Multistate Transition Model Research Articles

99P Cost effectiveness of pembrolizumab in combination with chemotherapy as neoadjuvant therapy and continued as a single agent as adjuvant therapy for high-risk early-stage TNBC in the United States

This analysis evaluated the cost effectiveness of pembrolizumab in combination with chemotherapy as neoadjuvant treatment and continued as a single agent as adjuvant treatment after surgery compared with neoadjuvant chemotherapy for patients with high-risk early-stage triple-negative breast cancer (eTNBC). The analysis was conducted from a US third-party public healthcare payer perspective. A multi-state transition model including four mutually exclusive health states: event-free, locoregional recurrence, distant metastasis, and death was developed to simulate patients’ disease course over lifetime. Efficacy and safety data were derived from the KEYNOTE-522 randomized clinical trial. The model Quality-adjusted life-years (QALYs) were calculated based on EuroQoL-5 Dimensions (EQ-5D) utility data collected in the trial. Costs ($US, in 2021 values) for drug acquisition/administration, adverse events, disease management and subsequent therapies were included. Costs and outcomes were discounted at 3% per year. A series of deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results. In the base-case scenario, pembrolizumab plus chemotherapy followed by pembrolizumab resulted in an expected gain of 3.37 life-years (LYs) and 2.90 QALYs and an incremental cost of $US79,046 compared with chemotherapy alone. The incremental cost per QALY gain was $US27,285/QALY and the incremental cost per LY gain was $US23,489/LY, which were lower than all cost-effectiveness thresholds cited in the literature. Sensitivity analyses showed the results to be robust over plausible values of key model inputs. Compared with neoadjuvant chemotherapy, pembrolizumab in combination with chemotherapy as neoadjuvant treatment and continued as a single agent as adjuvant treatment after surgery is projected to be a cost-effective option for high-risk eTNBC in the US.

Modeling clinical trajectory status of critically ill COVID-19 patients over time: A method for analyzing discrete longitudinal and ordinal outcomes.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

The Impact of Menthol Cigarette Flavor in the U.S.: Cigarette and ENDS Transitions by Sociodemographic Group

A better understanding of how menthol cigarette flavoring and ENDS impact smoking initiation, cessation, and transitions between tobacco products could help elucidate the potential impact of a U.S. menthol ban on combustible tobacco products. A multistate transition model was applied to data on 23,232 adults from Waves 1-4 (2013-2017) of the Population Assessment of Tobacco and Health Study (analysis was conducted in 2020-2021). Transition rates among never, noncurrent, nonmenthol versus menthol cigarette, ENDS, and dual everyday/someday use were estimated, as were transition-specific hazard ratios for age, sex, race/ethnicity, education, and income. Non-Hispanic Blacks who smoked menthol discontinued smoking at a much lower rate than those who smoked nonmenthol (hazard ratio=0.43, 95% CI=0.29, 0.64), but there was no statistically significant difference in the discontinuation rates among non-Hispanic Whites (hazard ratio=0.97, 95% CI=0.80, 1.16) or Hispanics (hazard ratio=0.81, 95% CI=0.56, 1.16). Non-Hispanic Whites who smoked menthol were more likely to become dual users than those who smoked nonmenthol (hazard ratio=1.43, 95% CI=1.14, 1.80). Young adults initiated menthol smoking at a higher rate than older adults (age 18-24 years versus ≥55 years: hazard ratio=2.45, 95% CI=1.44, 4.15) but not nonmenthol smoking (hazard ratio=1.02, 95% CI=0.62, 1.69). There were differences by sex in the impact of menthol flavor on smoking initiation and discontinuation but little difference by education or income. Sociodemographic differences in product transitions should be accounted for when estimating the potential impact of a menthol ban.

Development Dynamics of Health and Social Infrastructure for the Long-term Care - the Case of the Posavje Region.

