Multistate Approach Research Articles

A multistate modeling approach to investigate long-term effects of claw horn disruption lesions and early lesion development in dairy cows

Claw horn disruption lesions (CHDL) are a leading cause of lameness in dairy cattle, and the development, effect, and pathology of these lesions remains an open area of interest within dairy cattle health. Current literature typically attempts to measure the effect of risk factors on the development of CHDL over a relatively short time period. Further understanding of the interaction of CHDL and the long-term effect of early CHDL in a cow's life remains an important area of research which is so far mostly unexplored. In this study 57,974 cows from 1,332 herds were selected and their regular claw trimming records containing important claw health information were used to model the long-term effect of lesions in a cow's lifetime in a 6-state multistate model. A multistate model predicts the time before transition from any one state to another and the probability of transition to a future state. The 6 lesion states that were modeled were as follows: never had a lesion, first recorded lesion event, no recorded lesion after first lesion event, second or subsequent recorded lesion event, no recorded lesion after second or subsequent lesion event, and culled. The effect of various cow level covariates on the transition probabilities between various states was tested. For the first time, this study shows the importance and effect of the first lesion and other cow level factors on long-term claw health. Model results showed that the timing and severity of the first recorded lesion event significantly influenced the likelihood of a future lesion being present. Cows with CHDL present within the 180 d of first calving had a short-term increased risk and long-term decreased risk of a future lesion, compared with cows that present with CHDL later than 180 d of first lactation. Moreover, presence of a severe first lesion increased a cow's risk of a future lesion being present. The model was used to evaluate the relative difference between high-risk cows (age of first calving ≥793 d, breeding values in the lowest quartile) and low-risk cows (age of first calving ≤718 d, breeding values in the highest quartile). Our results indicated that these low-risk cows present with a lesion on an average 3 mo later than high-risk cows. Furthermore, results from the model evaluation of a simulated herd with cows with breeding values in the higher quartile indicated that cows present with a CHDL on an average 7.5 mo later compared with a herd where cows have breeding values distributed in a lower quartile.

Projecting Long-Term Care Costs for Home and Community-Based Services in China from 2005 to 2050.

The aim of this study was to estimate and project the trend in long-term care (LTC) costs for home and community-based services as a percentage of gross domestic product in China between 2005 and2050. Longitudinal. We used 61,249 observations from 37,702 adults age ≥65years from waves 2005, 2008, 2011, 2014, and 2018 of the Chinese Longitudinal Healthy Longevity Surveys. LTC costs for home and community-based services consisted of the monetary value of time spent on LTC and the direct LTC cost. We used the age-sex-residence-specific weights provided by the Chinese Longitudinal Healthy Longevity Surveys to estimate the LTC costs from 2005 to 2018. We used a component-based model to project LTC costs, in which the 2-part model was used to estimate the average LTC costs and the multi-state Markov model approach was used to project the future population by age, sex, and disability state. The percentage of older adults with disabilities was projected to increase from 6.1% in 2005 to 7.5% in 2020 and 9.6% in 2050. The total LTC cost for home and community-based services were projected to increase from 0.3% of gross domestic product in 2005 to 0.7% in 2020 and to 6.4% in2050. Policymakers in China should take urgent actions to delay the onset of disabilities among older adults, which would curb the increasing LTC costs and maintain the sustainability of the LTC policies.

A connection between survival multistate models and causal inference for external treatment interruptions.

Recently, treatment interruptions such as a clinical hold in randomized clinical trials have been investigated by using a multistate model approach. The phase III clinical trial START (Stimulating Targeted Antigenic Response To non-small-cell cancer) with primary endpoint overall survival was temporarily placed on hold for enrollment and treatment by the US Food and Drug Administration (FDA). Multistate models provide a flexible framework to account for treatment interruptions induced by a time-dependent external covariate. Extending previous work, we propose a censoring and a filtering approach both aimed at estimating the initial treatment effect on overall survival in the hypothetical situation of no clinical hold. A special focus is on creating a link to causal inference. We show that calculating the matrix of transition probabilities in the multistate model after application of censoring (or filtering) yields the desired causal interpretation. Assumptions in support of the identification of a causal effect by censoring (or filtering) are discussed. Thus, we provide the basis to apply causal censoring (or filtering) in more general settings such as the COVID-19 pandemic. A simulation study demonstrates that both causal censoring and filtering perform favorably compared to a naïve method ignoring the external impact.

