Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells?

Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term "invasive lobular carcinoma" implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial-mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.

Dynamics of detailed components of metabolic syndrome associated with the risk of cardiovascular disease and death.

Few studies quantify a cascade of dynamic transitions on the detailed components of metabolic syndrome (MetS) and subsequent progressions to cardiovascular disease (CVD) and its death. A total of 47,495 subjects repeatedly attending a community-based integrated screening program in Taiwan were recruited. The refined MetS-related classification (RMRC) in relation to five criteria of MetS was defined as free of metabolic disorder (FMD, none of any criteria), mild metabolic disorder (MMD, 1-2 criteria) and MetS. A multistate Markov model was used for modelling such a multistate process. The estimated progression rate from FMD to MMD was 44.82% (95% CI 42.95-46.70%) whereas the regression rate was estimated as 29.11% (95% CI 27.77-30.45%). The progression rate from MMD to MetS was estimated as 6.15% (95% CI 5.89-6.42%). The estimated annual incidence rates of CVD increased with the severity of RMRC, being 1.62% (95% CI 1.46-1.79%) for FMD, 4.74% (95% CI 4.52-4.96%) for MMD, to 20.22% (95% CI 19.52-20.92%) for MetS. The estimated hazard rate of CVD death was 6.1 (95% CI 4.6-7.7) per thousand. Elucidating the dynamics of MetS-related transition and quantifying the incidence and prognosis of CVD provide a new insight into the design and the evaluation of intervention programs for CVD.

Incidence, Prevalence, and Duration of Chronic Kidney Disease in Taiwan: Results from a Community-Based Screening Program of 106,094 Individuals.

BACKGROUND/AIMS: Taiwan has the highest incidence of end-stage renal disease, which requires renal replacement therapy. Chronic kidney disease (CKD) contributes to this burden. However, the current data on the epidemiologic features of CKD in Taiwan are incomplete. Therefore, we aimed to investigate the prevalence and incidence of CKD in a population-based study and then estimate the average dwelling time (ADT) in the main clinical burden of CKD (stages 3-5). METHODS: A prospective cohort study was designed with an integrated community-based multiple screening program of 106,094 individuals aged ≥20 years in Keelung, Taiwan, in 1999-2009. Prevalence was estimated as the percentage of CKD stages among individuals attending the first screening, and incidence was expressed as the ratio of total desired events in the following period to the total observational time. Finally, ADT was estimated from the ratio of prevalence to incidence. RESULTS: The participants' mean age was 47.7 ± 15.4 years. The estimated prevalence was 15.46% for total CKD and 9.06% for CKD stages 3-5. The incidence was 27.21/1,000 person-years (PY) for total CKD and 16.89/1,000-PY for CKD stages 3-5. Older patients, males, and those patients with comorbidities of diabetes mellitus (DM), hypertension, and metabolic syndrome (MetS) exhibited higher prevalence and incidence rates than their opposing counterparts. Moreover, the ADT of CKD stages 3-5 was 5.37 years (95% CI 5.17-5.57). Males and those with comorbidities of DM or MetS had shorter ADTs in CKD stages 3-5 than their opposing counterparts. Interestingly, the ADT of participants with hypertension was longer than those without. CONCLUSIONS: The prevalence and incidence of CKD in Taiwan are high. Moreover, ADT in CKD stages 3-5 varied according to sex, age, and comorbidity. Further exploration of the factors associated with the shifting of this duration will shed light on effective CKD management.

Bayesian negative-binomial-family-based multistate Markov model for the evaluation of periodic population-based cancer screening considering incomplete information and measurement errors.

Population-based cancer screening is often asked but hardly addressed by a question: "How many rounds of screening are required before identifying a cancer of interest staying in the pre-clinical detectable phase (PCDP)?" and also a similar one related to the number of screens required for stopping screening for the low risk group. It can be answered by using longitudinal follow-up data on repeated rounds of screen, namely periodic screen, but such kind of data are rather complicated and fraught with intractable statistical properties including correlated multistate outcomes, unobserved and incomplete (censoring or truncation) information, and imperfect measurements. We therefore developed a negative-binomial-family-based discrete-time stochastic process, taking sensitivity and specificity into account, to accommodate these thorny issues. The estimation of parameters was implemented with Bayesian Markov Chain Monte Carlo method. We demonstrated how to apply this proposed negative-binomial-family-based model to the empirical data similar to the Finnish breast cancer screening program.

