Methods for comparing center‐specific survival outcomes using direct standardization

The evaluation of center‐specific outcomes is often through survival analysis methods. Such evaluations must account for differences in the distribution of patient characteristics across centers. In the context of censored event times, it is also important that the measure chosen to evaluate centers not be influenced by imbalances in the center‐specific censoring distributions. The practice of using center indicators in a hazard regression model is often invalid, inconvenient, or undesirable to carry out. We propose a semiparametric version of the standardized rate ratio (SRR) useful for the evaluation of centers with respect to a right‐censored event time. The SRR for center j can be interpreted as the ratio of the expected number of deaths in the total population (if the total population were in fact subject to the center j mortality hazard) to the observed number of events. The proposed measure is not affected by differences in center‐specific covariate or censoring distributions. Asymptotic properties of the proposed estimators are derived, with finite‐sample properties examined through simulation studies. The proposed methods are applied to national kidney transplant data. Copyright © 2014 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106887/1/sim6089.pd

Exact Solutions of the Klein-Gordon Equation in the Presence of a Dyon, Magnetic Flux and Scalar Potential in the Specetime of Gravitational Defects

In this paper we analyse the relativistic quantum motion of a charged spin-0 particle in the presence of a dyon, Aharonov-Bohm magnetic field and scalar potential, in the spacetimes produced by an idealized cosmic string and global monopole. In order to develop this analysis, we assume that the dyon and the Aharonov-Bohm magnetic field are superposed to both gravitational defects. Two distinct configurations for the scalar potential, $S(r)$, are considered: $i)$ the potential proportional to the inverse of the radial distance, i.e., $S\propto1/r$, and $ii)$ the potential proportional to this distance, i.e., $S\propto r$. For both cases the center of the potentials coincide with the dyon's position. In the case of the cosmic string the Aharonov-Bohm magnetic field is considered along the defect, and for the global monopole this magnetic field pierces the defect. The energy spectra are computed for both cases and explicitly shown their dependence on the electrostatic and scalar coupling constants. Also we analyse scattering states of the Klein-Gordon equations, and show how the phase shifts depend on the geometry of the spacetime and on the coupling constants parameter.Comment: To be published in CQG. Minor comments adde

Acceleration of hyperfractionated chemoradiation regimen for advanced head and neck cancer

Background. Our aim was to evaluate the acceleration of a hyperfractionated, concurrent chemoradiation regimen (HxCRT) for advanced head and neck squamous cell carcinoma (HNSCC). Methods. Patients with unresectable HNSCC were treated based on a previously published HxCRT regimen: 1.25 Gy twice daily to 70 Gy concurrent with cisplatin 12 mg/m 2 /day and5-fluorouracil 600 mg/m 2 /day for 5 days, weeks 1, 5. This regimen was accelerated in this series by shortening the treatment from 7 to 6 weeks by omitting the planned mid-treatment 1-week break. Results. Forty-six patients with T3-4/N3 disease were treated. The main acute toxicity was pharyngeal. Median weight change during therapy in patients with and without enteral feeding tubes was −3.8% and −7.9%, respectively ( p = .08). Fifteen percent had late grade III pharyngeal toxicity. Local/regional and distant failure rates were 28% and 17%, respectively; 52% are alive without evidence of disease. Conclusions. In nonresectable HNSCC, acceleration of the HxCRT regimen is feasible, requiring enteral feeding tubes during therapy in most patients. © 2006 Wiley Periodicals, Inc. Head Neck, 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55903/1/20495_ftp.pd

Markov model and markers of small cell lung cancer: assessing the influence of reversible serum NSE, CYFRA 21-1 and TPS levels on prognosis

High serum NSE and advanced tumour stage are well-known negative prognostic determinants of small cell lung cancer (SCLC) when observed at presentation. However, such variables are reversible disease indicators as they can change during the course of therapy. The relationship between risk of death and marker level and disease state during treatment of SCLC chemotherapy is not known. A total of 52 patients with SCLC were followed during cisplatin-based chemotherapy (the median number of tumour status and marker level assessments was 4). The time-homogeneous Markov model was used in order to analyse separately the prognostic significance of change in the state of the serum marker level (NSE, CYFRA 21-1, TPS) or the change in tumour status. In this model, transition rate intensities were analysed according to three different states: alive with low marker level (state 0), alive with high marker level (state 1) and dead (absorbing state). The model analysing NSE levels showed that the mean time to move out of state ‘high marker level’ was short (123 days). There was a 44% probability of the opposite reversible state ‘low marker level’ being reached, which demonstrated the reversible property of the state ‘high marker level’. The relative risk of death from this state ‘high marker level’ was about 2.24 times greater in comparison with that of state 0 ‘low marker level’ (Wald's test; P < 0.01). For patients in state ‘high marker level’ at time of sampling, the probability of death increased dramatically, a transition explaining the rapid decrease in the probability of remaining stationary at this state. However, a non-nil probability to change from state 1 ‘high marker level’ to the opposite transient level, state 0 ‘low marker level’, was observed suggesting that, however infrequently, patients in state 1 ‘high marker level’ might still return to state 0 ‘low marker level’. Almost similar conclusions can be drawn regarding the three-state model constructed using the tumour response status. For the two cytokeratin markers, the Markov model suggests the lack of a true reversible property of these variables as there was only a very weak probability of a patient returning to state ‘low marker level’ once having entered state ‘high marker level’. In conclusion, The Markov model suggests that the observation of an increase in serum NSE level or a lack of response of the disease at any time during follow-up (according to the homogeneous assumption) was strongly associated with a worse prognosis but that the reversion to a low mortality risk state remains possible. © 1999 Cancer Research Campaig

Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation

AbstractObjectivesWe studied the outcomes of pediatric patients diagnosed with dilated cardiomyopathy (DCM) and their relation to epidemiologic and echocardiographic variables at the time of presentation.BackgroundThe outcome of pediatric DCM patients ranges from recovery to a 50% to 60% chance of death within five years of diagnosis. The impact of heart transplantation and other emerging therapies on the outcomes of pediatric DCM patients is uncertain.MethodsWe performed a retrospective study of the outcomes in 91 pediatric patients diagnosed with DCM from 1990 to 1999. Routine therapy included use of digoxin, diuretics, angiotensin-converting enzyme inhibitors, and heart transplantation.ResultsAt the time of last follow-up, 11 patients (12%) had died without transplantation; 20 (22%) underwent transplantation; 27 (30%) had persistent cardiomyopathy; and 33 (36%) had recovery of left ventricular systolic function. Overall actuarial one-year survival was 90%, and five-year survival was 83%. However, actuarial freedom from “heart death” (death or transplantation) was only 70% at one year and 58% at five years. Multivariate analysis found age <1 year (hazard ratio 7.1), age >12 years (hazard ratio 4.5), and female gender (hazard ratio 3.0) to be significantly associated with a greater risk of death or transplantation and a higher left ventricular shortening fraction at presentation (hazard ratio 0.92), with a slightly decreased risk of death or transplantation.ConclusionsPediatric DCM patients continue to have multiple outcomes, with recovery of left ventricular systolic function occurring most frequently. Utilization of heart transplantation has led to improved survival after the diagnosis of pediatric DCM

Assessment of possible impact of a health promotion program in Korea from health risk trends in a longitudinally observed cohort

BACKGROUND: Longitudinally observed cohort data can be utilized to assess the potential for health promotion and healthcare planning by comparing the estimated risk factor trends of non-intervened with that of intervened. The paper seeks (1) to estimate a natural transition (patterns of movement between states) of health risk state from a Korean cohort data using a Markov model, (2) to derive an effective and necessary health promotion strategy for the population, and (3) to project a possible impact of an intervention program on health status. METHODS: The observed transition of health risk states in a Korean employee cohort was utilized to estimate the natural flow of aggregated health risk states from eight health risk measures using Markov chain models. In addition, a reinforced transition was simulated, given that a health promotion program was implemented for the cohort, to project a possible impact on improvement of health status. An intervened risk transition was obtained based on age, gender, and baseline risk state, adjusted to match with the Korean cohort, from a simulated random sample of a US employee population, where a health intervention was in place. RESULTS: The estimated natural flow (non-intervened), following Markov chain order 2, showed a decrease in low risk state by 3.1 percentage points in the Korean population while the simulated reinforced transition (intervened) projected an increase in low risk state by 7.5 percentage points. Estimated transitions of risk states demonstrated the necessity of not only the risk reduction but also low risk maintenance. CONCLUSIONS: The frame work of Markov chain efficiently estimated the trend, and captured the tendency in the natural flow. Given only a minimally intense health promotion program, potential risk reduction and low risk maintenance was projected

Outcomes of High-Dose-Rate Interstitial Brachytherapy in the Treatment of Locally Advanced Cervical Cancer: Long-term Results

PURPOSE: The purpose of this study was to determine locoregional control (LRC), disease-free survival (DFS), and toxicity of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the treatment of locally advanced cervical cancer. METHODS AND MATERIALS: Between March 1996 and May 2009, 116 patients with cervical cancer were treated. Of these, 106 (91%) patients had advanced disease (International Federation of Gynecology and Obstetrics stage IIB-IVA). Ten patients had stage IB, 48 had stage II, 51 had stage III, and 7 had stage IVA disease. All patients were treated with a combination of external beam radiation therapy (EBRT) to the pelvis (5040 cGy) and 2 applications of HDR-ISBT to a dose of 3600 cGy to the implanted volume. Sixty-one percent of patients also received interstitial hyperthermia, and 94 (81%) patients received chemotherapy. RESULTS: Clinical LRC was achieved in 99 (85.3%) patients. Three-year DFS rates were 59%, 67%, 71%, and 57% for patients with stage IB, II, III, and IVA disease, respectively. The 5-year DFS and overall survival rates for the entire group were 60% and 44%, respectively. Acute and late toxicities were within acceptable limits. CONCLUSIONS: Locally advanced cervical cancer patients for whom intracavitary BT is unsuitable can achieve excellent LRC and OS with a combination of EBRT and HDR-ISBT