Background and purposeThe populations of rural areas across Europe, especially Slovenia, are ageing rapidly and the areas themselves are becoming depopulated. Therefore, this study aims to contribute to our understanding of the population dynamics and provide a method for forecasting housing and other long-term care needs.MethodThe surveys questioned those responsible for long-term care, the caretakers in institutional care, and current and potential homecare users in rural areas of Slovenia. We wanted to discover what they considered as crucial in the process of long-term care deinstitutionalization. Our 2020–2050 projections are based on the surveys conducted across 38 municipalities in the Eastern Slovenian region and an in-depth empirical study in Posavje. The results are embedded in the demographic projections and the multistate transition model of the declining functional capacities to forecast the needed housing facilities and human resources.ResultsThe results are the time series of required capacities. Around 60% of respondents in Slovenian rural areas believe that even a better organization of homecare would not allow them to stay at home until death due to inadequately built housing and the absence of a continuous presence of caregivers. These findings were included in the projections. Therefore, community care in the network of Smart Silver Villages was proposed.DiscussionInvestments are needed to renovate the housing stock of older adults and construct sheltered, assisted living housing and specialized households in the community. Moreover, proper education and training of human resources would increase the output. In addition, financial solutions are advised to develop Smart Silver Villages.

How blood pressure predicts frailty transitions in older adults in a population-based cohort study: a multi-state transition model.

BackgroundLow blood pressure (BP) is associated with frailty in older adults. Our aim was to explore how BP predicts transitions between frailty states.MethodsWe used data from the Lausanne cohort Lc65+, a population-based cohort of older adults randomly drawn from a population registry in Switzerland, in 2004, 2009 and 2014. BP was measured using a clinically validated oscillometric automated device and frailty was defined using Fried’s phenotype, every 3 years. We used an illness-death discrete multi-state Markov model to estimate hazard ratios of forward and backward transitions between frailty states (outcome) in relation to BP categories (predictor of interest) with adjustment for sex, age and antihypertensive medication (other predictors).ResultsAmong 4200 participants aged 65–70 years (58% female) at baseline, 70% were non-frail, 27% pre-frail and 2.0% frail. Over an average follow-up of 5.8 years, 2422 transitions were observed, with 1575 (65%) forward and 847 (35%) backward. Compared with systolic BP (SBP) <130 mmHg, the hazard ratio (95% confidence interval) of the transition from non-frail to pre-frail was 0.86 (0.74 to 1.00) for SBP 130–150 mmHg, and 0.89 (0.74 to 1.06) for SBP ≥150 mmHg. Compared with SBP <130 mmHg, the hazard ratio of the transition from pre-frail to frail was 0.71 (0.50 to 1.01) for SBP 130–150 mmHg, and 0.90 (0.62 to 1.32) for SBP ≥150 mmHg. Diastolic BP was a weaker predictor of forward transitions.ConclusionsBP categories had no strong relationship with either forward transitions or backward transitions in frailty states. If our findings are confirmed with greater precision and assuming a causal relationship, they would suggest that there is no well-defined optimal BP level to prevent frailty among older adults.

A multistate transition model for statin-induced myopathy and statin discontinuation.

The overarching goal of this study was to simultaneously model the dynamic relationships among statin exposure, statin discontinuation, and potentially statin‐related myopathic outcomes. We extracted data from the Indiana Network of Patient Care for 134,815 patients who received statin therapy between January 4, 2004, and December 31, 2008. All individuals began statin treatment, some discontinued statin use, and some experienced myopathy and/or rhabdomyolysis while taking the drug or after discontinuation. We developed a militate model to characterize 12 transition probabilities among six different states defined by use or discontinuation of statin and its associated myopathy or rhabdomyolysis. We found that discontinuation of statin therapy was common and frequently early, with 44.4% of patients discontinuing therapy after 1 month, and discontinuation is a strong indicator for statin‐induced myopathy (risk ratio, 10.8; p < 0.05). Women more likely than men (p < 0.05) and patients aged 65 years and older had a higher risk than those aged younger than 65 years to discontinue statin use or experience myopathy. In conclusion, we introduce an innovative multistate model that allows clear depiction of the relationship between statin discontinuation and statin‐induced myopathy. For the first time, we have successfully demonstrated and quantified the relative risk of myopathy between patients who continued and discontinued statin therapy. Age and sex were two strong risk factors for both statin discontinuation and incident myopathy.

