Likelihood devices in spatial statistics

One of the main themes of this thesis is the application to spatial data of modern semi- and nonparametric methods. Another, closely related theme is maximum likelihood estimation from spatial data. Maximum likelihood estimation is not common practice in spatial statistics. The method of moments and minimum contrast methods are traditionally more often applied. The thesis is organized around three problems. 1. Laslett's line segment problem. We observe the intersection of a random set and a collection of scattered linesegments of random length. We find a non-parametric maximum likelihood estimator for the length distribution of the line segments. We prove consistency of our estimator. 2. Estimation of the chord length distribution. This problem is a variation of Laslett's problem. We estimate the distribution of the length of a typical chord of a random set. The chord length distibution is closely related to the more familiar linear contact distribution. 3. Estimation for the Boolean model of discs. Here we observe the union of randomly scattered discs. We present a method to approximate the maximum likelihood estimator (MLE) of the mean number of disc-centers per unit area. Direct computation of the MLE is impossible because occlusion prevents us from observing the presence of a disc's center when the disc itself is completely covered by other discs. Our way around this problem involves an algorithm to sample from random point processes conditioned to have a given property. The thesis is selfcontained in that theory and tools are described in an introductory chapter. In addition, this chapter features some new theory on the consistency of the maximum likelihood estimator and a modification of the stochastic version of the EM algorithm

The significance filter, the winner's curse and the need to shrink

The "significance filter" refers to focusing exclusively on statistically significant results. Since frequentist properties such as unbiasedness and coverage are valid only before the data have been observed, there are no guarantees if we condition on significance. In fact, the significance filter leads to overestimation of the magnitude of the parameter, which has been called the "winner's curse." It can also lead to undercoverage of the confidence interval. Moreover, these problems become more severe if the power is low. These issues clearly deserve our attention. They have been studied mostly through empirical observation and simulation, while there are relatively few mathematical results. Here we study them both from the frequentist and the Bayesian perspective. We prove that the relative bias of the magnitude is a decreasing function of the power and that the usual confidence interval undercovers when the power is less than 50%. We conclude that it is important to apply the appropriate amount of shrinkage to counter the winner's curse.Development and application of statistical models for medical scientific researc

SPES/SCOPA and MDS-UPDRS: Formulas for converting scores of two motor scales in Parkinson’s disease

AbstractBackgroundMotor impairment in Parkinson’s disease (PD) can be evaluated with the Short Parkinson’s Evaluation Scale/Scales for Outcomes in Parkinson’s disease (SPES/SCOPA) and the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The aim of this study was to determine equation models for the conversion of scores from one scale to the other.Methods148 PD patients were evaluated with the SPES/SCOPA-motor and the MDS-UPDRS motor examination. Linear regression was used to develop equation models.ResultsScores on both scales were highly correlated (r = 0.88). Linear regression revealed the following equation models (explained variance: 78%):1.MDS-UPDRS motor examination score = 11.8 + 2.4 ∗ SPES/SCOPA-motor score2.SPES/SCOPA-motor score = −0.5 + 0.3 ∗ MDS-UPDRS motor examination score.ConclusionWith the equation models identified in this study, scores from SPES/SCOPA-motor can be converted to scores from MDS-UPDRS motor examination and vice versa

Simultaneous confidence intervals for ranks with application to ranking institutions

When a ranking of institutions such as medical centers or universities is based on a numerical measure of performance provided with a standard error, confidence intervals (CIs) should be calculated to assess the uncertainty of these ranks. We present a novel method based on Tukey's honest significant difference test to construct simultaneous CIs for the true ranks. When all the true performances are equal, the probability of coverage of our method attains the nominal level. In case the true performance measures have no exact ties, our method is conservative. For this situation, we propose a rescaling method to the nominal level that results in shorter CIs while keeping control of the simultaneous coverage. We also show that a similar rescaling can be applied to correct a recently proposed Monte-Carlo based method, which is anticonservative. After rescaling, the two methods perform very similarly. However, the rescaling of the Monte-Carlo based method is computationally much more demanding and becomes infeasible when the number of institutions is larger than 30-50. We discuss another recently proposed method similar to ours based on simultaneous CIs for the true performance. We show that our method provides uniformly shorter CIs for the same confidence level. We illustrate the superiority of our new methods with a data analysis for travel time to work in the United States and on rankings of 64 hospitals in the Netherlands.Development and application of statistical models for medical scientific researc

Increased blood pressure and body mass index as potential modifiable factors in the progression of myocardial dysfunction in duchenne muscular dystrophy

