills and experience with no discussion of formal approaches. Methods are required that provide for a systematic approach to uncovering choices, to generating a shared view of consensus and divergence, and for making judgements and choices in model development

The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

PURPOSE: The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model. MATERIALS AND METHODS: An area of approximately 3 cm2 was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of 14C-GD (300 µg kg-1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2 g application of WoundStat™ 30 s after GD challenge. The decontamination efficacy of WoundStat™ against GD was measured by the direct quantification of the distribution of 14C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements. RESULTS: WoundStat™ sequestered approximately 70% of the applied 14C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15 min post WoundStat™ treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat™ treated animals survived the study duration. CONCLUSIONS: The current study has shown that the use of WoundStat™ as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat™ in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.Peer reviewedFinal Accepted Versio

Evaluation of absorbent materials for use as ad hoc dry decontaminants during mass casualty incidents as part of the UK's Initial Operational Response (IOR)

The UK's Initial Operational Response (IOR) is a revised process for the medical management of mass casualties potentially contaminated with hazardous materials. A critical element of the IOR is the introduction of immediate, on-scene disrobing and decontamination of casualties to limit the adverse health effects of exposure. Ad hoc cleansing of the skin with dry absorbent materials has previously been identified as a potential means of facilitating emergency decontamination. The purpose of this study was to evaluate the in vitro oil and water absorbency of a range of materials commonly found in the domestic and clinical environments and to determine the effectiveness of a small, but representative selection of such materials in skin decontamination, using an established ex vivo model. Five contaminants were used in the study: methyl salicylate, parathion, diethyl malonate, phorate and potassium cyanide. In vitro measurements of water and oil absorbency did not correlate with ex vivo measurements of skin decontamination. When measured ex vivo, dry decontamination was consistently more effective than a standard wet decontamination method (“rinse-wipe-rinse”) for removing liquid contaminants. However, dry decontamination was ineffective against particulate contamination. Collectively, these data confirm that absorbent materials such as wound dressings and tissue paper provide an effective, generic capability for emergency removal of liquid contaminants from the skin surface, but that wet decontamination should be used for non-liquid contaminants