Measuring value in cancer-related health care: A case study in head and neck cancer

In the current climate of escalating health care costs, defining value and accurately measuring it are two critical issues affecting not only the future of cancer care in particular but also the future of health care in general. Specifically, measuring and improving value in cancer-related health care are critical for continued advancements in research, management, and overall delivery of care. However, in oncology, most of this research has focused on value as it relates to insurance industry and payment reform, with little attention paid to value as the output of clinical interventions that encompass integrated clinical teams focusing on the entire cycle of care and measuring objective outcomes that are most relevant to patients. ^ In this study, patient-centered value was defined as health outcomes achieved per dollar spent, and calculated using objective functional outcomes and total care costs. The analytic sample comprised patients diagnosed with three common head and neck cancers—cancer of the larynx, oral cavity, and oropharynx—who were treated in an integrated tertiary care center over an approximately 10-year period. The results of this study provide initial empirical data that can be used to assess and ultimately to help improve the quality and value of head and neck cancer care, and more importantly they can be used by patients and clinicians to make better-informed decisions about care, particularly what therapeutic services and outcomes matter the most to patients.^

An empirical evaluation of the Random Forests classifier models for variable selection in a large-scale lung cancer case-control study

Random Forests™ is reported to be one of the most accurate classification algorithms in complex data analysis. It shows excellent performance even when most predictors are noisy and the number of variables is much larger than the number of observations. In this thesis Random Forests was applied to a large-scale lung cancer case-control study. A novel way of automatically selecting prognostic factors was proposed. Also, synthetic positive control was used to validate Random Forests method. Throughout this study we showed that Random Forests can deal with large number of weak input variables without overfitting. It can account for non-additive interactions between these input variables. Random Forests can also be used for variable selection without being adversely affected by collinearities. ^ Random Forests can deal with the large-scale data sets without rigorous data preprocessing. It has robust variable importance ranking measure. Proposed is a novel variable selection method in context of Random Forests that uses the data noise level as the cut-off value to determine the subset of the important predictors. This new approach enhanced the ability of the Random Forests algorithm to automatically identify important predictors for complex data. The cut-off value can also be adjusted based on the results of the synthetic positive control experiments. ^ When the data set had high variables to observations ratio, Random Forests complemented the established logistic regression. This study suggested that Random Forests is recommended for such high dimensionality data. One can use Random Forests to select the important variables and then use logistic regression or Random Forests itself to estimate the effect size of the predictors and to classify new observations. ^ We also found that the mean decrease of accuracy is a more reliable variable ranking measurement than mean decrease of Gini. ^

The diagnostic value of a 12-lead electrocardiogram in patients with cardiac tamponade due to a malignant pericardial effusion

Background. Cardiac tamponade can occur when a large amount of fluid, gas, singly or in combination, accumulating within the pericardium, compresses the heart causing circulatory compromise. Although previous investigators have found the 12-lead ECG to have a poor predictive value in diagnosing cardiac tamponade, very few studies have evaluated it as a follow up tool for ruling in or ruling out tamponade in patients with previously diagnosed malignant pericardial effusions. ^ Methods. 127 patients with malignant pericardial effusions at the MD Anderson Cancer Center were included in this retrospective study. While 83 of these patients had a cardiac tamponade diagnosed by echocardiographic criteria (Gold standard), 44 did not. We computed the sensitivity (Se), specificity (Sp), positive (PPV) and negative predictive values (NPV) for individual and combinations of ECG abnormalities. Individual ECG abnormalities were also entered singly into a univariate logistic regression model to predict tamponade. ^ Results. For patients with effusions of all sizes, electrical alternans had a Se, Sp, PPV and NPV of 22.61%, 97.61%, 95% and 39.25% respectively. These parameters for low voltage complexes were 55.95%, 74.44%, 81.03%, 46.37% respectively. The presence of all three ECG abnormalities had a Se = 8.33%, Sp = 100%, PPV = 100% and NPV = 35.83% while the presence of at least one of the three ECG abnormalities had a Se = 89.28%, Sp = 46.51%, PPV = 76.53%, NPV = 68.96%. For patients with effusions of all sizes electrical alternans had an OR of 12.28 (1.58–95.17, p = 0.016), while the presence of at least one ECG abnormality had an OR of 7.25 (2.9–18.1, p = 0.000) in predicting tamponade. ^ Conclusions. Although individual ECG abnormalities had low sensitivities, specificities, NPVs and PPVs with the exception of electrical alternans, the presence of at least one of the three ECG abnormalities had a high sensitivity in diagnosing cardiac tamponade. This could point to its potential use as a screening test with a correspondingly high NPV to rule out a diagnosis of tamponade in patients with malignant pericardial effusions. This could save expensive echocardiographic assessments in patients with previously diagnosed pericardial effusions. ^