Impact of Comorbidity on Fatality Rate of Patients with Middle East Respiratory Syndrome.

To date, 1841 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported worldwide, with 652 deaths. We used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of Middle East respiratory syndrome (MERS) cases up to the end of October 2016. A Bayesian Weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatality rate of MERS cases and its variation across countries. The crude fatality rate of MERS cases was 32.1% (95% credibility interval (CI): 29.9%, 34.3%). Notably, the incremental change of daily death rate was most prominent during the first week since disease onset with an average increase of 13%, but then stabilized in the remaining two weeks when it only increased 3% on average. Neither sex, nor country of infection were found to have a significant impact on fatality rates after taking into account the age and comorbidity status of patients. After adjusting for age, epidemic period, MERS patients with comorbidity had around 4 times the risk for fatal infection than those without (adjusted hazard ratio of 3.74 (95% CI: 2.57, 5.67)).

Effects of tooth extraction on smile esthetics and the buccal corridor: A meta-analysis.

BACKGROUND/PURPOSE: Smile esthetics is a critical factor for evaluating orthodontic treatment outcomes. The effects of tooth extraction on smile esthetics and buccal corridor remain controversial and have not been adequately investigated. Therefore, in this systematic review and meta-analysis, we evaluated the aforementioned effects. MATERIALS AND METHODS: We searched clinical studies held in PubMed, MEDLINE, Embase, and the Cochrane Library up to May 2015, with no restriction. Study selection and data extraction were conducted by two reviewers independently. A random-effects model was used for conducting a meta-analysis to assess the mean difference between the esthetic score and the buccal corridor ratio of extraction and nonextraction groups. RESULTS: Six eligible studies were included in this meta-analysis. No significant difference was observed in the esthetic score and the buccal corridor ratio between extraction and nonextraction groups. CONCLUSION: Tooth extraction does not affect smile esthetics or buccal corridor. However, additional detailed, large-scale, double-blinded, and randomized controlled trials are required for further evaluation.

XRCC1 Gene Polymorphism, Clinicopathological Characteristics and Stomach Cancer Survival in Thailand.

BACKGROUND: Stomach cancer is one of leading causes of death worldwide. In Thailand, the incidence and mortality of stomach cancer are in the top ten for cancers. Effects of DNA repair gene X-ray repair cross complementary protein 1 (XRCC1) polymorphisms and clinicopathological characteristics on survival of stomach cancer in Thailand have not been previously reported. The aim of this study was to investigate the effects of XRCC1 gene and clinicopathological characteristics on survival of stomach cancer patients in Thailand. MATERIALS AND METHODS: Data and blood samples were collected from 101 newly diagnosed stomach cancer cases pathologically confirmed and recruited during 2002 to 2006 and followed-up for vital status until 31 October 2012. Genotype analysis was performed using real-time PCR-HRM. The data were analyzed using the Kaplan-Meier method to yield cumulative survival curve, log-rank test to assess statistical difference of survival and Cox proportional hazard models to estimate adjusted hazard ratio. RESULTS: The total followed-up times were 2,070 person-months, and the mortality rate was 4.3 per 100 person-months. The median survival time after diagnosis was 8.07 months. The cumulative 1-, 3-, 5-years survival rates were 40.4%, 15.2 % and 10.1 % respectively. After adjustment, tumour stage were associated with an increased risk of death (p= 0.036). The XRCC1 Gln339Arg, Arg/Arg homozygote was also associated with increased risk but statistically this was non-significant. CONCLUSIONS: In addition to tumour stage, which is an important prognostic factor affecting to the survival of stomach cancer patients, the genetic variant Gln339Arg in XRCC1 may non-significantly contribute to risk of stomach cancer death among Thai people. Larger studies with different populations are need to verify ours findings.

Sites of peripheral artery occlusive disease as a predictor for all-cause and cardiovascular mortality in chronic hemodialysis.

