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

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

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

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

External validation of a colorectal cancer model against screening trial long term follow-up data

Objectives: The ScHARR Bowel Cancer Screening Model has been used to make decisions about screening strategies in England. The objective of this study was to perform external validation of the ScHARR model against long-term follow-up data about colorectal cancer (CRC) incidence and mortality reductions due to screening, from the Nottingham Trial of guaiac Faecal Occult Blood Testing for CRC, and the UK Flexible Sigmoidoscopy Screening Trial. Methods: The ScHARR model was adapted prior to validation to reflect the setting of each trial in terms of population characteristics, details of screening and surveillance programmes, uptake of screening and further investigations and study follow-up. The impact of using current versus historical CRC incidence and mortality data in the validation was also examined by carrying out a series of analyses in which historical data from different years was included in the model. Results: The ScHARR model was able to predict CRC incidence and mortality rate/hazard ratios from both trials to well within the 95% confidence intervals in the observed data. Whilst it was less accurate in predicting absolute incidence and mortality rates, modelling historical incidence and mortality data enabled these predictions to be improved considerably. Conclusions: The ScHARR model is able to replicate the long-term relative benefit from screening observed in two large-scale UK based screening trials and can therefore be considered to be an appropriate tool to facilitate decision making around the English bowel cancer screening programme

Optimising Bowel Cancer Screening Phase 1: Optimising the cost effectiveness of repeated FIT screening and screening strategies combining bowel scope and FIT screening

ScHARR has been commissioned by the UK National Screening Committee (NSC) to consider the costeffectiveness and endoscopy capacity requirements of a variety of different screening options incorporating faecal immunochemical testing (FIT) and bowel scope (BS) within the Bowel Cancer Screening Programme (BCSP). An existing cost-effectiveness model was used. The model was refined considerably, new data included and model validation was undertaken. All FIT thresholds between 20 and 180 µg/ml were modelled. Analyses were undertaken to determine which screening strategies involving repeated FIT screening and/or bowel scope are most cost-effective given endoscopy constraints. Note that the conclusions reached are based on optimising cost-effectiveness where effectiveness is measured in terms of QALYs gained. If the aim was to optimise QALY gains or CRC incidence/mortality reduction then conclusions would be different. The analysis without endoscopy constraints indicates that the most cost effective screening strategy is the one which delivers the most intensive screening. Regardless of capacity constraints the current screening strategies (gFOBT 2-yearly 60-74 with or without bowel scope age 55) are dominated by a FIT screening strategy (i.e. a FIT strategy exists which is more effective and less expensive). For repeated FIT screening it is recommended that the screening interval is kept to 2-yearly screening. However, increased benefits may be obtained by re-inviting non-attenders after a 1 year interval. The optimal starting age for a repeated FIT screening strategy is 50 or 51 hence it is suggested that the screening start age is reduced compared to what is currently used in the BCSP. The optimal upper screening age varies between 65 and 74, depending on the capacity constraint used. The optimal FIT threshold depends on the available capacity for screening referral colonoscopies. With 50,000 screening referral colonoscopies (current capacity) then we recommend a strategy of 2-yearly, age 51-65, FIT161 (8 screens). With 70,000 screening referral colonoscopies (current capacity) then we recommend a strategy of: 2-yearly, age 50-70, FIT153 (11 screens). If 90,000 screening referral colonoscopies is considered feasible to achieve in the future then we recommend a strategy of 2-yearly, age 50-74, FIT124 (13 screens). In terms of bowel scope screening the model found uncertainty in whether it is cost effective to replace one FIT screen with a one-off bowel scope at age 58/59. However, a repeated FIT screening strategy requiring 125k screening referral colonoscopies annually would be far more effective and cost effective than a one-off bowel scope at age 59. Such strategies could be considered to have equivalent ‘endoscopy capacity’ (assuming that 10 bowel scopes and 4 screening referral colonoscopies are equivalent ).Hence, if bowel scope capacity could be used for undertaking screening referral colonoscopies this would result in higher effectiveness and cost-effectiveness

Sensing RF fields with a distant stand-alone Rydberg-atomic receiver

We combine a rubidium vapour cell with a corner-cube prism reflector to form a passive RF receiver, allowing the detection of microwave signals at a location distant from the active components required for atomic sensing. This compact receiver has no electrical components and is optically linked to the active base station by a pair of free-space laser beams that establish an electromagnetically induced transparency scenario in the atomic vapour. Microwave signals at the receiver location are imprinted onto an optical signal which is detected at the base station. Our stand-alone receiver architecture adds important flexibility to Rydberg-atom based sensing technologies, which are currently subject to significant attention. We demonstrate a ~20 m link with no particular effort and foresee significant future prospects of achieving a much larger separation between receiver and base station