Slowing on quantitative EEG is associated with transition to dementia in mild cognitive impairment.

Electroencephalographic (EEG) abnormalities are greater in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) than in MCI due to Alzheimer's disease (MCI-AD) and may anticipate the onset of dementia. We aimed to assess whether quantitative EEG (qEEG) slowing would predict a higher annual hazard of dementia in MCI across these etiologies. MCI patients (n = 92) and healthy comparators (n = 31) provided qEEG recording and underwent longitudinal clinical and cognitive follow-up. Associations between qEEG slowing, measured by increased theta/alpha ratio, and clinical progression from MCI to dementia were estimated with a multistate transition model to account for death as a competing risk, while controlling for age, cognitive function, and etiology classified by an expert consensus panel.Over a mean follow-up of 1.5 years (SD = 0.5), 14 cases of incident dementia and 5 deaths were observed. Increased theta/alpha ratio on qEEG was associated with increased annual hazard of dementia (hazard ratio = 1.84, 95% CI: 1.01-3.35). This extends previous findings that MCI-LB features early functional changes, showing that qEEG slowing may anticipate the onset of dementia in prospectively identified MCI.

An actuarial multi-state transition modelling in long-term care study

With the growing numbers of elderly and numbers of disability among the elderly in the population, long-term care services are at great demand now. Long-term care provides a variety of services by helping the elderly or non-elderly with medical illnesses or disabilities who are unable to foster themselves for prolonged terms. Since Malaysia’s aged care and health care industry still has ways to go in contrast to other countries, such as Australia, therefore, understand the long-term care services could be helpful to provide quality lifestyle for the elderly in the future. We study the multi-state transition model which is the common model used on health-related data. Four levels of core activity restrictions are including in the model to allow the probability of disability to be included in the long-term care cost projection. Estimation of transition intensities are provided by fitting the Australian data with Gompertz and Weibull models. The graphs of actual and fitted transition probabilities are presented for better illustration. We concluded that Gompertz model has the better fit for both male and female in our study. Some limitations and recommendations have been outlined for future studies.

Profiling Delirium Progression in Elderly Patients via Continuous-Time Markov Multi-State Transition Models.

Poor recognition of delirium among hospitalized elderlies is a typical challenge for health care professionals. Considering methodological insufficiency for assessing time-varying diseases, a continuous-time Markov multi-state transition model (CTMMTM) was used to investigate delirium evolution in elderly patients. This is a longitudinal observational study performed in September 2016 in an Italian hospital. Change of delirium states was modeled according to the 4AT score. A Cox model (CM) and a CTMMTM were used for identifying factors affecting delirium onset both with a two-state and three-state model. In this study, 78 patients were enrolled and evaluated for 5 days. Both the CM and the CTMMTM show that urine catheter (UC), aging, drugs, and invasive devices (ID) are risk factors for delirium onset. The CTMMTM model shows that transition from no-delirium/cognitive impairment to delirium was associated with aging (HR = 1.14; 95%CI, 1.05, 1.23) and neuroleptics (HR = 4.3; 1.57, 11.77), dopaminergic drugs (HR = 3.89; 1.2, 12.6), UC (HR = 2.92; 1.09, 7.79) and ID (HR = 1.67; 103, 2.71). These results are confirmed by the multivariable model. Aging, ID, antibiotics, drugs affecting the central nervous system, and absence of moving ability are identified as the significant predictors of delirium. Additionally, it seems that modeling with CTMMTM may show associations that are not directly detectable with the traditional CM.