BACKGROUND: The ankle-brachial blood pressure (BP) index (ABI) not only indicates the presence of peripheral artery occlusive disease (PAOD) but predicts mortality in patients undergoing hemodialysis (HD). However, whether the site of PAOD can provide additional contribution to predicting mortality have not been investigated yet. Our primary objective was to determine the associations between the site of PAOD and all-cause and cardiovascular mortality in chronic HD (CHD) patients. METHODS: A retrospective cohort study was conducted to evaluate 444 Taiwanese CHD patients between December 2006 and June 2013. The site of PAOD together with other explanatory variables such as demographic data, body mass index, a history of cardiovascular diseases, HD vintage, biochemical data, and cardiothoracic ratio (CTR) were assessed by the Cox proportional hazards regression model. RESULTS: The frequency of PAOD was 14.6% in both legs, 4.9% in the right side only, and 5.1% in the left side only. During the study period, 127 all-cause and 93 cardiovascular deaths occurred. PAOD site was found to have significant predictive power for all-cause mortality with the order of 3.04 (95% CI: 1.56-5.90) hazard ratio on the right side, 2.48 (95% CI: 1.27-4.82) on the left side, and 4.11 (95% CI: 2.76-6.13) on both sides. The corresponding figures for cardiovascular mortality were 3.81 (95% CI: 1.87-7.76) on the right side, 2.76 (95% CI: 1.30-5.82) on the left side, and 3.95 (95% CI: 2.45-6.36) on both sides. After adjustment for other explanatory variables, only right-sided PAOD still remained to have significant predictive power for all-cause and cardiovascular mortality and bilateral PAOD kept the significant association with all-cause mortality. CONCLUSIONS: The site of PAOD revealed various predictive powers for all-cause and cardiovascular mortality in CHD patients and only right-sided PAOD remained an independent predictor for both types of mortality making allowance for relevant confounding factors.

Fuzzy set regression method to evaluate the heterogeneity of misclassifications in disease screening with interval-scaled variables: application to osteoporosis (KCIS No. 26).

Although the trade-off between the two misclassifications (false-positive fraction and false-negative fraction), corresponding to type I and type II error in statistical hypothesis testing based on Neyman-Pearson lemma, to determine the optimal cutoff in the province of evaluating the accuracy of medical diagnosis and disease screening using interval-scaled biomarkers has been attempted by the receiver operating characteristic (ROC) curve, the heterogeneity of the two misclassifications in relation to the utility or individual preference for relative weights between the two errors has been barely addressed and has increasingly gained attention in disease screening when the optimal subject-specific or subgroup-specific cutoff (the heterogeneity of ROC curve) is underscored. We proposed a fuzzy set regression method to achieve such a purpose. The proposed method was illustrated with data on screening for osteoporosis with bone mineral density.

Does non-central nervous system tuberculosis increase the risk of ischemic stroke? A population-based propensity score-matched follow-up study.

BACKGROUND: Previous studies on the association between tuberculosis and the risk of developing ischemic stroke have generated inconsistent results. We therefore performed a population-based, propensity score-matched longitudinal follow-up study to investigate whether contracting non-central nervous system (CNS) tuberculosis leads to an increased risk of ischemic stroke. METHODS: We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 5804 persons with at least three ambulatory visits in 2001 with the principal diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The non-tuberculosis group consisted of 5804, propensity score-matched subjects without tuberculosis. The three-year ischemic stroke-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox proportional hazards regression was used to estimate the effect of tuberculosis on the occurrence of ischemic stroke. RESULTS: During three-year follow-up, 176 subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in the tuberculosis group was 0.92 compared to the non-tuberculosis group (95% confidence interval: 0.73-1.14, P = 0.4299). CONCLUSIONS: Non-CNS tuberculosis does not increase the risk of subsequent ischemic stroke.

Risk assessment of multistate progression of breast tumor with state-dependent genetic and environmental covariates.

