Syed Mohiuddin

Adenosine in myocardial perfusion imaging using positron emission tomography

Because of its unique ability to demonstrate the metabolic consequences of myocardial ischemia, positron emission tomography (PET) is extremely valuable in assessing myocardial viability. PET imaging can identify the myocardial segments that are likely to improve after revascularization and may be more sensitive and specific for the detection of coronary artery disease compared with thallium perfusion imaging. Adenosine has several advantages over dipyridamole as a pharmacologic stress agent for use with PET. It produces maximal vasodilation in a significantly greater percentage of patients, is a more potent coronary vasodilator, and its very short half-life may be ideal for use with the very short half-life radioactive tracers used in PET. When combined with metabolic studies, adenosine may be useful for the assessment of patients who received thrombolytic therapy for an acute myocardial infarction.

Utility values for adults with unipolar depression: Systematic review and meta-analysis

Background. Unipolar depression is a mental illness with a substantial health-related and economic burden. Health interventions for depression predominately focus on improving sufferers’ health-related quality of life (HRQoL). Utility is a measure of HRQoL that is required for use in model-based cost-utility analyses to assess the added value of health interventions. This review aimed to identify, summarize, and where feasible, synthesize published utilities for unipolar depression. Methods. A structured electronic search combining common terms for unipolar depression and utility was conducted in MEDLINE, EMBASE, and PsycINFO. Utility values identified were summarized, and the study designs were appraised in terms of the patient population and valuation method used to generate utilities. Random-effect meta-analyses were applied to pool mean utilities identified for 3 depressive health states (mild, moderate, and severe) elicited from direct and indirect valuation methods separately. Results. Thirty-five studies were identified that reported utilities for various levels of depression severity. The most commonly used direct valuation method for eliciting utilities was standard gamble (SG) (n = 5), and the most commonly used indirect valuation method was EQ-5D (n = 20). The pooled mean (standard deviation) utilities from studies using SG as a direct valuation method were mild = 0.69 (0.14), moderate = 0.52 (0.28), and severe = 0.27 (0.26). The pooled utilities from studies using EQ-5D as an indirect valuation method were mild = 0.56 (0.16), moderate = 0.45 (0.18), and severe = 0.25 (0.15). Conclusions. This systematic review is a useful resource for decision analysts who need health-related utility values to populate model-based cost-utility analyses of health interventions for the management of unipolar depression. Further research is necessary to understand whether direct or indirect valuation methods are the most robust sources for utilities in depression.

Belimumab: a technological advance for systemic lupus erythematosus patients? Report of a systematic review and meta-analysis

Objectives To undertake a systematic review and meta-analysis to investigate clinical effectiveness of belimumab for patients with systemic lupus erythematosus (SLE) and antinuclear and/or anti-double-stranded DNA (dsDNA) autoantibodies. Methods We searched eight electronic databases and reference lists for randomised controlled trials (RCTs) of belimumab against placebo or best supportive care. Quality assessment and random effects meta-analysis were undertaken. Design A meta-analysis of RCTs. Participants 2133 SLE patients. Primary and secondary outcome measures SLE Responder Index (SRI) at week 52. Results Three double-blind placebo-controlled RCTs (L02, BLISS-52 BLISS-76) investigated 2133 SLE patients. BLISS-52 and BLISS-76 trials recruited patients with antinuclear and/or anti-dsDNA autoantibodies and demonstrated belimumab effectiveness for the SRI at week 52. Ethnicity and geographical location of participants varied considerably between BLISS trials. Although tests for statistical heterogeneity were negative, BLISS-52 results were systematically more favourable for all measured outcomes. Meta-analysis of pooled 52-week SRI BLISS results showed benefit for belimumab (OR 1.63, 95% CI 1.27 to 2.09). By week 76, the primary SRI outcome in BLISS-76 was not statistically significant (OR 1.31, 95% CI 0.919 to 1.855).

A Reappraisal of the Risks and Benefits of Treating to Target with Cholesterol Lowering Drugs

