Genomic Surveillance of Methicillin-resistant Staphylococcus aureus: A Mathematical Early Modeling Study of Cost-effectiveness.

BACKGROUND: Genomic surveillance of methicillin-resistant Staphylococcus aureus (MRSA) identifies unsuspected transmission events and outbreaks. Used proactively, this could direct early and highly targeted infection control interventions to prevent ongoing spread. Here, we evaluated the cost-effectiveness of this intervention in a model that compared whole-genome sequencing plus current practice versus current practice alone. METHODS: A UK cost-effectiveness study was conducted using an early model built from the perspective of the National Health Service and personal social services. The effectiveness of sequencing was based on the relative reduction in total MRSA acquisitions in a cohort of hospitalized patients in the year following their index admissions. A sensitivity analysis was used to illustrate and assess the level of confidence associated with the conclusions of our economic evaluation. RESULTS: A cohort of 65 000 patients were run through the model. Assuming that sequencing would result in a 90% reduction in MRSA acquisition, 290 new MRSA cases were avoided. This gave an absolute reduction of 28.8% and avoidance of 2 MRSA-related deaths. Base case results indicated that the use of routine, proactive MRSA sequencing would be associated with estimated cost savings of over £728 290 per annual hospitalized cohort. The impact in total quality-adjusted life years (QALYs) was relatively modest, with sequencing leading to an additional 14.28 QALYs gained. Results were most sensitive to changes in the probability of a MRSA-negative patient acquiring MRSA during their hospital admission. CONCLUSIONS: We showed that proactive genomic surveillance of MRSA is likely to be cost-effective. Further evaluation is required in the context of a prospective study.

An economic evaluation of vagus nerve stimulation as an adjunctive treatment to anti-seizure medications for the treatment of drug resistant epilepsy in the United States.

INTRODUCTION: People with recurrent epileptic seizures are typically treated with anti-seizure medications (ASMs). Around a third of epilepsy patients fail to achieve an adequate response to ASMs and may be eligible to receive vagus nerve stimulation (VNS) therapy for their drug-resistant epilepsy (DRE) if they are unsuited to surgery. VNS received approval from the United States (US) Food and Drug Administration agency. However, there has to date been no comprehensive cost effectiveness evaluation of VNS within the US setting. This study was designed, using a US Medicare perspective, to estimate costs and quality-adjusted life years (QALYs) associated with VNS as an adjunct to ongoing ASM therapy, compared to ASMs alone. METHODS: We developed a cohort state transition model in Microsoft Excel, with four health states defined by different percentage reductions in seizure frequency, with a 3-month cycle and transition probabilities derived from published clinical trials and registry data. Sensitivity analyses were conducted to understand the impact of parameter uncertainty. Costs included the VNS device, placement, programming, battery changes, and removal; ASM therapy; adverse events associated with VNS (dyspnea, hoarseness, and cough); and costs associated with seizure burden (i.e. hospitalizations, emergency department visits, neurologist visits). RESULTS: Under base case assumptions, treatment with VNS was associated with a 0.385 QALY gain and a $109,678 saving per patient, when compared with ASM therapy alone. The incremental net monetary benefit (iNMB) was $128,903 at a threshold of $50,000 per QALY, with the positive iNMB indicating that VNS is a highly cost effective treatment. This result is explained by the modeled reduction in relative seizure frequency and associated reduction in healthcare resource use that the VNS group experienced. Sensitivity analyses supported this conclusion. CONCLUSIONS: VNS was evaluated as a cost effective addition to the current standard of care in the treatment of DRE in the US Medicare context.

Anti-seizure medications (ASMs) are drugs commonly prescribed to people with epilepsy to help prevent seizures from reoccurring. But these drugs do not work for all people: around a third keep having seizures despite taking the medication­a condition called drug-resistant epilepsy (DRE). For such people, their main options involve trying different combinations of ASMs, having brain surgery, or having a medical device implanted. In the United States (US), vagus nerve stimulation (VNS) therapy is approved by the Food and Drug Administration agency for DRE patients who are still having focal onset seizures despite trying ASM therapy. Using methods defined by the US evaluation body, the Institute for Clinical and Economic Review, we made an economic model to assess how cost effective VNS would be as an add-on to ASM therapy. The evaluation utilizes a previously published model, which was updated to use costs, health-related quality of life, and mortality estimates relevant to the US Medicare setting. The analysis demonstrated that VNS could generate cost savings when used as an add-on ASM treatment in the US Medicare setting. VNS may reduce the number of seizures, and subsequently improve patient quality of life and result in substantially lower costs for Medicare (e.g. in emergency and hospital care for a person having a seizure). We tested uncertainties in our model using standard methods­these additional analyses allow us to conclude that VNS is highly likely to be a cost effective addition to the current standard of care for DRE treatment from a US perspective.

Conceptualising global health: theoretical issues and their relevance for teaching.