(Healthy) Aging Patterns in Europe: A Multistate Health Transition Approach

We explore patterns and determinants of health transition probabilities by combining outcomes of morbidity and mortality to examine different aging patterns across Europe, and to ascertain how individual socio-demographic characteristics modify these patterns. We use panel data from the Survey of Health, Ageing and Retirement in Europe (2004– 2017) for 76,536 individuals aged 50 + in 20 European countries who participated in at least two waves. All transition probabilities were calculated applying a multistate analytical approach. Our findings show significant gender, education, and cohort differences in health transition probabilities and marked cross-country group differences. Central and Northern European countries present lower probabilities of health deterioration than Southern and, especially, Eastern European countries. Having a high level of education, living in Central Europe, and being younger are associated with lower probabilities of health deterioration and, if any, a higher probability of being restored to good health. We found less evidence of differences when transitions end in death. Our study contributes to this line of research by implementing a multistate approach using European harmonized panel dataset, to examine the effects of birth cohort, educational attainment and gender differences on health transitions. Our findings point to the need to consider the specific influence of individual factors in the aging process in different transitions according to the context and with reference to specific vulnerable groups. In the context of aging societies, such a consideration is both essential and policy relevant.

Partnership and fertility trajectories of immigrants and descendants in the United Kingdom: A multilevel multistate event history approach

We study the interrelationships between partnership and fertility trajectories of immigrant women and female descendants of immigrants using the UK Household Longitudinal Study. We propose a novel multistate event history approach to analyse the outcomes of unpartnered, cohabiting, and married women. We find that the partnership and fertility behaviours of immigrants and descendants from European and Western countries are similar to those of native women: many cohabit first and then have children and/or marry. Those from countries with conservative family behaviours (e.g. South Asian countries) marry first and then have children. Women from the Caribbean show the weakest link between partnership changes and fertility: some have births outside unions; some form a union and have children thereafter. Family patterns have remained relatively stable across migrant generations and birth cohorts, although marriage is being postponed in all groups. Our findings on immigrants support the socialization hypothesis, whereas those on descendants are in line with the minority subculture hypothesis.

Impact of the Kidney Transplantation Moratorium in France Because of the COVID-19 Pandemic: A Cohort-based Study.

The COVID-19 pandemic has resulted in worldwide kidney transplantation (KT) moratoriums. The impacts of these moratoriums on the life expectancy of KT candidates remain unclear. We simulated the evolution of several French candidate populations for KT using a multistate semi-Markovian approach and according to moratorium durations ranging from 0 to 24 mo. The transition rates were modeled from the 63 927 French patients who began dialysis or were registered on the waiting list for KT between 2011 and 2019. Among the 8350 patients active on the waiting list at the time of the French KT moratorium decided on March 16, 2020, for 2.5 mo, we predicted 4.0 additional months (confidence interval [CI], 2.8-5.0) on the waiting list and 42 additional deaths (CI, -70 to 150) up to March 16, 2030, compared with the scenario without moratorium. In this population, we reported a significant impact for a 9-mo moratorium duration: 135 attributable deaths (CI, 31-257) up to March 16, 2030. Patients who became active on the list after March 2020 were less impacted; there was a significant impact for an 18-mo moratorium (175 additional deaths [CI, 21-359]) in the 10 862 prevalent end-stage renal disease patients on March 16, 2020 and for a 24-mo moratorium (189 additional deaths [CI, 10-367]) in the 16 355 incident end-stage renal disease patients after this date. The temporary moratorium of KT during a COVID-19 peak represents a sustainable decision to free up hospitals' resources if the moratorium does not exceed a prolonged period.

