Multimodal imaging of the distal interphalangeal-joint synovio-entheseal complex in psoriatic arthritis (MIDAS): a cross-sectional study on the diagnostic accuracy of different imaging modalities comparing psoriatic arthritis to psoriasis and osteoarthritis.

OBJECTIVE: Can ultrasound (US), MRI and X-ray applied to the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC) discriminate between patients with psoriatic arthritis (PsA), skin psoriasis (PsO) and hand osteoarthritis (OA)? METHODS: In this prospective, cross-sectional study, patients with DIP-joint PsA and nail involvement (n=50), PsO with nail involvement (n=12); and OA (n=13); were consecutively recruited. Risk ratios (RR) were calculated for US, MRI and X-ray findings of the DIP-joint and SEC between diagnoses. RESULTS: New bone formation (NBF) in US and MRI was a hallmark of OA, reducing the risk of having PsA (RR 0.52 (95% CI 0.43 to 0.63) and 0.64 (95% CI 0.56 to 0.74). The OA group was different from PsA and PsO on all MRI and X-ray outcomes reflected in a lower RR of having PsA; RR ranging from 0.20 (95% CI 0.13 to 0.31) for MRI bone marrow oedema (BMO) to 0.85 (95% CI 0.80 to 0.90) in X-ray enthesitis. No outcome in US, MRI or X-ray was significantly associated with a higher risk of PsA versus PsO, although there was a trend to a higher degree of US erosions and NBF in PsA. 82% of PsA and 67% of PsO was treated with disease modifying antirheumatic drugs which commonly reflects the clinical setting. CONCLUSION: High grade of US, MRI and X-ray NBF reduce the RR of having PsA compared with OA. In PsA versus PsO patients, there was a trend for US to demonstrate more structural changes in PsA although this did not reach significance.

Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial.

OBJECTIVE: To compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA). METHODS: In this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)-100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients' global assessment of disease impact. RESULTS: 206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI -0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups. CONCLUSION: In individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks. TRIAL REGISTRATION NUMBER: NCT03843931.

Change in psoriatic arthritis outcome measures impacts SF-36 physical and mental component scores differently: an observational cohort study.

OBJECTIVE: The objective was to investigate interplay and physical and mental component scores between change (Δ) in health-related quality of life (HRQoL) quantified by the physical component score (PCS) and mental component score (MCS) retrieved from short-form health survey (SF-36), change in disease activity (ΔDAS28CRP) and manifestations of PsA. METHODS: PsA patients initiating new medical therapy were enrolled. Independent disease measures evaluating disease activity, enthesitis, psoriasis, pain and fatigue were collected at treatment initiation and after 4 months. Interplay between independent disease measures and dependent outcome measures, ΔPCS and ΔMCS, was described with univariate regression analyses. Multivariate regression analyses were applied to assess the impact of independent variables, such as individual disease outcome measures vs ΔDAS28CRP on ΔPCS and ΔMCS. RESULTS: One hundred and eight PsA patients were included. In the univariate regression analyses, improvement in fatigue, pain and disability were associated with improvement in ΔPCS (ß; -2.08, -0.18 and -13.00, respectively; all P < 0.001) and ΔMCS (ß; -1.59, -0.12 and -6.07, respectively; P < 0.001, P < 0.001 and P = 0.003, respectively). When patient-reported outcomes were included in the final multivariate models, improvements in ΔPCS and ΔMCS were associated with improvements in pain, fatigue and disability (P < 0.001). Improvement in enthesitis impacted ΔPCS positively (ß -0.31, P < 0.001). No association was found between change in skin psoriasis, ΔPCS and ΔMCS (ß 0.15, P = 0.056 and ß 0.05, P = 0.561, respectively). CONCLUSION: In this PsA patient cohort, diminishing pain, disability and fatigue improved PCS and MCS significantly. Changes in enthesitis and psoriasis did not grossly impact HRQoL compared with DAS28CRP. Individual PsA manifestations influence HRQoL differently, which is important clinically when targeting treatment. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02572700.

Novel application of optical coherence tomography and capillaroscopy in psoriatic arthritis in relationship to psoriasis and hand osteoarthritis.