Determinants of transitions in water and sanitation services in two urban slums of Nairobi: A multi-state modeling approach

Access to improved water, sanitation, and hygiene (WASH) services at the household level remains a good strategy to improve the health and well-being of individuals. Informal settlements, such as urban slums, are at risk of the spread of diseases due to the relative lack of access to safe, clean drinking water and basic sanitation, as well as poor hygiene. Global initiatives, such as the Sustainable Development Goals (SDGs) adopted by the United Nations, are aimed at transitioning households and communities from unimproved to sustained improved states of WASH services. To deepen understanding of the time dynamics between states of WASH services in the Nairobi Urban and Demographic Surveillance System (NUHDSS), this study employs the multi-state transition model to assess the influence of potential risk factors on these transitions. Results indicated that study sites, wealth tertile, age of household head, poverty status, the ethnicity of household head, household ownership, and food security were associated with household transitions of WASH services. There was a lower probability for households to transition from unimproved to improved toilet services than the reverse transition, but a higher chance for households to transition from unimproved to improved water and garbage services. The estimated average time that households spent in the unimproved and improved states before transitioning were, respectively, 35 months and 9 months for toilet services, 7 months and 66 months for water services, and 16 months and 19 months for garbage services. Thus, households tend to remain longer in the unimproved state of toilet and garbage services, and when in the improved states, they transition back relatively faster compared to water services. In conclusion, sanitation services in Nairobi informal settings remain largely unsatisfactory as transitions to improved services are not sustained. It is therefore important for governments, policy-makers, and stakeholders to put in place policies and interventions targeting vulnerable households for improved and sustained WASH services.

Cumulative health deficits, APOE genotype, and risk for later-life mild cognitive impairment and dementia

ObjectiveTo determine whether health-deficit accumulation is associated with the risks of mild cognitive impairment (MCI) and dementia independently of APOE genotype.MethodsA frailty index was calculated using the deficit-accumulation approach in...

Transitions between cigarette, ENDS and dual use in adults in the PATH study (waves 1–4): multistate transition modelling accounting for complex survey design

IntroductionEven prior to 2018, electronic nicotine delivery systems (ENDS) began to dramatically change the landscape of tobacco products and product use patterns in the USA.MethodsUsing a Markov multistate transition model...

Understanding wealth transitions among households in urban slums of Nairobi: A multi-state transition modelling approach

Disparities in wealth are socially undesirable and may result in economic inequalities that have destabilizing effects on communities. Globally, more than 700 million people who live in extreme poverty still struggle for the most basic human needs. It is important to note that poverty is not static as households and individuals may transition from one wealth state to another with the passage of time. As such, the examination of poverty levels at one point does not offer a sufficiently complete picture of the dynamics in states of wealth through the dimension of time. In this paper, we study transitions in wealth status of households in two informal settlements (slums) in Nairobi, Kenya from 2006 to 2015. We employed the multistate transition model to assess the influence of potential risk factors on wealth transitions for households in urban slums. The results of the analysis indicate that slum areas, age of the household head, ethnicity, gender, household ownership type, food security, and household size have an effect on at least one transition between wealth states. A considerable proportion of households still remain in the lowest and middle wealth states. Households were found to easily transition forward, from the lowest to the highest wealth state than the reverse transition. The estimated mean sojourn times for the lowest, middle and highest wealth tertile were approximately 10, 7, and 14 months, respectively. These highlights the need for interventions that reduce the time spent in the lowest and middle wealth tertile while ensuring retention of households in the highest tertile. Our findings underscore the need for policy options around the provision of economic opportunities with targeted attention to households in vulnerable settings.

Applied Use of Alternate Stable State Modeling in Restoration Ecology

We used multistate transition models of the Everglades ridge and slough landscape to test the application of stable state theory, estimating environmental parameters associated with state changes to develop a quantitative method to measure resilience and stability. The multistate model indicates specific long-term, local hydrology (15-year mean maximums and amplitudes) and edaphic factors that control the local-scale shifts between ridge and slough states. We show that multistate models can provide hydrologic envelopes for managers, produce a tool to help assess future water management scenarios, and address issues of sustainability, resilience, and restoration for any bistable system. These photographs illustrate the article “Applied use of alternate stable state modeling in restoration ecology” by Christa L. Zweig, Sue Newman, and Colin J. Saunders published in Ecological Applications. https://doi.org/10.1002/eap.2195.