Inequalities in Retirement Life Span in the United States.

The length of retirement life may be highly unequal due to persistent and significant discrepancies in old-age mortality. This study assesses gender and educational differences in the average retirement life span and the variation in retirement life span, taking into account individual labor force exit and reentry dynamics. We used longitudinal data from the Health and Retirement Study from 1996 to 2016, focusing on respondents aged 50 and older (N=32,228). Multistate life tables were estimated using discrete-time event history models. The average retirement life span, as well as absolute and relative variation in retirement life span, were calculated analytically. Among women, we found a persistent educational gradient in average retirement life span over the whole period studied; among men, the relationship between education and retirement expectancy differed across periods. Women and the lower-educated had higher absolute variation in retirement life span than men and the higher-educated-yet these relationships were reversed when examined by relative variation. Our multistate approach provides an accurate and comprehensive picture of the retirement life span of older Americans over the past two decades. Such findings should be considered in high-level discussions on Social Security. Potential reforms such as raising the eligibility age or cutting benefits may have unexpected implications for different social groups due to their differential effects on retirement initiation and reentry dynamics.

Impact of the kidney transplantation moratorium in France because of the COVID-19 pandemic

Abstract Background The COVID-19 pandemic has resulted in worldwide kidney transplantation (KT) moratoriums. The impacts of these moratoriums on the life expectancy of KT candidates remain unclear. Methods We simulated the evolution of several French candidate populations for KT using a multistate semi-Markovian approach and according to moratorium durations ranging from 0 to 24 months. The transition rates were modeled from the 63,927 French patients who began dialysis or were registered on the waiting list for KT between 2011 and 2019. Results Among the 8,350 patients active on the waiting list at the time of the French KT moratorium decided on March 16, 2020, for 2.5-months, we predicted 4.0 additional months [CI: 2.8, 5.0] on the waiting list and 42 additional deaths [CI: -70, 150] up to March 16, 2030. In this population, we reported a significant impact for a 9-month moratorium duration: 135 attributable deaths [CI: 31, 257] up to March 16, 2030. Patients who became active on the list after March 2020 were less impacted. Interpretation The temporary moratorium of KT during a COVID-19 peak in order to free up hospitals’ resources doesn't impact patients’ 10-year survival if the moratorium does not exceed a prolonged period. Funding. French National Research Agency (ANR-20-COV8-0002-01). Key messages

Excess length of stay and readmission following hospital-acquired bacteraemia: a population-based cohort study applying a multi-state model approach

ObjectivesPopulation-based estimates of excess length of stay after hospital-acquired bacteraemia (HAB) are few and prone to time-dependent bias. We investigated the excess length of stay and readmission after HAB. MethodsThis population-based cohort study included the North Denmark Region adult population hospitalized for ≥48 hours, from 2006 to 2018. Using a multi-state model with 45 days of follow-up, we estimated adjusted hazard ratios (aHRs) for end of stay and discharge alive. The excess length of stay was defined as the difference in residual length of stay between infected and uninfected patients, estimated using a non-parametric approach with HAB as time-dependent exposure. Confounder effects were estimated using pseudo-value regression. Readmission after HAB was investigated using the Cox regression. ResultsWe identified 3457 episodes of HAB in 484 291 admissions in 205 962 unique patients. Following HAB, excess length of stay was 6.6 days (95% CI, 6.2–7.1 days) compared with patients at risk. HAB was associated with decreased probability of end of hospital stay (aHR, 0.60; 95% CI, 0.57–0.62) driven by the decreased hazard for discharge alive; the aHRs ranged from 0.30 (95% CI, 0.23–0.40) for bacteraemia stemming from ‘heart and vascular’ source to 0.72 (95% CI, 0.69–0.82) for the ‘urinary tract’. Despite increased post-discharge mortality (aHR, 2.76; 95% CI, 2.38–3.21), HAB was associated with readmission (aHR, 1.42; 95% CI, 1.31–1.53). ConclusionHAB was associated with considerably excess length of hospital stay compared with hospitalized patients without bacteraemia. Among patients discharged alive, HAB was associated with increased readmission rates.