BACKGROUND: There has long been debate around the definition of the field of education, research and practice known as global health. In this article we step back from attempts at definition and instead ask what current definitions tell us about the evolution of the field, identifying gaps and points of debate and using these to inform discussions of how global health might be taught. DISCUSSION: What we now know as global health has its roots in the late 19(th) century, in the largely colonial, biomedical pursuit of 'international health'. The twentieth century saw a change in emphasis of the field towards a much broader conceptualisation of global health, encompassing broader social determinants of health and a truly global focus. The disciplinary focus has broadened greatly to include economics, anthropology and political science, among others. There have been a number of attempts to define the new field of global health. We suggest there are three central areas of contention: what the object of knowledge of global health is, the types of knowledge to be used and around the purpose of knowledge in the field of global health. We draw a number of conclusions from this discussion. First, that definitions should pay attention to differences as well as commonalities in different parts of the world, and that the definitions of global health themselves depend to some extent on the position of the definer. Second, global health's core strength lies in its interdisciplinary character, in particular the incorporation of approaches from outside biomedicine. This approach recognises that political, social and economic factors are central causes of ill health. Last, we argue that definition should avoid inclusion of values. In particular we argue that equity, a key element of many definitions of global health, is a value-laden concept and carries with it significant ideological baggage. As such, its widespread inclusion in the definitions of global health is inappropriate as it suggests that only people sharing these values may be seen as 'doing' global health. Nevertheless, discussion of values should be a key part of global health education. SUMMARY: Our discussions lead us to emphasise the importance of an approach to teaching global health that is flexible, interdisciplinary and acknowledges the different interpretations and values of those practising and teaching the field.

The evolution of global health teaching in undergraduate medical curricula.

BACKGROUND: Since the early 1990s there has been a burgeoning interest in global health teaching in undergraduate medical curricula. In this article we trace the evolution of this teaching and present recommendations for how the discipline might develop in future years. DISCUSSION: Undergraduate global health teaching has seen a marked growth over the past ten years, partly as a response to student demand and partly due to increasing globalization, cross-border movement of pathogens and international migration of health care workers. This teaching has many different strands and types in terms of topic focus, disciplinary background, the point in medical studies in which it is taught and whether it is compulsory or optional. We carried out a survey of medical schools across the world in an effort to analyse their teaching of global health. Results indicate that this teaching is rising in prominence, particularly through global health elective/exchange programmes and increasing teaching of subjects such as globalization and health and international comparison of health systems. Our findings indicate that global health teaching is moving away from its previous focus on tropical medicine towards issues of more global relevance. We suggest that there are three types of doctor who may wish to work in global health - the 'globalised doctor', 'humanitarian doctor' and 'policy doctor' - and that each of these three types will require different teaching in order to meet the required competencies. This teaching needs to be inserted into medical curricula in different ways, notably into core curricula, a special overseas doctor track, optional student selected components, elective programmes, optional intercalated degrees and postgraduate study. SUMMARY: We argue that teaching of global health in undergraduate medical curricula must respond to changing understandings of the term global health. In particular it must be taught from the perspective of more disciplines than just biomedicine, in order to reflect the social, political and economic causes of ill health. In this way global health can provide valuable training for all doctors, whether they choose to remain in their countries of origin or work abroad.

An economic evaluation of vagus nerve stimulation as an adjunctive treatment to anti-seizure medications for the treatment of drug-resistant epilepsy in England.

INTRODUCTION: Anti-seizure medications (ASMs) are commonly used to prevent recurring epileptic seizures, but around a third of people with epilepsy fail to achieve an adequate response. Vagus nerve stimulation (VNS) is clinically recommended for people with drug-resistant epilepsy (DRE) who are not suitable for surgery, but the cost-effectiveness of the intervention has not recently been evaluated. The study objective is to estimate costs and quality-adjusted life-years (QALYs) associated with using VNS as an adjunct to ongoing ASM therapy, compared to the strategy of using only ASMs in the treatment of people with DRE, from an English National Health Service perspective. METHODS: A cohort state transition model was developed in Microsoft Excel to simulate costs and QALYs of the VNS + ASM and ASM only strategies. Patients could transition between five health states, using a 3-month cycle length. Health states were defined by an expected percentage reduction in seizure frequency, derived from randomized control trial data. Costs included the VNS device as well as its installation, setup, and removal; ASM therapy; adverse events associated with VNS (dyspnea, hoarseness, and cough); and health-state costs associated with epilepsy including hospitalizations, emergency department visits, neurologist visits, and primary care visits. A range of sensitivity analyses, including probabilistic sensitivity analysis, were run to assess the impact of parameter and structural uncertainty. RESULTS: In the base case, VNS + ASM had an estimated incremental cost-effectiveness ratio (ICER) of £17,771 per QALY gained compared to ASMs alone. The cost-effective ICER was driven by relative reductions in expected seizure frequency and the differences in health care resource use associated therewith. Sensitivity analyses found that the amount of resource use per epilepsy-related health state was a key driver of the cost component. CONCLUSIONS: VNS is expected to be a cost-effective intervention in the treatment of DRE in the English National Health Service.