OBJECTIVES: Nailfold video capillaroscopy (NVC) and angiographic optical coherence tomography (OCTA) have potential in diagnosing PsA and differentiating it from psoriasis vulgaris (PsO) and hand OA. We aimed to assess the diagnostic properties of NVC and OCTA in patients with PsA compared with patients with PsO and hand OA based on nailfold capillary patterns. METHODS: Patients with DIP joint PsA and nail involvement (n = 50), PsO with nail involvement (n = 12) and OA (n = 13) were included in this cross-sectional study. Capillaries were evaluated semi-quantitatively and qualitatively. Differences in capillary findings between groups were assessed using mixed linear models. Binary logistic regression analyses were performed to determine the probability for PsA diagnosis based on capillaroscopy findings. RESULTS: Below mean capillary density and reduced nailfold blood flow in OCTA images distinguished PsA from both PsO (P = 0.004 and P = 0.052, respectively) and OA (P = 0.024 and P < 0.001, respectively). Qualitative analysis revealed that glomerular capillaries were found in only 3% of PsA patients but in 13% of PsO patients (P = 0.003). Furthermore, crossed vessels were seen in only 55% of PsA patients and 71% of PsO patients (P = 0.043). NVC microhaemorrhage was dominant in PsA patients (13%) and significantly different from OA patients (P <0.05). No capillary pattern was associated with an increased probability of the PsA diagnosis. CONCLUSION: A pathognomonic pattern for PsA diagnosis was not identified; however, we demonstrated some characteristic capillaroscopy findings for PsA, such as decreased capillary density, reduced blood flow and fewer crossed vessels in OCTA and presence of NVC microhaemorrhages.

Predicting Hospital Resource Use During COVID-19 Surges: A Simple but Flexible Discretely Integrated Condition Event Simulation of Individual Patient-Hospital Trajectories.

OBJECTIVES: To assist with planning hospital resources, including critical care (CC) beds, for managing patients with COVID-19. METHODS: An individual simulation was implemented in Microsoft Excel using a discretely integrated condition event simulation. Expected daily cases presented to the emergency department were modeled in terms of transitions to and from ward and CC and to discharge or death. The duration of stay in each location was selected from trajectory-specific distributions. Daily ward and CC bed occupancy and the number of discharges according to care needs were forecast for the period of interest. Face validity was ascertained by local experts and, for the case study, by comparing forecasts with actual data. RESULTS: To illustrate the use of the model, a case study was developed for Guy's and St Thomas' Trust. They provided inputs for January 2020 to early April 2020, and local observed case numbers were fit to provide estimates of emergency department arrivals. A peak demand of 467 ward and 135 CC beds was forecast, with diminishing numbers through July. The model tended to predict higher occupancy in Level 1 than what was eventually observed, but the timing of peaks was quite close, especially for CC, where the model predicted at least 120 beds would be occupied from April 9, 2020, to April 17, 2020, compared with April 7, 2020, to April 19, 2020, in reality. The care needs on discharge varied greatly from day to day. CONCLUSIONS: The DICE simulation of hospital trajectories of patients with COVID-19 provides forecasts of resources needed with only a few local inputs. This should help planners understand their expected resource needs.

Exercise therapy and patient education versus intra-articular saline injections in the treatment of knee osteoarthritis: an evidence-based protocol for an open-label randomised controlled trial (the DISCO trial).

BACKGROUND: Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the 'active' ingredients are unknown. Designing and executing an adequate and 'blindable placebo' version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used 'state-of-art' exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA. METHODS: In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients' global assessment of disease impact, physical performance tests, and presence of knee joint swelling. DISCUSSION: This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019.

Comorbidities, pain and fatigue in psoriatic arthritis, psoriasis and healthy controls: a clinical cohort study.