Atherosclerotic cardiovascular disease (CVD) is the number one cause of death globally, and lipid modification, particularly lowering of low density lipoprotein cholesterol (LDLc), is one of the cornerstones of prevention and treatment. However, even after lowering of LDLc to conventional goals, a sizeable number of patients continue to suffer cardiovascular events. More aggressive lowering of LDLc and optimization of other lipid parameters like triglycerides (TG) and high density lipoprotein cholesterol (HDLc) have been proposed as two potential strategies to address this residual risk. These strategies entail use of maximal doses of highly potent HMG CoA reductase inhibitors (statins) and combination therapy with other lipid modifying agents. Though statins in general are fairly well tolerated, adverse events like myopathy are dose related. There are further risks with combination therapy. In this article, we review the adverse effects of lipid modifying agents used alone and in combination and weigh these effects against the evidence demonstrating their efficacy in reducing cardiovascular events, cardiovascular mortality, and all cause mortality. For patients with established CVD, statins are the only group of drugs that have shown consistent reductions in hard outcomes. Though more aggressive lipid lowering with high dose potent statins can reduce rates of non fatal events and need for interventions, the incremental mortality benefits remain unclear, and their use is associated with a higher rate of drug related adverse effects. Myopathy and renal events have been a significant concern with the use of high potency statin drugs, in particular simvastatin and rosuvastatin. For patients who have not reached target LDL levels or have residual lipid abnormalities on maximal doses of statins, the addition of other agents has not been shown to improve clinical outcomes and carries an increased risk of adverse events. The clinical benefits of drugs to raise HDLc remain unproven. In patients without known cardiovascular disease, there is conflicting evidence as to the benefits of aggressive pursuit of numerical lipid targets, particularly with respect to all cause mortality. Certainly, in statin intolerant patients, alternative agents with a low side effect profile are desirable. Bile acid sequestrants are an effective and safe choice for decreasing LDLc, and omega-3 fatty acids are safe agents to decrease TG. There remains an obvious need to design and carry out large scale studies to help determine which agents, when combined with statins, have the greatest benefit on cardiovascular disease with the least added risk. These studies should be designed to assess the impact on clinical outcomes rather than surrogate endpoints, and require a comprehensive assessment and reporting of safety outcomes.

Patient flow within UK emergency departments: a systematic review of the use of computer simulation modelling methods

Objectives Overcrowding in the emergency department (ED) is common in the UK as in other countries worldwide. Computer simulation is one approach used for understanding the causes of ED overcrowding and assessing the likely impact of changes to the delivery of emergency care. However, little is known about the usefulness of computer simulation for analysis of ED patient flow. We undertook a systematic review to investigate the different computer simulation methods and their contribution for analysis of patient flow within EDs in the UK. Methods We searched eight bibliographic databases (MEDLINE, EMBASE, COCHRANE, WEB OF SCIENCE, CINAHL, INSPEC, MATHSCINET and ACM DIGITAL LIBRARY) from date of inception until 31 March 2016. Studies were included if they used a computer simulation method to capture patient progression within the ED of an established UK National Health Service hospital. Studies were summarised in terms of simulation method, key assumptions, input and output data, conclusions drawn and implementation of results. Results Twenty-one studies met the inclusion criteria. Of these, 19 used discrete event simulation and 2 used system dynamics models. The purpose of many of these studies (n=16; 76%) centred on service redesign. Seven studies (33%) provided no details about the ED being investigated. Most studies (n=18; 86%) used specific hospital models of ED patient flow. Overall, the reporting of underlying modelling assumptions was poor. Nineteen studies (90%) considered patient waiting or throughput times as the key outcome measure. Twelve studies (57%) reported some involvement of stakeholders in the simulation study. However, only three studies (14%) reported on the implementation of changes supported by the simulation. Conclusions We found that computer simulation can provide a means to pretest changes to ED care delivery before implementation in a safe and efficient manner. However, the evidence base is small and poorly developed. There are some methodological, data, stakeholder, implementation and reporting issues, which must be addressed by future studies.

Combined effect of variable viscosity and thermal conductivity on free convection flow of a viscous fluid in a vertical channel

Purpose – The purpose of this paper is to investigate the effect of exponential viscosity-temperature relation, exponential thermal conductivity-temperature relation and the combined effects of variable viscosity and variable thermal conductivity on steady free convection flow of viscous incompressible fluid in a vertical channel. Design/methodology/approach – The governing equations are solved analytically using regular perturbation method. The analytical solutions are valid for small variations of buoyancy parameter and the solutions are found up to first order for variable viscosity. Since the analytical solutions have a restriction on the values of perturbation parameter and also on the higher order solutions, the authors resort to numerical method which is Runge-Kutta fourth order method. Findings – The skin friction coefficient and the Nusselt number at both the plates are derived, discussed and their numerical values for various values of physical parameters are presented in tables. It is found tha...