Background: Duchenne muscular dystrophy (DMD) is characterized by progressive cardiomyopathy. Left ventricular (LV) function may worsen by factors increasing LV afterload such as hypertension and obesity.Objective: To identify potential modifiable risk factors for progression of cardiomyopathy in Duchenne muscular dystrophy (DMD).Methods: We retrospectively analysed systolic blood pressures (SBP) and body-mass indexes (BMI) from 273 visits of 65 DMD patients aged 4-18 years between 2003 and 2016, divided in 14 age groups. Values were normalized using Z-scores (Z-SBP and Z-BMI). A linear mixed model was used to analyse correlations between Z-SBP and BMI, steroid use, age, ambulatory status and cardiac medication (CM) use. To study the relationship between SBP and BMI and myocardial deformation prior to the onset of clinical cardiomyopathy, LV deformation, defined by global longitudinal strain (GLS), was quantified in a subset of 36 patients <11 years. Multiple linear regression was used to study the relation between GLS and clinical parameters.Results: Median follow-up was 5 years. SBP was significantly elevated in all age groups under 14 years (p <= 0.04) and 15-16 years (p = 0.033) and correlated positively with BMI (p = 0.001) and negatively with CM use over time (p = 0.018). Z-BMI followed a bell-shaped distribution and plotted approximately one standard deviation above the mean in patients between 7 and 15 years. In the subset of younger patients, reduced GLS was associated with higher BMI ((beta = 0.348, p = 0.004).Conclusions: SBP and BMI may be potentially modifiable factors to retard deterioration of LV function in DMD.Developmen

Temporal Relationship of Asystole to Onset of Transient Loss of Consciousness in Tilt-Induced Reflex Syncope

ObjectivesThe purpose of this study was to investigate the relationship between the onset of asystole and transient loss of consciousness (TLOC) in tilt-induced reflex syncope and estimate how often asystole was the principal cause of TLOC.BackgroundThe presence of asystole in vasovagal syncope (VVS) may prompt physicians to consider pacemaker therapy for syncope prevention, but the benefit of pacing is limited in VVS.MethodsWe evaluated electrocardiography, electroencephalography, blood pressure, and clinical findings during tilt-table tests. Inclusion required TLOC (video), electroencephalographic slowing, accelerating blood pressure decrease, and an RR interval ≥3 s. We excluded cases with nitroglycerin provocation. Asystole after onset of TLOC (group A) or within 3 seconds before TLOC (group B) was unlikely to cause TLOC, but an earlier start of asystole (group C) could be the cause of TLOC.ResultsIn one-third of 35 cases (groups A [n = 9] and B [n = 3]), asystole was unlikely to be the primary cause of TLOC. The median of the mean arterial pressure at the onset of asystole was higher when asystole occurred early (45.5 mm Hg, group C) than when it occurred late (32.0 mm Hg, groups A and B), which suggests that vasodepression was not prominent at the start of asystole in early asystole, further suggesting that early asystole was the prime mechanism of syncope.ConclusionsIn one-third of cases of tilt-induced asystolic reflex syncope, asystole occurred too late to have been the primary cause of TLOC. Reliance on electrocardiography data only is likely to overestimate the importance of asystole.</div

Gamification to engage clinicians in registering data: A randomized trial

Action Contro

Identification of risk factors in minimally invasive surgery: a prospective multicenter study

Development and application of statistical models for medical scientific researc

Behavioural intervention in medication overuse headache: a concealed double-blind randomized controlled trial

Background and purpose Medication overuse headache is a prevalent disorder, with a strong biobehavioural component. Hence, behavioural interventions might effectuate reduction of the overused medication. We assessed in a double-blind manner the efficacy of a behavioural intervention during medication withdrawal therapy. Methods In this concealed, double-blind, randomized controlled trial in medication overuse headache, conducted at the Leiden University Medical Centre, we compared the effect of maximal versus minimal behavioural intervention by a headache nurse during withdrawal therapy. Maximal intervention consisted of an intensive contact schedule, comprising education, motivational interviewing, and value-based activity planning during 12 weeks of withdrawal therapy. Minimal intervention consisted of a short contact only. Patients were unaware of the existence of these treatment arms, as the trial was concealed in another trial investigating botulinum toxin A. Endpoints were successful withdrawal and monthly days of acute medication use after the withdrawal period. Results We enrolled 179 patients (90 maximal, 89 minimal intervention). At Week 12, most patients achieved withdrawal in both groups (82/90 [93%] maximal intervention vs. 75/89 [86%] minimal intervention, odds ratio = 2.44, 95% confidence interval [CI] = 0.83-7.23, p = 0.107). At Week 24, patients in the maximal intervention group had fewer medication days (mean difference = -2.23, 95% CI = -3.76 to -0.70, p = 0.005). This difference receded over time. Change in monthly migraine days did not differ between groups (-6.75 vs. -6.22). Conclusions This trial suggests modest benefit of behavioural intervention by a headache nurse during withdrawal therapy for medication overuse headache, to reduce acute medication use during and shortly after intervention, but extension seems warranted for a prolonged effectParoxysmal Cerebral Disorder