OBJECTIVES: To explore the prognostic value of pre-specified comorbidities on treatment outcomes in PsA, and to compare baseline data with cutaneous psoriasis without arthritis and healthy controls (HC). METHODS: Patients initiating conventional synthetic/biological disease-modifying antirheumatic drugs were enrolled in this clinical observational cohort study, and data on comorbidities, and clinical and patient-reported outcomes were retrieved at baseline and after 4 months. Pearson's chi-squared tests were performed to investigate the prognostic value of pre-specified comorbidities and achievement of ACR20, DAPSA50 and MDA. Mann-Whitney U tests were used to compare OMERACT PsA Core Outcome Set (COS) measures at baseline and follow-up for the pre-specified comorbidities. RESULTS: A total of 100 PsA patients were included at baseline. Statistically significantly fewer patients with obesity achieved DAPSA50 compared with patients without obesity (P =0.035), and fewer patients with hypertension (P =0.034) and Charlson Comorbidity Index (CCI) ≥1 (P =0.027), respectively, achieved MDA compared with patients without these comorbidities. Patients with obesity, hypertension, widespread pain, and CCI ≥1 had significantly worse COS measures at follow-up compared with patients without these comorbidities. At baseline, patients with PsA had higher disease burden compared with patients with cutaneous psoriasis and HC, including higher pain (P <0.001) and fatigue (P <0.001) scores, and more widespread pain (P =0.002). CONCLUSION: Obesity, hypertension and CCI ≥1 were prognostic factors for poorer treatment outcome rates in PsA. Pain and fatigue were more frequently reported among patients with PsA compared with patients with cutaneous psoriasis and HC. TRIAL REGISTRATION: The Danish National Committee on Health Research Ethics: H-15009080; Data Protection Agency: 2012-58-0004; ClinicalTrials.gov: NCT02572700.

Efficiency Model of Cladribine Tablets Versus Infusion-Based Disease-Modifying Drugs for Patients with Relapsing-Remitting Multiple Sclerosis.

INTRODUCTION: To develop a simulation model assessing the efficiency of using cladribine tablets versus infusion-based disease-modifying drugs (DMDs) for the treatment of relapsing-remitting multiple sclerosis (RRMS) from a facility perspective in the UK. METHODS: A scheduling algorithm was developed to simulate day-case admissions and calculate the mean changes to resource use and time burden for patients in a facility that transitions from infusion-based treatments to cladribine tablets over 1 year. Model inputs and assumptions were based on previous research and expert opinion. Model validation and quality checks were performed and additional scenario analyses were also conducted. RESULTS: The model successfully scheduled all infusion treatments in the base case and no patients were left off the schedule as a result of lack of capacity. Modeled base-case outcomes increased in future scenarios owing to a 35% increase in demand. The introduction of cladribine tablets reduced these impacts. Specifically, the difference in mean daily utilization was reduced in the future scenario from 13% to 3% as 8% of patients moved to cladribine tablets; annual administration costs decreased by 96% and annual time burden decreased by 90%. Results from additional scenarios showed the largest benefits from switching current infusion patients to cladribine tablets were realized in facilities having moderate to high resource utilization. CONCLUSIONS: This model provides facility decision-makers the ability to assess the efficiency of using cladribine tablets rather than an infusion-based DMD. The simulation quantified the benefits gained from reducing the burden on facility resources by switching some patients with RRMS from infusion-based DMDs to cladribine tablets. Overall, modeled outcomes increased in future scenarios owing to an increase in demand, although the introduction of cladribine tablets reduced this impact.

Relationship Between Fatigue and Inflammation, Disease Duration, and Chronic Pain in Psoriatic Arthritis: An Observational DANBIO Registry Study.

OBJECTIVE: Fatigue is one of the most significant symptoms, and an outcome of great importance, in patients with psoriatic arthritis (PsA), but associations between underlying components of fatigue experienced by patients in relation to the disease have been sparsely investigated. The objectives were to describe the degree of fatigue in patients with PsA, and to examine important components associated with fatigue. METHODS: We performed a cross-sectional survey including patients registered in the Danish nationwide registry DANBIO from December 2013 to June 2014. Principal component analysis (PCA) was used to identify factors associated with fatigue. RESULTS: A total of 1062 patients with PsA were included in the study. A PCA reduced co-variables into 3 components explaining 63% of fatigue in patients. The first component, contributing to 31% of fatigue, was composed of inflammatory factors including swollen and tender joints, physician's global assessment, elevated C-reactive protein (CRP), and high Pain Detect Questionnaire (PDQ) score. The second component, contributing to 17% of fatigue, consisted of increasing age and long disease duration. The third component, contributing to 15% of fatigue, consisted of high PDQ score, tender joint count, increasing age, and concomitant low CRP, suggestive of a chronic pain component consisting of central pain sensitization or structural joint damage. CONCLUSION: Fatigue in patients with PsA may be driven by clinical inflammatory factors, disease duration, and chronic pain in the absence of inflammation.

Cooking Up a Transparent Model Following a DICE Recipe.