Use of value of information in UK health technology assessments

OBJECTIVES The aim of this study was to identify and critically appraise the use of Value of Information (VOI) analyses undertaken as part of health technology assessment (HTA) reports in England and Wales. METHODS A systematic review of National Institute for Health Research (NIHR) funded HTA reports published between 2004 and 2013 identified the use of VOI methods and key analytical details in terms of: (i) types of VOI methodology used; (ii) parameters and key assumptions; and (iii) conclusions drawn in terms of the need for further research. RESULTS A total of 512 HTA reports were published during the relevant timeframe. Of these, 203 reported systematic review and economic modeling studies and 25 of these had used VOI method(s). Over half of the twenty-five studies (n = 13) conducted both EVPI (Expected Value of Perfect Information) and EVPPI (Expected Value of Partial Perfect Information) analyses. Eight studies conducted EVPI analysis, three studies conducted EVPI, EVPPI, and EVSI (Expected Value of Sampling Information) analyses and one study conducted EVSI analysis only. The level of detail reporting the methods used to conduct the VOI analyses varied. CONCLUSIONS This review has shown that the frequency of the use of VOI methods is increasing at a slower pace compared with the published volume of HTA reports. This review also suggests that analysts reporting VOI method(s) in HTA reports should aim to describe the method(s) in sufficient detail to enable and encourage decision-makers guiding research prioritization decisions to use the potentially valuable outputs from quantitative VOI analyses.

A multi-state model to improve the design of an automated system to monitor the activity patterns of patients with bipolar disorder

This paper describes the role of mathematical modelling in the design and evaluation of an automated system of wearable and environmental sensors called PAM (Personalised Ambient Monitoring) to monitor the activity patterns of patients with bipolar disorder (BD). The modelling work was part of an EPSRC-funded project, also involving biomedical engineers and computer scientists, to develop a prototype PAM system. BD is a chronic, disabling mental illness associated with recurrent severe episodes of mania and depression, interspersed with periods of remission. Early detection of the onset of an acute episode is crucial for effective treatment and control. The aim of PAM is to enable patients with BD to self-manage their condition, by identifying the persons normal ‘activity signature’ and thus automatically detecting tiny changes in behaviour patterns which could herald the possible onset of an acute episode. PAM then alerts the patient to take appropriate action in time to prevent further deterioration and possible hospitalisation. A disease state transition model for BD was developed, using data from the clinical literature, and then used stochastically in a Monte Carlo simulation to test a wide range of monitoring scenarios. The minimum best set of sensors suitable to detect the onset of acute episodes (of both mania and depression) is identified, and the performance of the PAM system evaluated for a range of personalised choices of sensors.

Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure

Objective Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction. Methods We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients <75 years; (2) HFpEF patients <75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results. Results In younger patients (<75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (−£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (−£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect. Conclusions We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care.

Economic evaluation of surgical insertion of ventilation tubes for the management of persistent bilateral otitis media with effusion in children

BackgroundThe surgical insertion of Ventilation Tubes (VTs) for the management of persistent bilateral Otitis Media with Effusion (OME) in children remains a contentious issue due to the varying opinions regarding the risks and benefits of this procedure. The aim of this study was to evaluate the economic impact of VTs insertion for the management of persistent bilateral OME in children, providing an additional perspective on the management of one of the commonest medical conditions of childhood.MethodsA decision-tree model was constructed to assess the cost-effectiveness of VTs strategy compared with the Hearing Aids (HAs) alone and HAs plus VTs strategies. The model used data from published sources, and assumed a 2-year time horizon and UK NHS perspective for costs. Outcomes were computed as Quality-Adjusted Life-Years (QALYs) by attaching a utility value to the total potential gains in Hearing Level in decibels (dBHL) over 12 and 24 months. Modelling uncertainty in the specification of decision-tree probabilities and QALYs was performed through Monte Carlo simulation. Expected Value of Perfect Information (EVPI) and partial EVPI (EVPPI) analyses were conducted to estimate the potential value of future research and uncertainty associated with the key parameters.ResultsThe VTs strategy was more effective and less costly when compared with the HAs plus VTs strategy, while the incremental cost-effectiveness ratio for the VTs strategy compared with the HAs strategy was £5,086 per QALY gained. At the willingness-to-pay threshold of £20,000 per QALY, the probability that the VTs strategy is likely to be more cost-effective was 0.58. The EVPI value at population level of around £9.5 million at the willingness-to-pay threshold of £20,000 indicated that future research in this area is potentially worthwhile, while the EVPPI analysis indicated considerable uncertainty surrounding the parameters used for computing the QALYs for which more precise estimates would be most valuable.ConclusionsThe VTs strategy is a cost-effective option when compared with the HAs alone and HAs plus VTs strategies, but the need for additional information from future study is evident to inform this surgical treatment choice. Future studies of surgical and non-surgical treatment of OME in childhood should evaluate the economic impact of pertinent interventions to provide greater context.