Few studies have focused on the different roles risk factors play in the multistate temporal natural course of breast cancer. We proposed a three-state Markov regression model to predict the risk from free of breast cancer (FBC) to the preclinical screen-detectable phase (PCDP) and from the PCDP to the clinical phase (CP). We searched the initiators and promoters affecting onset and subsequent progression of breast tumor to build up a three-state temporal natural history model with state-dependent genetic and environmental covariates. This risk assessment model was applied to a 1 million Taiwanese women cohort. The proposed model was verified by external validation with another independent data set. We identified three kinds of initiators, including the BRCA gene, seven single nucleotides polymorphism, and breast density. ER, Ki-67, and HER-2 were found as promoters. Body mass index and age at first pregnancy both played a role. Among women carrying the BRCA gene, the 10-year predicted risk for the transition from FBC to CP was 25.83%, 20.31%, and 13.84% for the high-, intermediate-, and low-risk group, respectively. The corresponding figures were 1.55%, 1.22%, and 0.76% among noncarriers. The mean sojourn time of staying at the PCDP ranged from 0.82 years for the highest risk group to 6.21 years for the lowest group. The lack of statistical significance for external validation (x(4)2=5.30,p=0.26) revealed the adequacy of our proposed model. The three-state model with state-dependent covariates of initiators and promoters was proposed for achieving individually tailored screening and also for personalized clinical surveillance of early breast cancer.

Parkinson's disease is related to an increased risk of ischemic stroke-a population-based propensity score-matched follow-up study.

OBJECTIVE: The risk of stroke in patients with Parkinson's disease (PD) remains controversial. The purpose of this population-based propensity score-matched longitudinal follow-up study was to determine whether there is an increased risk of ischemic stroke after PD. METHODS: We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 2204 patients with at least two ambulatory visits with the principal diagnosis of PD in 2001 was enrolled in the PD group. The non- PD group consisted of 2204, propensity score-matched subjects without PD. The ischemic stroke-free survival rates of the two groups were estimated using the Kaplan-Meier method. Stratified Cox proportional hazard regression with patients matched on propensity score was used to estimate the effect of PD on the occurrence of ischemic stroke. RESULTS: During the three-year follow-up period, 328 subjects in the PD group and 156 subjects in the non-PD group developed ischemic stroke. The ischemic stroke-free survival rate of the PD group was significantly lower than that of the non-PD group (P<0.0001). The hazard ratio (HR) of stroke for the PD group was 2.37 (95% confidence interval [CI], 1.92 to 2.93, P<0.0001) compared to the non- PD group. CONCLUSIONS: This study shows a significantly increased risk of ischemic stroke in PD patients. Further studies are required to investigate the underlying mechanism.

Increased risk of hemorrhagic stroke in patients with migraine: a population-based cohort study.

OBJECTIVE: Previous studies on the association between migraine and the risk of developing hemorrhagic stroke (HS) have generated inconsistent results. The aim of the present population-based, age- and sex- matched follow-up study was to investigate whether migraine is associated with an increased risk of HS. METHOD: A total of 20925 persons with at least two ambulatory visits in 2001 with the principal diagnosis of migraine were enrolled in the migraine group. The non-migraine group consisted of 104625, age- and sex- matched, randomly sampled subjects without migraine. The two-year HS-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to estimate the effect of migraine on the occurrence of HS. RESULTS: During the 2 year follow-up, 113 subjects in the migraine group (0.54%) and 255 in the non-migraine group (0.24%) developed HS. The crude hazard ratio (HR) for developing HS in the migraine group was 2.22 compared to the non-migraine group (95% confidence interval [CI]: 1.78-2.77, p<0.0001) and the adjusted HR was 2.13 (95% CI: 1.71-2.67, p<0.0001) after controlling for demographic characteristics and comorbid medical disorders. CONCLUSIONS: This population-based age- and sex- matched cohort study shows that migraine was linked to an increased risk of HS.

Association of diabetes mellitus with the risk of developing adhesive capsulitis of the shoulder: a longitudinal population-based followup study.

OBJECTIVE: Although it has been suggested that diabetes mellitus (DM) is a risk factor for developing adhesive capsulitis of the shoulder (ACS), data on the temporal association between these 2 conditions are sparse. The purpose of this population-based age- and sex-matched cohort study was to investigate the risk of developing ACS in patients with newly diagnosed DM. METHODS: A total of 78,827 subjects with at least 2 ambulatory care visits with a principal diagnosis of DM in 2001 were recruited for the DM group. The non-DM group comprised 236,481 age- and sex-matched randomly sampled subjects without DM. The 3-year cumulative risk of ACS was calculated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to estimate the crude and adjusted hazard ratio (HR) of developing ACS. RESULTS: During a 3-year followup period, 946 subjects (1.20%) in the DM group and 2,254 subjects (0.95%) in the non-DM group developed ACS. The crude HR of developing ACS for the DM group compared to the non-DM group was 1.333 (95% confidence interval [95% CI] 1.236-1.439, P < 0.0001), whereas the adjusted HR was 1.321 (95% CI 1.224-1.425, P < 0.0001) after adjustment for age, sex, and dyslipidemia. CONCLUSION: This longitudinal population-based followup study showed that there is a significantly increased risk of developing ACS after developing DM.