When a model is built, it tends to be an iterative process. The ideal model building process starts with constructing a top-level model (that works) and then digging deeper into the sections that need more details. A good model tends to have a long life and be both adapted and updated. A perfectly transparent first model (in whatever platform or programming language it might be) therefore tends to get increasingly convoluted. Yet, it still needs to be submitted and reviewed since it will likely be used as support to facilitate possibly multi-million Euro decisions. So, any modelling method should be able to accept substantial changes and updates of the model without compromising (any hopefully existing) transparency. One method that is gaining traction has its heritage in one of the oldest types of structured algorithms we have-the cooking recipe. Regardless of whether you are looking at a recipe for Swedish meatballs or a recipe to prepare the poisonous Fugu fish, the structure of the recipe is the same. It begins with a list of ingredients with the cooking steps to follow. Combining the 'recipe' idea with a common software like Excel® (which tends to be available on most computers), and the need to 'cook' all kinds of different model types (Markov, micro-simulation, discrete-event simulation, partitioned survival), leads to the DICE method (Caro in Pharmacoeconomics 34(7):655-672, 2016). It starts by listing the initial take on the ingredients needed for the model (in DICE called 'conditions'). Just like writing a recipe, it is easy to add ingredients to this list later as needed. Then the actual 'cooking' is specified as a list of the events needed to fully represent the disease and interventions that will take place, followed by the instructions for each event. Using this approach, it becomes as easy to look at different models as it is to look at different recipes. The simplicity, flexibility and standardized structure, but especially its transparency, are the main features of DICE.

Incidence and time trends of joint surgery in patients with psoriatic arthritis: a register-based time series and cohort study from Denmark.

OBJECTIVE: To investigate time-trends and cumulative incidence of joint surgery among patients with psoriatic arthritis (PsA) compared with the general population. METHODS: In this nationwide register-based cohort study, The Danish National Patient Registry was used to identify incident PsA patients. The 5-year incidence rates (IR) and incidence rate ratios (IRR) of joint surgery were calculated in four calendar-period defined cohorts. Each patient was matched with ten non-PsA individuals from the general population cohort (GPC). The cumulative incidences of any joint and joint-sacrificing surgery, respectively, were estimated using the Aalen-Johansen method. RESULTS: From 1996 to 2017, 11 960 PsA patients (mean age 50 years; 57% female) were registered. The IRR of any joint surgery was twice as high for PsA patients compared with GPCs across all calendar periods. Among patients with PsA, 2, 10 and 29% required joint surgery at 5, 10 and 15 years after diagnosis. The risk of surgery in PsA patients diagnosed at 18-40 years was higher (22%) than in GPC 60+ year old (20%) after 15 years of follow-up. CONCLUSIONS: The use of joint surgery among PsA patients remained around twofold higher from 1996 to 2012 compared with GPC. After 15 years of follow-up, nearly 30% of the PsA patients had received any surgery, and even a person diagnosed with PsA at the age of 18-40 years had a higher risk of surgery than GPCs of 60+ year old. Thus, the high surgical rates represent an unmet need in the current treatment of PsA.

Ultrasound pathology of the entheses in an age and gender stratified sample of healthy adult subjects: a prospective cross-sectional frequency study.

OBJECTIVES: Ultrasound (US) examination of the entheses is increasingly used. However, little is known about US findings in the entheses in asymptomatic persons. The aim of this study was to investigate the appearance of US signs in the enthuses of the lower limb in asymptomatic subjects. METHODS: We recruited 64 subjects, eight women and eight men whose ages covered four decades, from 20 to 60 years. None had tendon or joint disease in the lower limbs. Participants were examined by a rheumatologist and blood samples were collected to rule out enthesis pathology. The enthesis of the dominant leg were examined with grey-scale and Doppler US to evaluate increased thickness, changed structure, enthesophytes/calcifications, erosions, and colour Doppler signal. RESULTS: Ultrasound examination of 320 entheses was made. At enthesis level, elementary lesions were seen at 73 (22.8%) sites, at subject-level 47 (73.4%) persons showed elementary lesions, in 27 (57%) only one enthesis was affected. Doppler activity was seen in four sites, three at the quadriceps insertion. Most common US elementary lesion was enthesophytes at the Achilles and quadriceps tendon insertion. A tendency towards more elementary lesions was seen in men, and a slight increase was seen with increasing age, however, not statistically significance. CONCLUSIONS: Our findings suggest that US can be used to diagnose/examine subjects in adulthood for pathological changes in the entheses; however, caution should be taken regarding enthesophytes of the quadriceps and Achilles tendon.