A multistate modeling approach for organizational cybersecurity exploration and exploitation

This study examines the dynamic stages of exploration and exploitation efforts by organizations in their cybersecurity responses using multistate modeling. Using textual data from the annual 10-K reports of S&P 100 organizations, this study uses a combination of text analytics and Markov chain approach to quantify exploration and exploitation in organizational cybersecurity responses. The study models two and four states of exploration and exploitation based on their cybersecurity responses over time and uses a continuous-time Markov chain approach to analyze transitions between states as organizations adapt their responses over time to achieve ambidexterity. The two-state Markov model focuses on the firm-level Exploration and Exploitation states whereas the four-state model captures deeper levels of exploration and exploitation by considering Surviving, Investigating, Reinforcing, and Balancing as possible states for exploration and exploitation of cybersecurity responses. We analyze the dynamics of organizational exploration-exploitation behaviors by modeling longitudinal transition probabilities across different states. Implications for research and practice are discussed.

Patient trajectories after diagnosis of diffuse large B-cell lymphoma—a multistate modelling approach to estimate the chance of lasting remission

BackgroundAchieving lasting remission for at least 2 years is a good indicator for favourable prognosis long term after Diffuse large B-cell lymphoma (DLBCL). The aim of this study was to provide real-world probabilities, useful in risk communication and clinical decision-making, of the chance for lasting remissions by clinical characteristics.MethodsDLBCL patients in remission after primary treatment recorded in the Swedish Lymphoma register 2007–2014 (n = 2941) were followed for relapse and death using multistate models to study patient trajectories. Flexible parametric models were used to estimate transition rates.ResultsAt 2 years, 80.7% (95% CI: 79.0–82.2) of the patients were predicted to remain in remission and 13.2% (95% CI: 11.9–14.6) to have relapsed. The relapse risk peaked at 7 months, and the annual decline of patients in remission stabilised after 2 years. The majority of patients in the second remission transitioned into a new relapse. The probability of a lasting remission was reduced by 20.4% units for patients with IPI 4–5 compared to patients with IPI 0–1, and time in remission was shortened by 3.5 months.ConclusionThe long-term prognosis was overall favourable with 80% achieving durable first remissions. However, prognosis varied by clinical subgroups and relapsing patients seldom achieved durable second remissions.

Use of statins after liver transplantation is associated with improved survival: results of a nationwide study.

SummaryBackgroundThere is limited information on the effects of statins on the outcomes of liver transplantation (LT), regarding either their use by LT recipients or donors.AimTo analyse the association between statin exposure and recipient and graft survival.MethodsWe included adult LT recipients with deceased donors in a nationwide prospective database study. Using a multistate modelling approach, we examined the effect of statins on the transition hazard between LT, biliary and vascular complications and death, allowing for recurring events. The observation time was 3 years.ResultsWe included 998 (696 male, 70%, mean age 54.46 ± 11.14 years) LT recipients. 14% of donors and 19% of recipients were exposed to statins during the study period. During follow‐up, 141 patients died; there were 40 re‐LT and 363 complications, with 66 patients having two or more complications. Treatment with statins in the recipient was modelled as a concurrent covariate and associated with lower mortality after LT (HR = 0.35; 95% CI 0.12–0.98; p = 0.047), as well as a significant reduction of re‐LT (p = 0.004). However, it was not associated with lower incidence of complications (HR = 1.25; 95% CI = 0.85–1.83; p = 0.266). Moreover, in patients developing complications, statin use was significantly associated with decreased mortality (HR = 0.10; 95% CI = 0.01–0.81; p = 0.030), and reduced recurrence of complications (HR = 0.43; 95% CI = 0.20–0.93; p = 0.032).ConclusionsStatin use by LT recipients may confer a survival advantage. Statin administration should be encouraged in LT recipients when clinically indicated.

