A SIMULATION STUDY OF THE SIZE AND POWER OF SOME TWO-SAMPLE TESTS FOR UNEQUALLY CENSORED SURVIVAL DATA (RANK TESTS, LOGRANK, PROPORTIONAL HAZARDS, WILCOXON TESTS, EXPONENTIAL DISTRIBUTION)

Sizes and power of selected two-sample tests of the equality of survival distributions are compared by simulation for small samples from unequally, randomly-censored exponential distributions. The tests investigated include parametric tests (F, Score, Likelihood, Asymptotic), logrank tests (Mantel, Peto-Peto), and Wilcoxon-Type tests (Gehan, Prentice). Equal sized samples, n = 18, 16, 32 with 1000 (size) and 500 (power) simulation trials, are compared for 16 combinations of the censoring proportions 0%, 20%, 40%, and 60%. For n = 8 and 16, the Asymptotic, Peto-Peto, and Wilcoxon tests perform at nominal 5% size expectations, but the F, Score and Mantel tests exceeded 5% size confidence limits for 1/3 of the censoring combinations. For n = 32, all tests showed proper size, with the Peto-Peto test most conservative in the presence of unequal censoring. Powers of all tests are compared for exponential hazard ratios of 1.4 and 2.0. There is little difference in power characteristics of the tests within the classes of tests considered. The Mantel test showed 90% to 95% power efficiency relative to parametric tests. Wilcoxon-type tests have the lowest relative power but are robust to differential censoring patterns. A modified Peto-Peto test shows power comparable to the Mantel test. For n = 32, a specific Weibull-exponential comparison of crossing survival curves suggests that the relative powers of logrank and Wilcoxon-type tests are dependent on the scale parameter of the Weibull distribution. Wilcoxon-type tests appear more powerful than logrank tests in the case of late-crossing and less powerful for early-crossing survival curves. Guidelines for the appropriate selection of two-sample tests are given. ^

A hybrid method in combining treatment effects from matched and unmatched studies

In the biomedical studies, the general data structures have been the matched (paired) and unmatched designs. Recently, many researchers are interested in Meta-Analysis to obtain a better understanding from several clinical data of a medical treatment. The hybrid design, which is combined two data structures, may create the fundamental question for statistical methods and the challenges for statistical inferences. The applied methods are depending on the underlying distribution. If the outcomes are normally distributed, we would use the classic paired and two independent sample T-tests on the matched and unmatched cases. If not, we can apply Wilcoxon signed rank and rank sum test on each case. ^ To assess an overall treatment effect on a hybrid design, we can apply the inverse variance weight method used in Meta-Analysis. On the nonparametric case, we can use a test statistic which is combined on two Wilcoxon test statistics. However, these two test statistics are not in same scale. We propose the Hybrid Test Statistic based on the Hodges-Lehmann estimates of the treatment effects, which are medians in the same scale.^ To compare the proposed method, we use the classic meta-analysis T-test statistic on the combined the estimates of the treatment effects from two T-test statistics. Theoretically, the efficiency of two unbiased estimators of a parameter is the ratio of their variances. With the concept of Asymptotic Relative Efficiency (ARE) developed by Pitman, we show ARE of the hybrid test statistic relative to classic meta-analysis T-test statistic using the Hodges-Lemann estimators associated with two test statistics.^ From several simulation studies, we calculate the empirical type I error rate and power of the test statistics. The proposed statistic would provide effective tool to evaluate and understand the treatment effect in various public health studies as well as clinical trials.^

A process evaluation of a health literacy intervention targeting pediatric providers' communication skills at the Texas Children's Health Plan