Pain Mechanisms and Ultrasonic Inflammatory Activity as Prognostic Factors in Patients With Psoriatic Arthritis: A Prospective Cohort Study.

OBJECTIVE: To study the prognostic value of widespread pain and of musculoskeletal ultrasound (US) examination for subsequent treatment outcomes in patients with psoriatic arthritis (PsA). METHODS: An exploratory prospective cohort study enrolled patients with PsA initiating biologic or conventional synthetic disease-modifying antirheumatic drugs in routine care. Clinical, US, and patient-reported measures were collected at baseline and after 4 months. Widespread nonarthritic pain (WP) was defined as a Widespread Pain Index score of ≥4 with pain in ≥4 of 5 regions. PsA activity by US was defined as color Doppler (yes/no) in selected entheses, joints, or tendons. The main response criteria included the American College of Rheumatology 20% improvement, the Disease Activity in Psoriatic Arthritis 50% improvement, and minimal disease activity. The primary analyses were age- and sex-adjusted logistic regression. RESULTS: WP was present in 24 of 69 included patients (35%) and was associated with worse patient-reported and composite baseline measures, while US and other objective findings were similar to those in patients without WP. The odds of reaching minimal disease activity after 4 months were significantly greater for patients enrolled without WP (odds ratio 18.43 [95% confidence interval 1.51, 224.41]; P = 0.022), while WP did not impair other response measures. Patients with baseline color Doppler activity (n = 42 [61%]) had a worse objective PsA burden, but their chance of treatment response was comparable to those without color Doppler. CONCLUSION: More than one-third of patients with PsA presented with WP, which was associated with worse patient-reported scores and failure to achieve minimal disease activity following conventional synthetic or biologic disease-modifying antirheumatic drug therapy. PsA activity by color Doppler US had no influence on subsequent treatment response in this PsA cohort.

Trusting the Results of Model-Based Economic Analyses: Is there a Pragmatic Validation Solution?

Models have become a nearly essential component of health technology assessment. This is because the efficacy and safety data available from clinical trials are insufficient to provide the required estimates of impact of new interventions over long periods of time and for other populations and subgroups. Despite more than five decades of use of these decision-analytic models, decision makers are still often presented with poorly validated models and thus trust in their results is impaired. Among the reasons for this vexing situation are the artificial nature of the models, impairing their validation against observable data, the complexity in their formulation and implementation, the lack of data against which to validate the model results, and the challenges of short timelines and insufficient resources. This article addresses this crucial problem of achieving models that produce results that can be trusted and the resulting requirements for validation and transparency, areas where our field is currently deficient. Based on their differing perspectives and experiences, the authors characterize the situation and outline the requirements for improvement and pragmatic solutions to the problem of inadequate validation.

Adding Events to a Markov Model Using DICE Simulation.

BACKGROUND: Health care decisions are often made under uncertainty and modeling is used to inform the choices and possible consequences. State-transition ("Markov") models are commonly used but they represent the problem solely in terms of states; events are not explicitly considered. METHODS: Discretely integrated condition event (DICE) simulation provides for both aspects that persist over time ("conditions") and for those happening at a point in time ("events"). A Markov model can be specified in DICE by representing states as conditions with a recurrent transition event processing transition probabilities, and other events added explicitly. RESULTS: The DICE specification of a Markov model is compact because transitions are enumerated only once; it is very transparent, as these specifications are tabulated rather than programmed in code; and flexibility is enhanced by the ease with which alternative structures are specified. Events can be added to represent clinical occurrences, treatment features, health care activities, and any other relevant aspect of this type. They may coincide with the transition event or occur at their own times. Varying cycle times and structural sensitivity analyses are easy to implement. LIMITATIONS: Execution of a DICE simulation using a macro in spreadsheet software can be slow, especially for complex models requiring stochastic analyses replicated thousands of times. Modelers wishing to use other software can still use the tabular specification ideas to expand their Markov models, but the descriptions provided here may not be entirely applicable. Another limitation is the inability of these simulations to handle constrained resources or interactions among patients. CONCLUSIONS: With DICE simulation, it is possible to expand the Markov formulation to include explicitly many events occurring at various times.