NEW TOOLS FOR MONITORING GAMMA CAMERA UNIFORMITY

Detector uniformity is a fundamental performance characteristic of all modern gamma camera systems, and ensuring a stable, uniform detector response is critical for maintaining clinical images that are free of artifact. For these reasons, the assessment of detector uniformity is one of the most common activities associated with a successful clinical quality assurance program in gamma camera imaging. The evaluation of this parameter, however, is often unclear because it is highly dependent upon acquisition conditions, reviewer expertise, and the application of somewhat arbitrary limits that do not characterize the spatial location of the non-uniformities. Furthermore, as the goal of any robust quality control program is the determination of significant deviations from standard or baseline conditions, clinicians and vendors often neglect the temporal nature of detector degradation (1). This thesis describes the development and testing of new methods for monitoring detector uniformity. These techniques provide more quantitative, sensitive, and specific feedback to the reviewer so that he or she may be better equipped to identify performance degradation prior to its manifestation in clinical images. The methods exploit the temporal nature of detector degradation and spatially segment distinct regions-of-non-uniformity using multi-resolution decomposition. These techniques were tested on synthetic phantom data using different degradation functions, as well as on experimentally acquired time series floods with induced, progressively worsening defects present within the field-of-view. The sensitivity of conventional, global figures-of-merit for detecting changes in uniformity was evaluated and compared to these new image-space techniques. The image-space algorithms provide a reproducible means of detecting regions-of-non-uniformity prior to any single flood image’s having a NEMA uniformity value in excess of 5%. The sensitivity of these image-space algorithms was found to depend on the size and magnitude of the non-uniformities, as well as on the nature of the cause of the non-uniform region. A trend analysis of the conventional figures-of-merit demonstrated their sensitivity to shifts in detector uniformity. The image-space algorithms are computationally efficient. Therefore, the image-space algorithms should be used concomitantly with the trending of the global figures-of-merit in order to provide the reviewer with a richer assessment of gamma camera detector uniformity characteristics.

Congenital diaphragmatic hernia in the preterm infant.

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains a significant cause of death in newborns. With advances in neonatal critical care and ventilation strategies, survival in the term infant now exceeds 80% in some centers. Although prematurity is a significant risk factor for morbidity and mortality in most neonatal diseases, its associated risk with infants with CDH has been described poorly. We sought to determine the impact of prematurity on survival using data from the Congenital Diaphragmatic Hernia Registry (CDHR). METHODS: Prospectively collected data from live-born infants with CDH were analyzed from the CDHR from January 1995 to July 2009. Preterm infants were defined as <37 weeks estimated gestational age at birth. Univariate and multivariate logistic regression analysis were>performed. RESULTS: During the study period, 5,069 infants with CDH were entered in the registry. Of the 5,022 infants with gestational age data, there were 3,895 term infants (77.6%) and 1,127 preterm infants (22.4%). Overall survival was 68.7%. A higher percentage of term infants were treated with extracorporeal membrane oxygenation (ECMO) (33% term vs 25.6% preterm). Preterm infants had a greater percentage of chromosomal abnormalities (4% term vs 8.1% preterm) and major cardiac anomalies (6.1% term vs 11.8% preterm). Also, a significantly higher percentage of term infants had repair of the hernia (86.3% term vs 69.4% preterm). Survival for infants that underwent repair was high in both groups (84.6% term vs 77.2% preterm). Survival decreased with decreasing gestational age (73.1% term vs 53.5% preterm). The odds ratio (OR) for death among preterm infants adjusted for patch repair, ECMO, chromosomal abnormalities, and major cardiac anomalies was OR 1.68 (95% confidence interval [CI], 1.34-2.11). CONCLUSION: Although outcomes for preterm infants are clearly worse than in the term infant, more than 50% of preterm infants still survived. Preterm infants with CDH remain a high-risk group. Although ECMO may be of limited value in the extremely premature infant with CDH, most preterm infants that live to undergo repair will survive. Prematurity should not be an independent factor in the treatment strategies of infants with CDH.