Predictors of Intensive Care Unit Stay in Patients with Acute Traumatic Spinal Cord Injury Above T6

The objective of this study was to identify factors associated with the intensive care unit (ICU) length of stay (LOS) of patients with an acute traumatic spinal cord injury above T6. We performed a retrospective, observational study of patients admitted to an ICU between 1998 and 2017 (n= 241). The LOS was calculated using a cumulative incidence function, with events of death being considered a competing event. Factors associated with the LOS were analyzed using both a cause-specific Cox proportional hazards regression model and a competing risk model. A multistate approach was also used to analyze the impact of nosocomial infections on the LOS. A total of 211 patients (87.5%) were dischargedalive from the ICU (median LOS=23days), and 30 (12.4%) died (median LOS=11days). In the multivariate analysis after adjusting for variables collected 4days after the ICU admission, a higher American Spinal Injury Association motor score (subdistribution hazards ratio [sHR]=1.01), neurological level C5-C8 (HR=0,64), and lower Sequential Organ Failure Assessment score (sHR=0.82) and fluid balance (sHR=0.95) on day 4 were linked to a lower LOS in this unit. In the multivariate analysis, the onset of an infection was significantly associated with a longer LOS when adjusting for variables collected both at ICU admission (adjusted sHR=0.62; 95% confidence interval=0.50-0.77) and on day 4 (adjusted hazards ratio=0.65; 95% confidence interval=0.52-0.80). After adjusting the data for conventional variables, we identified a lower American Spinal Injury Association motor score, injury level C5-C8, a higher Sequential Organ Failure Assessment score on day 4, a more positive fluid balance on day 4, and the onset of an infection as factors independently associated with a longer ICU LOS.

Prognosis and recurrence patterns in patients with early stage lung cancer: a multi-state model approach.

BackgroundWe aimed to assess whether recurrence patterns affect survival and to use a multi-state model to predict the prognosis of early stage non-small cell lung cancer in patients who underwent surgical resection.MethodsPatients with early stage non-small cell lung cancer who underwent surgical resection at two tertiary medical centers between 2010 and 2015 were retrospectively analyzed. A multi-state model was employed with one initial state (surgery), two intermediate states (locoregional recurrence, distant metastasis), and one absorbing state (death), comprising five transitions: surgery to locoregional recurrence, surgery to distant metastasis, surgery to death without recurrence, locoregional recurrence to death, and distant metastasis to death. Cox proportional hazards models stratified for these transitions were performed with the risk factors; transition probabilities for each patient were predicted.ResultsA total of 949 patients were identified [median age: 67 years, male: 614 (64.6%)]. Recurrence occurred in 194 (20.4%) patients (locoregional recurrence: 7.3%, distant metastasis: 13.1%). Hazard ratios for distant metastasis after surgery were higher for older age (hazard ratio: 1.03, 95% confidence interval: 1.01–1.06) and adenocarcinoma (hazard ratio: 1.67, 95% confidence interval: 1.06–2.61). Lower lobe location exhibited a higher hazard ratio for death after surgery without recurrence (hazard ratio: 1.59, 95% confidence interval: 1.00–2.53). Stage IIB lung cancer showed a higher probability of transition to distant metastasis after surgery than other stages. Cumulative transition hazards rapidly increased in both recurrence patterns until approximately two years after surgery (locoregional recurrence: 0.052; distant metastasis: 0.104). Patients with distant metastasis were more likely to die within 5 years of surgery than those with locoregional recurrence (6.8% and 2.6%, respectively).ConclusionsWith the multi-state model, risk factors and post-relapse survival probabilities differed between locoregional recurrence and distant metastasis. These findings may enable clinicians to establish personalized follow-up strategies for patients undergoing curative resection for early stage non-small cell lung cancer.