Applied use of alternate stable state modeling in restoration ecology.

The concept of alternate stable states is important in ecological theory and models, but the application and implementation of these models have the potential to make significant future advances in the field of patterned landscapes. The bistable ridge and slough landscape is a central feature of Everglades restoration and provides an important opportunity to test stable state theory with multistate transition models. We used these models to estimate environmental parameters associated with state changes (water depths, edaphic factors, etc.) anddevelop a quantitative method to measure resilience and stability. The multistate model indicates that long-term, local hydrology (15-yr mean maximums and 15-yr mean amplitude) and edaphic factors control the local scale shifts between ridge and slough states. We show that multistate models can provide hydrologic envelopes for managers, produce a tool to help assess future water management scenarios, and address issues of sustainability, resilience, and restoration for any bistable system.

Assessing the resilience of multi microgrid based widespread power systems against natural disasters using Monte Carlo Simulation

Abstract The primary objective of this paper is to assess the resilience of a large-scale multi-microgrid based power system to cope with the wide-area natural disasters with severe destructive effects. The proposed resilience assessment method is quantitative and reflects various aspects of power system such as the fragility and uncertainties along with disaster characteristics such as the type and severity. In addition, it is comparable for different power systems and can be used in decision-making by power system operators and planners for future contingency planning and upgrade schemes. The impact of multiple-microgrids is entered in the formulations using the calculation of discrete-time multi-state transition model of the power system in response to an extreme event. The ti N − 1 me-homogeneous Markov chain is considered to determine the probability of system states (normal, microgrid, and emergency) using the time-independent transition matrix. In order to numerically assess the proposed resilience measure, IEEE 30-bus test case and Iceland 189-bus power system are used and simulations are continued by generating 10000 scenarios considering different event type, severity level and location upon the power system. Finally, Monte Carlo Simulation is used for calculating the resilience metrics.

A Quantitative Resilience Measure Framework for Power Systems Against Wide-Area Extreme Events

A framework for quantitative evaluation of the power system resilience considering multimicrogids effects is proposed in this article. The main contribution of the proposed approach is that it incorporates various features underlined in the concept of the power system resilience, such as loss of load probability, expected demand not supplied, system fragility, system recovery difficulties, and system adaption ability after experiencing a destructive event. In addition to the power system aspects, the proposed resilience framework employs the type and severity of natural disasters to achieve realistic results. To model the impact of multiple-microgrids, at first, the discrete-time multistate transition model of the power system under an extreme event is obtained. Then the probability of system states (normal, microgrid, and emergency) is calculated using the time-independent transition matrix and according to the time-homogeneous Markov chain. The effectiveness of the proposed method is tested on the IEEE 30-bus test case and real electricity network of Great Britain in five episodes each with 2000 scenarios.

Recurrent aortic insufficiency after emergency surgery for acute type A aortic dissection with aortic root preservation