Background. Health literacy is an important determinant for quality health care, and affects communication between patients and physicians. Poor communication may result in negative effects in health. Improved communication between patients and physicians could positively affect health outcomes. Communication skills are teachable.^ Objectives. (1) to evaluate the process involved in the design and implementation of a health literacy intervention targeting pediatric providers’ communication skills at the Texas Children’s Health Plan in Houston, Texas; and (2) to describe lessons learned from this process that may be used in future attempts to address the issue of health literacy and health communication. ^ Design/methods. The process evaluation of the implementation of a health literacy strategy at the Texas Children’s Health Plan (TCHP) consisted of a critical analysis of all documents and minutes from meetings of the team of investigators. It also involved a secondary analysis of data collected between December 2006 and June 2007. Descriptive statistics, paired t-test and Wilcoxon-signed-rank test were employed in analyzing the data. This information was complemented with a limited review of existing literature on communication skills training programs. ^ Results. The design of the educational intervention followed recommendations from experts in the field of health literacy. The delivery of the intervention was possible and benefited from existing resources and logistics within the TCHP. Very few targeted providers participated in two offerings of the workshop (6.6% and 1.7% respectively). After the educational intervention, providers showed increased knowledge of health literacy facts and its effects in health (p=0.001); increased awareness of the low health literacy problem (p=0.003); increased expectations for change in practice (p=0.002), and intent to use health literacy strategies for communication immediately following the intervention (p=0.001). Low participation indicated the need for further investigation of barriers to, and means for successful implementation of programs aimed to improving health communication. ^ Conclusions. A short, focused intervention utilizing health literacy strategies for communication appeared effective in increasing knowledge and intentions for change in a small group of pediatric providers. ^

The impact of a child's unexpected hospitalization upon Taiwanese parents' situational anxiety

Background. The parents of a sick child likely experience situational anxiety due to their young child being unexpectedly hospitalized. The emotional upheaval may be great enough that their anxiety inhibits them in providing positive support to their hospitalized child. Because anxiety affects psychological distress as well as behavioral distress, identifying parental distress helps parents improving their coping mechanisms. ^ Purpose. The study compared situational anxiety levels between Taiwanese fathers and mothers and focused on differences between parental anxiety levels at the beginning of the child's unplanned hospitalization and at time of discharge. The study also identified factors related to the parents' distress and use of coping mechanisms. ^ Methods. A descriptive, comparative research design was used to determine the difference between the anxiety levels of 62 Taiwanese father-mother dyads during the situational crisis of their child's unexpected hospitalization. The Mandarin version (M) of Visual Analog Scale (VAS-M), State-Trait Anxiety Inventory (STAI-M), and the Index of Parent Participation/Hospitalized Child (IPP/HC-M) were used to differentiate maternal and paternal anxiety levels and identify factors related to the parents' distress. Questionnaires were completed by parents within 24-36 hours of the child's hospital admission and within 24 hours prior to discharge. A paired t-test, two sample t-test, and linear mixed regression model were used to test and support the study hypothesis. ^ Results. The findings reveal that the mothers' anxiety levels did not significantly differ from the fathers' anxiety level when their child had a sudden admission to the hospital. In particular, parental state anxiety levels did not decrease during the child's hospital stay and subsequent discharge. Moreover, anxiety levels did not differ between parents regardless of whether the child's disease was acute or chronic. The most effective factor related to parental situational anxiety was parental perception of the severity of the child's illness. ^ Conclusions. Parental anxiety was found to be significantly related to changes in their perception of the severity of their child's illness. However, the study was not able to illustrate how parental involvement in the child's hospital care was related to parental perception of the severity of their child's illness. Future studies, using a qualitative approach to gamer more information as to what variables influence parental anxiety during a situational crisis, may provide a richer database from which to modify key variables as well as the instruments used to improve the quality of the data obtained. ^

Assessing time-by-covariate interactions in Cox proportional hazards regression models using cubic spline functions

This dissertation develops and explores the methodology for the use of cubic spline functions in assessing time-by-covariate interactions in Cox proportional hazards regression models. These interactions indicate violations of the proportional hazards assumption of the Cox model. Use of cubic spline functions allows for the investigation of the shape of a possible covariate time-dependence without having to specify a particular functional form. Cubic spline functions yield both a graphical method and a formal test for the proportional hazards assumption as well as a test of the nonlinearity of the time-by-covariate interaction. Five existing methods for assessing violations of the proportional hazards assumption are reviewed and applied along with cubic splines to three well known two-sample datasets. An additional dataset with three covariates is used to explore the use of cubic spline functions in a more general setting. ^

Cataract surgery in cancer patients and its impact on quality of life as measured by the National Eye Institute Visual Functioning Questionnaire - 25 (NEI-VFQ-25)