Similarity of competing risks models with constant intensities in an application to clinical healthcare pathways involving prostate cancer surgery

The recent availability of routine medical data, especially in a university-clinical context, may enable the discovery of typical healthcare pathways, that is, typical temporal sequences of clinical interventions or hospital readmissions. However, such pathways are heterogeneous in a large provider such as a university hospital, and it is important to identify similar care pathways that can still be considered typical pathways. We understand the pathway as a temporal process with possible transitions from a single initial treatment state to hospital readmission of different types, which constitutes a competing risks setting. In this article, we propose a multi-state model-based approach to uncover pathway similarity between two groups of individuals. We describe a new bootstrap procedure for testing the similarity of constant transition intensities from two competing risk models. In a large simulation study, we investigate the performance of our similarity approach with respect to different sample sizes and different similarity thresholds. The studies are motivated by an application from urological clinical routine and we show how the results can be transferred to the application example.

A multi-stable isotopic constraint on water column oxygen sinks in the Pearl River Estuary, South China

Bottom water oxygen depletion is a central concern in estuaries and coastal oceans worldwide. However, a mechanistic understanding and quantitative diagnosis of different oxygen-consuming processes are less clear. In this study, a multi-stable isotope approach is developed to delineate the role of oxygen respiration and nitrification contributing to total oxygen consumption in the Pearl River Estuary (PRE), a large eutrophic estuary in south China. The approach highly couples with analysis of the carbon isotope composition of dissolved inorganic carbon (δ13C-DIC) and with stable nitrogen isotope analysis in ammonium (δ15N-NH4+) and nitrate (δ15N-NO3−). In all seasons, relatively low DO concentrations were observed in the upper reach and, to some extent, in the outer estuary during summer, while high concentrations of DO were found in the transition zone between the inner and outer estuary. On the basis of isotopic differentiation, our data reveal that much more depleted δ13C-DIC is coincident with DIC additions and low oxygen in the upper reach and inner estuary during most seasons. This is most likely a consequence of organic carbon (OC) degradation via aerobic respiration. Based on the carbon isotopic mass balance of DIC and the stoichiometry ratio of −ΔDO/ΔDIC, we found that the OC degradation dominates the total oxygen consumption in the upper reach, as well as in the inner estuary during summer (48.3%–93.5%). In addition, nitrification is another key process in contributing to total oxygen loss in the upper reach, as supported by the well-coupled variations of δ15N of NH4+ and NO3− and apparent oxygen utilization (AOU). Using the formerly determined N isotopic fractionation and observed δ15N variation, we estimated that nitrification could account for 35.3%–44.1% and 28.5%–31.6% of the total oxygen consumption in the upper reach during winter and summer, respectively, while its contribution to total oxygen loss is minor in the inner and outer estuary. Overall, this study demonstrates the potential of the multi-stable isotopic approach to assess oxygen sink partitioning in large human-perturbed estuaries.

Changes in Health Expectancy for Older Adults in Japan: Results from Two Longitudinal Surveys

Background: Although there is evidence of improvements in health expectancy among the Japanese population, existing estimates are based on the prevalence of morbidity taken from cross-sectional survey data. Objectives: This study employed a multistate life table approach to compute incidence-based health expectancy measures, namely active and inactive life expectancy (LE), for two longitudinal survey cohorts from 1990 to 2009. Methods: This study used data from two longitudinal surveys of older adults in Japan: the National Survey of the Japanese Elderly (1990–1999) and the Nihon University Japanese Longitudinal Study of Aging (1999–2009). We employed the Interpolation of Markov Chains technique to compute the number of years at age 65 years to be spent with and without difficulty in performing activities of daily living (ADLs) or instrumental ADLs. Results: We documented significant increases in active LE for men and women at age 65 years over the 10-year study period. There were significant changes in total LE for men and in the percentage of active life for women. Inactive LE did not significantly change across the two survey cohorts during the study period. Conclusions: Our results show that the health status of older adults in Japan has largely improved over the 10-year study period, with increases in both the duration of life and time spent in an active state. This finding offers evidence of compression of morbidity among older men and women in Japan.

