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Anurekha Ramakrishnan, K. Michael Webb and Matthew C. Cowperthwaite


The authors comprehensively studied the recovery course and 1-year outcomes of early-crossover patients who were randomized to the nonoperative care arm of the Leiden–The Hague Spine Intervention Prognostic Study. The primary goal was to gain insight into the differences in the recovery patterns of early-crossover patients and those treated nonoperatively; secondary goals were to identify predictors of good 1-year outcomes, and to understand when and why patients were likely to cross over.


Individual EuroQol-5D scores were obtained at baseline and at 2, 4, 8, 12, 26, 38, and 52 weeks for 142 patients. Early-crossover patients were defined as those electing to undergo surgery during the first 12 weeks of treatment. Crossover and noncrossover groups were compared using Kruskal-Wallis, Wilcoxon-Mann-Whitney, and chi-square tests. Linear mixed-effects models were used to examine the growth trajectories of crossover and noncrossover groups. Recursive partitioning trees were used to model crossover events and the timing of crossover decisions. Multivariable logistic regression models were used to identify predictors of good 1-year outcomes.


Of the 142 patients randomized to receive prolonged nonoperative care, 136 were selected for the study. In this cohort, 43/136 (32%) opted for surgery, and 31/43 (72%) of crossover events occurred before the 12-week time point. Early-crossover patients had significantly greater functional impairment at Week 2 than noncrossover patients (p = 0.031), but experienced greater recovery by 26 weeks and better 1-year outcomes (p = 0.045). Patients who did not experience an improvement in their symptoms between 2 and 8 weeks were more likely to cross over (OR 3.5, 95% CI 1.2–10.1; p = 0.01). Recursive partitioning trees were able to identify crossover patients with 76% accuracy. Regression models suggested that better recovery at 26 weeks (p < 0.01) was predictive of good 1-year outcome; declining health status between Weeks 4 and 8 was negatively predictive of good outcome (p < 0.01).


This study is the first to comprehensively analyze the recovery and outcomes of crossover patients, and compare them to nonoperatively treated patients. The results suggest that patients who have a low EuroQol-5D score during the early weeks of treatment and who do not respond to nonoperative care during the first few weeks of treatment are most likely to cross over. Early-crossover patients experience a greater rate of recovery and more frequently have a good 1-year outcome when compared with nonoperatively treated patients. The current results motivate a broader investigation into the timing of surgery and the identification of patient populations that will be most benefited by early surgical treatment for lumbar disc herniation.

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Matthew C. Cowperthwaite, Deepankar Mohanty and Mark G. Burnett

As their power and utility increase, genome-wide association (GWA) studies are poised to become an important element of the neurosurgeon's toolkit for diagnosing and treating disease. In this paper, the authors review recent findings and discuss issues associated with gathering and analyzing GWA data for the study of neurological diseases and disorders, including those of neurosurgical importance. Their goal is to provide neurosurgeons and other clinicians with a better understanding of the practical and theoretical issues associated with this line of research. A modern GWA study involves testing hundreds of thousands of genetic markers across an entire genome, often in thousands of individuals, for any significant association with a particular disease. The number of markers assayed in a study presents several practical and theoretical issues that must be considered when planning the study. Genome-wide association studies show great promise in our understanding of the genes underlying common neurological diseases and disorders, as well as in leading to a new generation of genetic tests for clinicians.

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Matthew C. Cowperthwaite, Wilbert B. van den Hout and K. Michael Webb


The authors comprehensively studied the recovery of individual patients undergoing treatment for lumbar disc herniation. The primary goal was to gain insight into the variability of individual patient utility scores within a treatment cohort. The secondary goal was to determine how the rates and variability of patient recovery over time, represented by improvement in utility scores, affected long-term patient outcomes.


EuroQol Group–5 Dimension (EQ-5D) scores were obtained at baseline and at 2, 4, 8, 12, 26, 38, and 52 weeks for 93 patients treated under a prolonged conservative care protocol for lumbar disc herniation. Gaussian kernel densities were used to estimate the distribution of utility scores at each time point. Logistic regression and multistate Markov models were used to characterize individual patient improvement over time. Fisher exact tests were used to compare the distribution of EQ-5D domain scores.


The distribution of utility scores was bimodal at 1 year and effectively sorted patients into a “higher” utility group (EQ-5D = 1; 43% of cohort) and a “lower” utility group (EQ-5D ≤ 0.86; 57% of cohort). Fisher exact tests revealed that pain/discomfort, mobility, and usual activities significantly differed between the 2 utility groups (p ≪ 0.001). The utility groups emerged at 8 weeks and were stable for the remainder of the treatment period. Using utility scores from 8 weeks, regression models predicted 1-year outcomes with 62% accuracy.


This study is the first to comprehensively consider the utility recovery of individual patients within a treatment cohort for lumbar disc herniation. The results suggest that most utility is recovered during the early treatment period. Moreover, the findings suggest that initial improvement is critical to a patient's long-term outcome: patients who do not experience significant initial recovery appear unlikely to do so at a later time under the same treatment protocol.