Purpose. The measurement of quality of life has become an important topic in healthcare and in the allocation of limited healthcare resources. Improving the quality of life (QOL) in cancer patients is paramount. Cataract removal and lens implantation appears to improve patient well-being of cancer patients, though a formal measurement has never been published in the US literature. In this current study, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), a validated vision quality of life metric, was used to study the change in vision-related quality of life in cancer patients who underwent cataract extraction with intraocular lens implantation. ^ Methods. Under an IRB approved protocol, cancer patients who underwent cataract surgery with intraocular lens implantation (by a single surgeon) from December 2008 to March 2011, and who had completed a pre- and postoperative NEI-VFQ-25 were retrospectively reviewed. Post-operative data was collected at their routine 4-6 week post-op visit. Patients' demographics, cancer history, their pre and postoperative ocular examinations, visual acuities, and NEI-VFQ-25 with twelve components were included in the evaluation. The responses were evaluated using the Student t test, Spearman correlation and Wilcoxon signed rank test. ^ Results. 63 cases of cataract surgery (from 54 patients) from the MD Anderson Cancer Center were included in the study. Cancer patients had a significant improvement in the visual acuity (P<0.0001) postoperatively, along with a significant increase in vision-related quality of life (P<0.0001). Patients also had a statistically significant improvement in ten of the twelve subcategories which are addressed in the NEI-VFQ-25. ^ Conclusions. In our study, cataract extraction and intraocular implantation showed a significant impact on the vision-related quality of life in cancer patients. Although this study includes a small sample size, it serves as a positive pilot study to evaluate and quantify the impact of a surgical intervention on QOL in cancer patients and may help to design a larger study to measure vision related QOL per dollar spent for health care cost in cancer patients.^

An assessment of differences in pediatric dental services provided for a Medicaid population when compared to a federally subsidized (military) clinic

Reimbursement for dental services performed for children receiving Medicaid is reimbursed per service while dental treatment for military dependents provided at a military installation is neither directly reimbursable to those providing the care nor billed to those receiving the care. The purpose of this study was to compare pediatric dental services provided for a Medicaid population to a federally subsidized military facility to compare treatment choices and subsequent costs of care. It was hypothesized that differences in dental procedures for Medicaid and military dependent children would exist based upon treatment philosophy and payment method. A total of 240 records were reviewed for this study, consisting of 120 Medicaid patients at the University of Texas Health Science Center at San Antonio (UTHSCSA) and 120 military dependents at Wilford Hall Medical Center (WHMC), Lackland Air Force Base, San Antonio. Demographic data and treatment information were abstracted for children receiving dental treatment under general anesthesia between 2002 and 2006. Data was analyzed using the Wilcoxon rank sum test, Kruskal-Wallis test, and Fisher's exact test. The Medicaid recipients treated at UTHSCSA were younger than patients at WHMC (40.2 vs. 49.8 months, p<.001). The university also treated significantly more Hispanic children than WHMC (78.3% vs. 30.0%, p<.001). Children at UTHSCSA had a mean of 9.5 decayed teeth and were treated with 2.3 composite fillings, 0 amalgam fillings, 5.6 stainless steel crowns, 1.1 pulp therapies, 1.6 extractions, and 1.0 sealant. Children at WHMC had a mean of 8.7 decayed teeth and were treated with 1.4 composite fillings, 0.9 amalgam fillings, 5.6 stainless steel crowns, 1.7 pulp therapies, 0.9 extractions, and 2.1 sealants. The means of decayed teeth, total fillings, and stainless steel crowns were not statistically different. UTHSCSA provided more composite fillings (p<.001), fewer amalgam fillings (p<.001), fewer pulp therapies (p <.001), more extractions (p=.01), and fewer sealants (p<.001) when compared to WHMC. Age and gender did not effect decay rates, but those of Hispanic ethnicity did experience more decay than non-Hispanics (9.5 vs. 8.6, p=.02). Based upon Texas Medicaid reimbursement rates from 2006, the cost for dental treatment at both sites was approximately $650 per child. The results of this study do not support the hypothesis that Medicaid providers provide less conservative therapies, which would be more costly, care when compared to a military treatment center. ^

HIV-associated malignancies among children attending the Baylor Clinic in Kampala, Uganda