PLAIN LANGUAGE SUMMARYPeople with epilepsy are usually given anti-seizure medications (called ASMs) to help prevent their seizures from reoccurring. However, around a third of them will keep having seizures even with the medication; this is called drug-resistant epilepsy (DRE). Treatment options for DRE include, but are not limited to, surgical or therapeutic device-related interventions or trying alternative ASM combinations.In the English National Health Service (NHS), vagus nerve stimulation (VNS) therapy is recommended by the National Institute for Health and Care Excellence (NICE) for DRE patients who are still having seizures despite trying several different ASMs, and who cannot have brain surgery. Following NICE technical standards, we developed an economic model to test whether VNS would be a cost-effective add-on to ASM therapy. The model uses current costs for VNS therapy and takes a more nuanced approach to the longevity of the VNS device than previous research did.Results showed that adding VNS to ASMs can be a cost-effective way to treat DRE in today's NHS in England. VNS reduces the number of seizures, which is expected to improve patients' quality of life and cut NHS costs that would otherwise have been needed to look after patients who had a seizure (for example, emergency visits or inpatient hospital stays). Sensitivity analyses tested aspects of uncertainty in our model. These highlighted the need to further understand the relationship between seizures, their severity, and health care usage if we want to make improved cost-effectiveness analyses about DRE in the future.

Exploratory cost-effectiveness model of electromagnetic navigation bronchoscopy (ENB) compared with CT-guided biopsy (TTNA) for diagnosis of malignant indeterminate peripheral pulmonary nodules.

INTRODUCTION: Lung cancer is accountable for 35 000 deaths annually, and prognosis is improved when the cancer is diagnosed early. CT-guided biopsy (transthoracic needle aspiration, TTNA) and electromagnetic navigation bronchoscopy (ENB) can be used to investigate indeterminate pulmonary nodules if the patient is unfit for surgery. However, there is a paucity of clinical and health economic evidence that directly compares ENB with TTNA in this population group. This cost-effectiveness study aimed to explore potential scenarios whereby ENB may be considered cost-effective when compared with TTNA. METHODS: A cohort decision analytic model was developed using a UK National Health Service perspective. ENB was assumed to have equal sensitivity to TTNA at 82%. Lifetime costs and quality-adjusted life-year (QALY) gain were calculated to estimate the net monetary benefit at a £20 000 per QALY threshold. Sensitivity analyses were used to explore scenarios where ENB could be considered a cost-effective intervention. RESULTS: Under the assumption that ENB has equal efficacy to TTNA, ENB was found to be dominant (less costly and more effective) when compared with TTNA, due to having a reduced risk and cost of adverse events. This conclusion was most sensitive to changes in the cost of intervention, estimates of effectiveness and adverse event rates. DISCUSSION: ENB is expected to be cost-effective when the likelihood of an accurate diagnosis is equal to (or better than) TTNA, which may occur in certain subgroups of patients in whom TTNA is unlikely to accurately diagnose malignancy or when an experienced practitioner achieves a high accuracy with ENB.

A cost-effectiveness analysis of endoscopic eradication therapy for management of dysplasia arising in patients with Barrett's oesophagus in the United Kingdom.

BACKGROUND AND AIMS: Endoscopic eradication therapy (EET) is the first line approach for treating Barrett's oesophagus (BE) related neoplasia globally. The British Society of Gastroenterology (BSG) recommend EET with combined endoscopic resection (ER) for visible dysplasia followed by endoscopic ablation in patients with both low and high grade dysplasia (LGD and HGD). The aim of this study is to perform a cost-effectiveness analysis for EET for treatment of all grades of dysplasia in BE patients. METHODS: A Markov cohort model with a lifetime time horizon was used to undertake a cost-effectiveness analysis. A hypothetical cohort of UK patients diagnosed with BE entered the model. Patients in the treatment arm with LGD and HGD received EET and patients with non-dysplastic BE (NDBE) received endoscopic surveillance only. In the comparator arm, patients with LGD, HGD and NDBE received endoscopic surveillance only. A UK National Health Service (NHS) perspective was adopted and the incremental cost-effectiveness ratio (ICER) was calculated. Sensitivity analysis was conducted on key input parameters. RESULTS: EET for patients with LGD and HGD arising in BE is cost-effective compared to endoscopic surveillance alone (lifetime ICER £3006 per quality adjusted life year [QALY] gained). The results show that, as the time horizon increases, the treatment becomes more cost-effective. The 5 year financial impact to the UK NHS of introducing EET is £7.1m. CONCLUSIONS: EET for patients with low and high grade BE dysplasia, following updated guidelines from the BSG, has been shown to be cost-effective for patients with BE in the UK.