A novel predictive score for hepatocellular carcinoma development in patients with chronic hepatitis C after sustained response to pegylated interferon and ribavirin combination therapy.

OBJECTIVES: Antiviral therapy can prevent the development of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients. However, HCC still develops in patients achieving sustained virological response (SVR). We proposed to evaluate the risk factors and derive a novel risk score for HCC (score(HCC)) by summation of products of clinical weights based on the regression coefficients in the final proportional hazards model. METHODS: From March 2002 to October 2009, we enrolled 871 patients with biopsy-proven CHC, who received combined pegylated interferon and ribavirin therapy and achieved SVR. RESULTS: Cox regression analysis showed that old age [hazard ratio (HR) 3.82, 95% CI 1.74-8.37, P = 0.001], high α-fetoprotein levels (HR 3.15, 95% CI 1.60-6.19, P = 0.001), low platelet counts (HR 2.81, 95% CI 1.22-6.44, P = 0.015) and high fibrotic stage (HR 3.95, 95% CI 1.46-10.70, P = 0.007) were independent risk factors. The cut-off level of risk scores was a derived value of 10 and was able to predict the HCC risk with 89.2% sensitivity and 69.5% specificity. The AUC value for the prediction was 0.848. The score(HCC) values were further categorized into three risk groups: low risk (score(HCC) ≤10), intermediate risk (score(HCC) 11-15) and high risk (score(HCC) ≥16). The proportion of HCC development increased from 1.37% (9/657) in the low-risk group to 9.14% (16/175) in the intermediate-risk group and 30.77% (12/39) in the high-risk group (P < 0.001). CONCLUSIONS: With the novel risk scores, we can estimate the chance of HCC development more exactly and practically. This approach can be used for HCC screening in CHC patients achieving SVR.

Geographic variation in the age- and gender-specific prevalence and incidence of epilepsy: analysis of Taiwanese National Health Insurance-based data.

PURPOSE: We studied geographic variation in age- and gender-specific prevalence and incidence of epilepsy in four different areas of Taiwan. METHODS: By using large-scale, National Health Insurance (NHI)-based data from 2000-2003 in Taiwan, we identified 131,287 patients diagnosed with epilepsy (ICD code 345) receiving at least of one of 11 antiepileptic drugs (AEDs). Information on age, gender, and location were also collected. The multivariable Poisson regression analysis was used to assess the heterogeneity of the morbidity of epilepsy in different regions. External data validation was also performed to assess the accuracy of capturing epilepsy cases through our NHI data set. KEY FINDINGS: The age-adjusted prevalence and incidence of epilepsy were 5.85 (per 1,000) between 2000 and 2003 and 97 (per 100,000 person-years) during the follow-up time from 2001 to 2003 in Taiwan. The sensitivity and specificity of ICD-9 coding for epilepsy in the NHI data set were 83.91% and 99.83%, respectively, resulting in a slight overestimation. Male patients had a higher probability of having epilepsy than did females. East Taiwan had significantly higher prevalence and incidence than did other areas. The age-specific incidence pattern in east Taiwan was atypical in that it revealed clustering in young and middle-aged groups. SIGNIFICANCE: Our study demonstrated geographic variation in epidemiologic patterns of epilepsy within Taiwan. The findings are informative and provide insight into the clinical management of epilepsy based on consideration of different target groups in different areas.

Increased risk of stroke after trigeminal neuralgia--a population-based follow-up study.