Validation of a DICE Simulation Against a Discrete Event Simulation Implemented Entirely in Code.

BACKGROUND: Modeling is an essential tool for health technology assessment, and various techniques for conceptualizing and implementing such models have been described. Recently, a new method has been proposed-the discretely integrated condition event or DICE simulation-that enables frequently employed approaches to be specified using a common, simple structure that can be entirely contained and executed within widely available spreadsheet software. To assess if a DICE simulation provides equivalent results to an existing discrete event simulation, a comparison was undertaken. METHODS: A model of osteoporosis and its management programmed entirely in Visual Basic for Applications and made public by the National Institute for Health and Care Excellence (NICE) Decision Support Unit was downloaded and used to guide construction of its DICE version in Microsoft Excel®. The DICE model was then run using the same inputs and settings, and the results were compared. RESULTS: The DICE version produced results that are nearly identical to the original ones, with differences that would not affect the decision direction of the incremental cost-effectiveness ratios (<1% discrepancy), despite the stochastic nature of the models. LIMITATION: The main limitation of the simple DICE version is its slow execution speed. CONCLUSIONS: DICE simulation did not alter the results and, thus, should provide a valid way to design and implement decision-analytic models without requiring specialized software or custom programming. Additional efforts need to be made to speed up execution.

The Economic Impact of Lower Protein Infant Formula for the Children of Overweight and Obese Mothers.

The global prevalence of obesity is rising rapidly, highlighting the importance of understanding risk factors related to the condition. Childhood obesity, which has itself become increasingly prevalent, is an important predictor of adulthood obesity. Studies suggest that the protein content consumed in infanthood is an important predictor of weight gain in childhood, which may contribute to higher body mass index (BMI). For instance, there is evidence that a lower protein infant formula (lpIF) for infants of overweight or obese mothers can offer advantages over currently-used infant formulas with regard to preventing excessive weight gain. The current study used health economic modelling to predict the long-term clinical and economic outcomes in Mexico associated with lpIF compared to a currently-used formula. A discrete event simulation was constructed to extrapolate the outcomes of trials on the use of formula in infanthood to changes in lifetime BMI, the health outcomes due to the changes in BMI and the healthcare system costs, productivity and quality of life impact associated with these outcomes. The model predicts that individuals who receive lpIF in infancy go on to have lower BMI levels throughout their lives, are less likely to be obese or develop obesity-related disease, live longer, incur fewer health system costs and have improved productivity. Simulation-based economic modelling suggests that the benefits seen in the short term, with the use of lpIF over a currently-used formula, could translate into considerable health and economic benefits in the long term. Modelling over such long timeframes is inevitably subject to uncertainty. Further research should be undertaken to improve the certainty of the model.

Cost-Effectiveness Analysis of Smoking Cessation Interventions in Japan Using a Discrete-Event Simulation.

BACKGROUND: Smoking cessation medications have been shown to yield higher success rates and sustained abstinence than unassisted quit attempts. In Japan, the treatments available include nicotine replacement therapy (NRT) and varenicline; however, unassisted attempts to quit smoking remain common. OBJECTIVE: The objective of this study was to compare the health and economic consequences in Japan of using pharmacotherapy to support smoking cessation with unassisted attempts and the current mix of strategies used. METHODS: A discrete-event simulation that models lifetime quitting behaviour and includes multiple quit attempts (MQAs) and relapses was adapted for these analyses. The risk of developing smoking-related diseases is estimated based on the duration of abstinence. Data collected from a survey conducted in Japan were used to determine the interventions selected by smokers initiating a quit attempt and the time between MQAs. Direct and indirect costs are assessed (expressed in 2014 Japanese Yen). RESULTS: Using pharmacotherapy (NRT or varenicline) to support quit attempts proved to be dominant when compared with unassisted attempts or the current mix of strategies (most are unassisted). The results of stratified analyses by age imply that smoking cessation improves health outcomes across all generations. Indirect costs due to premature death leading to lost wages are an important component of the total costs, exceeding the direct medical cost estimates. CONCLUSIONS: Increased utilisation of smoking cessation pharmacotherapy to support quit attempts is predicted to lead to an increase in the number of smokers achieving abstinence, and provide improvements in health outcomes over a lifetime with no additional costs.