ObjectivePatients with acute type A aortic dissection demonstrate a wide range of aortic insufficiency. Outcomes after valve resuspension and root repair are not well studied in the long term. We evaluated the long-term effects of preoperative aortic insufficiency in patients undergoing emergency root-preserving surgery for acute type A aortic dissection. MethodsFrom 2002 to 2017, 558 of 776 patients with acute type A aortic dissection underwent native aortic valve resuspension and root reconstruction. Patients were stratified into 4 groups by preoperative aortic insufficiency grade (n = 539): aortic insufficiency less than 2+ (n = 348), aortic insufficiency = 2+ (n = 72), aortic insufficiency = 3+ (n = 49), and aortic insufficiency = 4+ (n = 70). Multivariable ordinal longitudinal mixed effects and multi-state transition models were used to assess risk factors for recurrent aortic insufficiency. ResultsThe prevalence of cardiogenic shock in patients presenting with preoperative aortic insufficiency less than 2+, 2+, 3+, and 4+ was 53 of 348 (15.2%), 12 of 72 (16.7%), 10 of 49 (20.4%), and 24 of 70 (34.3%), respectively (P = .002). Postoperatively, 94.0% of patients had aortic insufficiency 1+ or less at discharge. Operative mortality was 34 of 348 (9.8%), 10 of 72 (13.9%), 6 of 49 (12.2%), and 12 of 70 (17.1%) (P = .303). In an ordinal mixed effects model, preoperative aortic insufficiency was associated with more severe postoperative aortic insufficiency. The multi-state transition model demonstrated that severe aortic insufficiency was associated with progression from no to mild aortic insufficiency (hazard ratio, 2.14; 95% confidence interval, 1.35-3.38), and progression from mild to moderate aortic insufficiency (hazard ratio, 5.70; 95% confidence interval, 1.88-17.30). ConclusionsPreoperative aortic insufficiency is an important predictor of recurrent aortic insufficiency in patients undergoing valve resuspension with root reconstruction for emergency acute type A aortic dissection repair. Increased echocardiographic surveillance for recurrent aortic insufficiency may be warranted in this cohort.

One Way Out? A Multistate Transition Model of Outcomes After Nursing Home Admission

ObjectivesTo understand how the odds of both adverse and positive transitions vary over the course of episodes of care in nursing homes. DesignRetrospective cohort study of individuals admitted to nursing homes using clinical and administrative Canadian Resident Assessment Instrument version 2 data linked to emergency department and hospital records. Setting and participantsAdults aged 65 years and older, admitted to nursing homes in Ontario, Alberta, British Columbia, and Yukon Territories in Canada, from 2010 to 2015. The sample involved 163,176 individuals with 1,088,336 RAI 2.0 assessments. MeasuresData on mortality and hospitalization were obtained from nursing home and hospital records. Multistate Markov models were employed to estimate odds ratios characterizing covariate effects on transitions to different states of health, hospitalization, and death, stratified by day of stay beginning with the initial 90-day period after admission to a nursing home. ResultsThe first 90 days of stay after admission were characterized by higher odds of both adverse and positive outcomes after adjusting for numerous covariates. Newly admitted residents had greater odds of becoming worse in health instability, being hospitalized, or dying. However, they also had greater odds of being discharged home or improving in health compared with later stages of the episode of care. These associations varied by the resident's Changes in Health, End-Stage Disease, Signs, and Symptoms (CHESS) scores at the start of each 90-day follow-up period, and CHESS was associated with differential rates of death, hospitalization, and discharge home. Conclusions/ImplicationsThe initial 90-day period after nursing home placement is one in which the likelihood of both adverse and positive changes is elevated for nursing home residents. Special efforts must be taken after admission to identify and respond to risk factors that may increase the resident's odds of negative outcomes. At the same time, there may be a window of opportunity for the person's transition back to the community after a brief nursing home stay.

Age Management of Industrial Workers Based on the Multiple Decrement Modelling

Ageing of the workforce and early retirement of industrial workers is influencing a shortage of skilled workers in European industrial systems. Automatic adjustment mechanisms recently introduced in some of the EU member states will increase the retirement age of workers to 71 years until 2060. However, many industrial workers will not be fully productive to the extent of the increased retirement age. Therefore age-productivity profiles, which is an under-researched area, will be of crucial importance for organizations and national policy makers. In this paper, we present a multiple decrement model of workforce transitions and exits, related to age-productivity profiles of industrial workers. Based on this model, we present the calculation of the expected duration of working life and study the drivers that influence transitions among different states of productivity and exits from the workforce, which have not been developed yet. The workforce availability in ageing economies can be influenced by implementing appropriate age management practices, where workplace ergonomics and smart production cells are playing an increasingly important role. This paper introduces the expected duration of work-life based on an actuarial multi-state transition model as a measure of the quality of the organizational age management systems and serves as a policy tool for taking corrective actions at the organizational and national level. The numerical example is based on data from the Statistical office of the Republic of Slovenia.