Group sequential monitoring of years of life saved with paired censored survival data

This research develops non-parametric methodology for sequential monitoring of paired time-to-event data when comparing years of life saved, or years where any unpleasant outcome is delayed, is of interest. The recommended family of test statistics uses integrated differences in survival estimates that are available during the study period, where adjustments are made for dependence in the survival and censoring outcomes under comparison. In the context of paired censored survival data, the joint asymptotic closed form distribution of these sequentially monitored test statistics is developed and shown to have a dependent increments structure. Simulations verifying nice operating characteristics of the proposed monitoring methods also reveal consequences of ignoring an underlying paired data structure in terms of size and power properties. A motivating example is also presented via the Early Treatment Diabetic Retinopathy Study, which did not have methods available for sequentially monitoring paired censored survival data at the time. Copyright © 2002 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34859/1/990_ftp.pd

Nonparametric Rank-Based Methods for Group Sequential Monitoring of Paired Censored Survival Data

This research gives methods for nonparametric sequential monitoring of paired censored survival data in the two-sample problem using paired weighted log-rank statistics with adjustments for dependence in survival and censoring outcomes. The joint asymptotic closed-form distribution of these sequentially monitored statistics has a dependent increments structure. Simulations validating operating characteristics of the proposed methods highlight power and size consequences of ignoring even mildly correlated data. A motivating example is presented via the Early Treatment Diabetic Retinopathy Study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65768/1/j.0006-341X.2000.0984.x.pd

Using Weighted Kaplan-Meier Statistics in Nonparametric Comparisons of Paired Censored Survival Outcomes

This research introduces methods for nonparametric testing of weighted integrated survival differences in the context of paired censored survival designs. The current work extends work done by Pepe and Fleming (1989, Biometrics 45 , 497–507), which considered similar test statistics directed toward independent treatment group comparisons. An asymptotic closed-form distribution of the proposed family of tests is presented, along with variance estimates constructed under null and alternative hypotheses using nonparametric maximum likelihood estimates of the closed-form quantities. The described method allows for additional information from individuals with no corresponding matched pair member to be incorporated into the test statistic in sampling scenarios where singletons are not prone to selection bias. Simulations presented over a range of potential dependence in the paired censored survival data demonstrate substantial power gains associated with taking into account the dependence structure. Consequences of ignoring the paired nature of the data include overly conservative tests in terms of power and size. In fact, simulation results using tests for independent samples in the presence of positive correlation consistently undershot both size and power targets that would have been attained in the absence of correlation. This additional worrisome effect on operating characteristics highlights the need for accounting for dependence in this popular family of tests.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66383/1/j.0006-341X.2001.00361.x.pd

Visual fields in patients who have undergone vitrectomy for complications of diabetic retinopathy. A prospective study

BACKROUND: To determine the extent of visual field loss in patients who had required a pars plana vitrectomy secondary to complications of proliferative diabetic retinopathy. METHODS: Patients that had undergone a vitrectomy on at least one eye for treatment of either vitreous haemorrhage or tractional retinal detachment were selected for study. ETDRS acuity and Humphrey binocular Esterman visual field testing were performed and compared to the minimum standards for safe driving as defined by the Royal College of Ophthalmologists in 1999. In addition to this Goldman kinetic visual fields using a III4e and V4e stimulus size and central 24-2 threshold test with the SITA-fast strategy were performed on the vitrectomised eye. RESULTS: 20 patients (n = 20) were recruited. Mean visual acuity in the eye being tested was 0.20 (Snellen 6/9.5). Results from the Humphrey field analyzer showed a mean number of abnormal stimulus locations of 71.2% (p < 0.005). 70% of patients had sufficient binocular acuity to drive and of these 71.4% were shown not to have a minimum visual field for safe driving on binocular Esterman field analysis. CONCLUSION: Vitrectomy potentially allows retention/restoration of good visual acuity in patients with complications of proliferative diabetic retinopathy. However patients may be suffering from unrecognized visual impairment consequent upon extensive visual field loss which in over two thirds of patients may be sufficiently severe to preclude safe driving

Analgesic Effects of Tramadol During Panretinal Photocoagulation

PURPOSE: To evaluate the effectiveness of tramadol for the reduction of pain in panretinal photocoagulation (PRP). METHODS: A double-masked randomized controlled study was performed. Fifty-eight eyes in 29 patients with proliferative diabetic retinopathy were enrolled. The eyes of the patients were randomized into two groups. Group A received an empty capsule. Group B received an oral intake of 100 mg tramadol. The capsule used in Group A had the same appearance as that used in Group B. Pain during PRP was assessed using a visual analog scale. Vital signs, including blood pressure and heart rate, were measured. RESULTS: The mean pain scores for groups A and B were 4.80+/-2.10 and 3.83+/-1.82 (p=0.09). There were no significant differences in the mean pain scores between the two groups. More patients in group A complained of greater pain than moderate intensity (visual analogue scale=4). Systemic blood pressure increased significantly in group A after laser treatment. However, there were no significant differences in the diastolic blood pressure changes between the two groups. We found no statistical correlation in the heart rate changes. CONCLUSIONS: We failed to prove that tramadol is effective for pain relief because of the small sample size. However, tramadol was effective for the relief of more severe pain. It was also found to stabilize vital sign changes, such as systolic blood pressure during PRP

Risk of diabetic retinopathy at first screen in children at 12 and 13 years of age

AIMS: \ud \ud To investigate the relationships between age at diagnosis of diabetes, age at diabetic eye screening and severity of diabetic retinopathy at first and subsequent screenings in children aged 12 or 13 years.\ud \ud METHODS: \ud \ud Data were extracted from four English screening programmes and from the Scottish, Welsh and Northern Irish programmes on all children with diabetes invited for their first and subsequent screening episodes from the age of 12 years. Retinopathy levels at first and subsequent screens, time from diagnosis of diabetes to first screening and age at diagnosis in years were calculated.\ud \ud RESULTS: \ud \ud Data were available for 2125 children with diabetes screened for the first time at age 12 or 13 years. In those diagnosed with diabetes at 2 years of age or less, the proportion with retinopathy in one or both eyes was 20% and 11%, respectively, decreasing to 8% and 2% in those diagnosed between 2 and 12 years (P < 0.0001). Only three children (aged 8, 10 and 11 years at diagnosis of diabetes) had images graded with referable retinopathy and, of these, two had non-referable diabetic retinopathy at all subsequent screenings. Of 1703 children with subsequent images, 25 were graded with referable diabetic retinopathy over a mean follow-up of 3.1 years, an incidence rate of 4.7 (95% confidence interval, 3.1-7.0) per 1000 per year.\ud \ud CONCLUSIONS: \ud \ud In this large cohort of children, the low prevalence and incidence rates of referable diabetic retinopathy suggest that screening earlier than age 12 is not necessary