Graph-Based Dynamic Modeling of Two-Phase Heat Exchangers in Vapor Compression Systems

Vapor compression systems are a popular thermal management solution for high heat load applications because they benefit from the high heat transfer rate of two-phase fluid flow. However, model-based design and control of these systems proves challenging because of the complex and coupled hydro-thermal dynamics as the working fluid changes phase in the heat exchangers. When modeling these heat exchangers, there exists a strong tradeoff between model accuracy and computational complexity. While different techniques have aimed to reduce computational complexity of the model, they come at the cost of a decrease in accuracy. On the other hand, high fidelity models are computationally expensive to run. To bridge the gap between computational efficiency and accuracy, this work develops a novel multi-state graph-based dynamic modeling approach. The multi-state graph modeling approach is used to develop a dynamic model of a two-phase heat exchanger. The heat exchanger model is integrated into a vapor compression system model and the model behavior is verified against other models present in the literature. The results demonstrate that the multi-state graph model can accurately capture system dynamics within 1% of the current state of the art modeling approaches while providing valuable modularity for system level modeling. Additionally, the computational load can be made comparable to less accurate approaches.

Incidence and mortality of hospital-acquired bacteraemia: a population-based cohort study applying a multi-state model approach

ObjectiveThe effect of hospital-acquired bacteraemia on mortality is sparsely investigated. We investigated the incidence and hospital-acquired bacteraemia impact on mortality. MethodsWe conducted a 13-year population-based cohort study using the North Denmark Bacteraemia Research Database and Danish health registries. The population comprised all adult patients with a hospital admission lasting ≥48 hr. We used Poisson regression to estimate trends in incidence. The 30-day mortality of hospital-acquired bacteraemia was estimated using an illness-death multistate model with recovery using the population at risk of hospital-acquired bacteraemia as reference. ResultsWe identified 3588 episodes of hospital-acquired bacteraemia in 484 264 admissions. The incidence increased proportionally by 1.02 episodes yearly (95% CI 1.01–1.03) between 2006 and 2018. Hospital-acquired bacteraemia was associated with increased mortality (adjusted hazard ratio (aHR) 4.32, 95% CI 3.95–4.72), especially hospital-acquired bacteraemia with unknown source (aHR 6.42 (95% CI 5.67–7.26), “thoracic incl. pneumonia” (aHR 5.89, 95% CI 3.45–10.12) and abdominal source (aHR 4.33, 95% CI 3.27–5.74). The relative impact on mortality diminished with age (aHR 5.66, 95% CI 2.00–16.01 in 18–40 years old vs. 3.69, 95% CI 3.14–4.32 in 81–105 years old) and comorbidity (aHR 5.75, 95% CI 4.45–7.42 in low vs. 3.55, 95% CI 3.16–3.98 in high comorbidity), and was higher in elective admissions (aHR 9.09, 95% CI 7.14–11.57 vs. aHR of 4.03, 95% CI 3.67–4.42). DiscussionHospital-acquired bacteraemia is associated with high mortality, especially when the source is unknown or originating from the thoracic cavity.

The effect of antiviral treatment on SARS-CoV-2 infectious disease progression: A comparison of the multi-state models

Combating SARS-CoV-2 is the first concern and goal of the whole world faced with the global health crisis. Since 2019, the SARS-CoV-2 infection (COVID-19) and even mutated infection cases have been increasing rapidly. From 2019 through 27 August 2021, a total of 214,468,601 individuals were confirmed cases of SARS-CoV-2, including 4,470,969 death toll. Some of these individuals were able to access treatment and some could not, but for a while there was complete uncertainty. It was not known whether those who accessed treatment were lucky, but treatment was based on trial and error because of this uncertainty around the world until data was collected. Therefore, the aim of this study was to model SARS-CoV-2 infectious disease progression from the date of polymerase chain reaction (PCR) test to the date of negative outcome via Bayesian multi-state model approaches considering risk factors such as gender, age, and antiviral treatment. Data from 746 inpatients were collected from August 1st until the December 1st, 2020. For the multi-state model, five various discrete states were selected according to the Republic of Turkey Ministery of Health treatment algorithm. The results showed that Bayesian multi-state models with the Weibull distributed baseline hazard function were more appropriate models in the presence of risk factors and antiviral treatment.