BACKGROUND: There are no reports on the risk of stroke after trigeminal neuralgia (TN). The aim of this population-based follow-up study was to investigate whether the occurrence of TN is associated with a higher risk of developing stroke. METHODS: A total of 1453 people with at least three ambulatory visits in 2001 with the principal diagnosis of TN were enrolled in the TN cohort. The non-TN cohort consisted of 5812 age- and sex-matched, randomly sampled subjects without TN. The 2-year stroke-free survival rate between the two groups was compared using the Kaplan-Meier method. The Cox proportional hazards regression model was used to estimate the hazard ratio of stroke after adjustment for demographic and clinical covariates. RESULTS: In the TN cohort, 73 patients developed stroke during follow-up, while in the non-TN cohort, 157 subjects suffered a stroke. The crude hazard ratio of stroke for the subjects with TN was 1.86 (95% CI, 1.41-2.45; p<0.0001). The adjusted hazard ratio was 1.76 (95% CI, 1.33-2.33; p<0.0001) after adjusting for demographic characteristics and comorbid medical disorders. CONCLUSION: This study showed a significantly increased risk of developing stroke after TN. Further studies are needed to investigate the underlying mechanism of this association.

The cost-utility analysis of 18-fluoro-2-deoxyglucose positron emission tomography in the diagnosis of recurrent nasopharyngeal carcinoma.

RATIONALE AND OBJECTIVES: 18-Fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) is effective but costly in the early detection of recurrence for nasopharyngeal carcinoma (NPC) in patients after treatment. In this study, we developed a decision tree model to analyze the cost utility of 18F-FDG PET in detecting loco-regional recurrences for NPC patients after therapy. MATERIALS AND METHODS: The analysis for cost utility is based on the decision-tree model for three different strategies: 1) magnetic resonance imaging (MRI)-only, 2) PET-only, and 3) MRI-PET (performing PET if MRI result is uncertain). Sensitivity analyses have been performed to examine changes in the cost ratio of PET/MRI and the probability of uncertain MRI. RESULTS: After inputting the data for utilities and life expectancies into the decision tree model, the quality-adjusted life expectancies turn out to be 16.16 quality-adjusted life-years (QALYs) for strategy 1, 16.70 QALYs for strategy 2, and 17.35 QALYs for strategy 3. The additional cost per additional QALYs for strategy 3 relative to strategy 1 is calculated to be US $462. Strategy 3 dominates over strategy 2 because strategy 3 costs less and yields more QALYs than strategy 2. If the cost ratio of PET/MRI is less than 1.85 or the probability of uncertain MRI is greater than 73%, then the PET-only strategy becomes more cost-effective than the MRI-PET strategy. CONCLUSION: Our analysis shows that the MRI-PET strategy is the most cost-effective for now. It is likely the PET-only strategy will become the most cost-effective for recurrent NPC in patients in the near future as the cost of PET has decreased in a faster rate than the cost of MRI.

Dynamic aspect of functional recovery after stroke using a multistate model.

OBJECTIVE: To estimate time to functional recovery and quantify the effects of significant prognostic factors affecting the dynamic change of 3-state functional outcome after stroke. DESIGN: Modeling of clinical predictions. SETTING: Referral center. PARTICIPANTS: One hundred eleven patients with first-time ischemic stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Serial Barthel Index scores at onset, 2 weeks, and 1, 2, 4, and 6 months poststroke. The severity of disability was classified into 3 functional states: poor functional state (PFS) for Barthel Index scores from 0 to 40, moderate functional state (MFS) for scores from 45 to 80, and good functional state (GFS) for scores greater than 80. A 3-state Markov regression model together with Bayesian acyclic graphic underpinning was used to estimate transition parameters and mean time to functional recovery between states and to predict the probability of functional recovery by using Gibbs sampling technique. RESULTS: The mean total recovery time was 3.1 months for patients with PFS at baseline and 1.3 months for patients with MFS at baseline. The mean recovery times to different functional states were also estimated. Age predominantly affected the probabilities of MFS to GFS transitions, younger patients had faster transition rates (rate ratio, 4.51; 95% confidence interval [CI], 2.72-7.40); but age had only borderline effects on PFS to MFS transitions. In contrast, infarct size exerted substantial effects on PFS to MFS transitions: small-size infarct correlated with a higher transition rate (rate ratio, 10.17; 95% CI, 5.25-20.13), whereas only a borderline effect on MFS to GFS transitions was found. The baseline functional state significantly affected the MFS to GFS transitions. CONCLUSIONS: By using a multistate model, overall and patient-specific mean time to functional recovery to different functional states can be estimated and the effect of clinical predictors on functional transitions can be precisely quantified to predict patient-specific probability of functional recovery.