Introduction: HIV-associated malignancies such as Kaposi’s sarcoma and Non-Hodgkin’s lymphoma occur in children and usually lead to significant morbidity and mortality. No studies have been done to establish prevalence and outcome of these malignancies in children in a hospital setting in Uganda. ^ Research question: What proportion of children attending the Baylor-Uganda COE present with HIV-associated malignancies and what are the characteristics and outcome of these malignancies? The objective was to determine the prevalence, associated factors and outcome of HIV-associated malignancies among children attending the Baylor-Uganda Clinic in Kampala, Uganda. Study Design: This was a retrospective case series involving records review of patients who presented to the Baylor-Clinic between January 2004 and December 2008. Study Setting: The Baylor-Uganda Clinic, where I worked as a physician before coming to Houston, is a well funded, well staffed; Pediatric HIV clinic located in Mulago Hospital, Kampala, Uganda and is affiliated to Makerere University Medical School. Study Participants: Medical charts of patients aged 6 weeks to 18 years who enrolled for care at the clinic during the years 2004 to 2008 were retrieved for data abstraction. Selection Criteria: Study participants had to be patients of Baylor-Uganda seen during the study period; they had to be aged 6 weeks to 18 years; and had to be HIV positive. Patients with incomplete data or whose malignancies were not confirmed by histology were excluded. Study Variables: Data on patient’s age, sex, diagnosis, type of malignancy, anatomic location of the malignancy; pathology report, baseline laboratory results and outcome of treatment, were abstracted. Data Analysis: Cross tabulation to determine associations between variables using Pearson’s chi square at 95% level of significance was done. Proportions of malignancies among different groups were determined. In addition, Kaplan Meier survival analysis and comparison of survival distributions using the log-rank test was done. Change in CD4 percentages from baseline was assessed with the Wilcoxon signed rank test. Results: The proportion of children with malignancies during the study period was found to be 1.65%. Only 2 malignancies: Kaposi’s sarcoma and Non-Hodgkin’s lymphoma were found. 90% of the malignancies were Kaposi’s sarcoma. Lymph node involvement in children with Kaposi’s sarcoma was common, but the worst prognosis was seen with visceral involvement. Deaths during follow-up were seen in the first few weeks to months. Upon starting treatment the CD4 cell percentage increased significantly from a baseline median of 6% to 14% at 6 months and 15.8% at 12 months of follow-up.^

Childhood cancer survivor satisfaction with characteristics of clinical care

This study investigated the characteristics of a clinic that affect how satisfied survivors of childhood cancer are with their medical care. Questionnaire and interview data from the Passport for Care: Texas Implementation project collected between January 2011 to April 2012 were analyzed. Eleven clinics in Texas participated. Questionnaire respondents were childhood cancer survivor patients who had been off therapy for at least 2 years, or their parents. Interview respondents were clinical providers or research staff at the participating clinics. The outcomes evaluated were answers to a single question on satisfaction with care and a composite Percent Satisfaction Score created from seven other questionnaire items that were correlated (Spearman Rho >0.3) with the question on satisfaction. The following characteristics were also evaluated: sex, age, race, education, and type of cancer. The following clinic indicators were evaluated: type of clinic (general vs. dedicated cancer survivor clinics), number of providers, number of survivors, ratio of survivors/providers, distribution of handouts, distribution of treatment summaries, and use of Children's Oncology Group (COG) guidelines. ^ The only demographic characteristic that affected satisfaction was race. A Kruskal-Wallis test showed a statistically significant difference (Chi-square 6.129, 2 d.f., p = 0.0467). To analyze this further, Wilcoxon Rank Sum test of pairings of the three groups were performed. A Bonferroni correction for multiple testing was applied, with p = 0.017 indicating significance at alpha = 0.05. There was no significant difference between the White and Hispanic groups or between the Hispanic and "Other" groups. For the White and "Other" groups there was a significant difference for the satisfaction item (p = 0.0123) but not for the Percent Satisfaction Score (p = 0.0289). These results suggest that race may influence satisfaction and should be evaluated further in future studies. ^ None of the clinic indicators affected the Percent Satisfaction Score. Going to a clinic that distributed patient information handouts (Wilcoxon Rank Sum p = 0.048) and going to a clinic with >=100 survivors (Wilcoxon Rank Sum p = 0.021) were associated with increased satisfaction. The population of childhood cancer survivors is a growing group of individuals with special health needs. In the future survivors will likely seek medical care in a variety of clinical settings, so it is important to investigate features to improve patient satisfaction with clinical care.^