The location of majority and minority populations with respect to commercial treatment, storage, and disposal facilities in Texas

There is a growing interest in the location of Treatment, Storage, and Disposal (TSDF) sites in relation to minority communities. A number of studies have been completed, and the results of these studies have been varied. Some of the studies have shown a strong positive correlation between the location of TSDF sites and minority populations, while a few have shown no significance in that relationship. The major difference between these studies has been in the areal unit used.^ This study compared the minority populations of Texas census tracts and ZIP codes containing a TSDF using the associated county as the comparison population. The hypothesis of this study was that there was no difference between using census tracts and ZIP codes to analyze the relationship of minority populations and TSDF's. The census data used was from 1990, and the initial list of TSDF sites was supplied by the Texas Natural Resource Conservation Commission. The TSDF site locations were checked using graphical information systems (GIS) programs, in order to increase the accuracy of the identity of exposed ZIP codes and census tracts. The minority populations of the exposed areal units were compared using proportional differences, crosstables, maps, and logistic regression. The dependent variable used was the exposure status of the areal units under study, including counties, census tracts, and ZIP codes. The independent variables used included minority group proportion and grouping of the proportions, educational status, household income, and home value.^ In all cases, education was significant or near significant at the.05 level. Education rather than minority proportion was therefore the most significant predictor of the exposure status of a census tract or ZIP code. ^

Endogenous nitric oxide regulates p53 signaling and DNA damage-induced apoptosis in melanoma cells

Nitric oxide is involved in a multitude of processes including regulation of vascular tone, neurotransmission, immunity, and cancer. Evidence suggests that nitric oxide exhibits anti-apoptotic activity in melanoma cells. Our laboratory showed that tumor expression of inducible nitric oxide synthase correlated strongly with poor survival in stage III and IV melanoma patients, suggesting an antagonistic role for nitric oxide in melanoma response to therapy. Therefore, the hypothesis that endogenously produced nitric oxide antagonizes chemotherapy-induced apoptosis was formed. Using cisplatin as a model for DNA damage in melanoma cell lines, the capacity of nitric oxide to regulate cell growth and apoptotic responses to cisplatin treatment was examined. The depletion of endogenously generated nitric oxide resulted in changes in cell cycle regulation and enhanced cisplatin-induced apoptosis in melanoma cells. Since nitric oxide was shown to be involved in the regulation of p53 stability, conformation and DNA binding activity, whether signaling through wild-type p53 in melanoma cells is regulated by nitric oxide was tested. Cisplatin-induced p53 accumulation and p21Waf1/Cip1/Sdi1 expression in nitric oxide-depleted melanoma cells were found to be strongly suppressed. When p53 binding to the p21Waf1/Cip1/Sdi1 promoter was examined, it was found that nitric oxide depletion significantly reduced the cisplatin-induced formation of p53-DNA complexes. These results suggest that nitric oxide is required for activation of wild-type p53 after DNA damage in melanoma cells. Finally, whether signaling through p53 controls melanoma response to DNA damage was examined. Transfection of a plasmid containing a dominant negative form of mutated p53 inhibited p21 Waf1/Cip1/Sdi1 expression and concomitantly enhanced apoptosis after cisplatin treatment. These data suggest that the induction of wild-type p53 protects melanoma cells against DNA damage via the up-regulation of p21 Waf1/Cip1/Sdi1. Together, these data strongly support the model that endogenous nitric oxide is required for p53 activation and p21Waf1/Cip1/Sdi1 expression after DNA damage, which can enhance melanoma resistance to therapy. Thus, in context of melanoma cells with wild-type p53 , low levels of endogenous constitutively-produced nitric oxide appear to facilitate the activation of p53 in response to DNA damage, thereby allowing for cell cycle arrest via p21Waf1/Cip1/Sdi1 induction, adequate DNA repair, and ultimately enhanced resistance to apoptosis. ^