All Publications

  • A Predictive-Modeling Based Screening Tool for Prolonged Opioid Use after Surgical Management of Low Back and Lower Extremity Pain. The spine journal : official journal of the North American Spine Society Zhang, Y., Fatemi, P., Medress, Z., Azad, T. D., Veeravagu, A., Desai, A., Ratliff, J. K. 2020


    Outpatient postoperative pain management in spine patients, specifically involving the use of opioids, demonstrates significant variability.Using preoperative risk factors and 30-day postoperative opioid prescribing patterns, we developed models for predicting long-term opioid use in patients after elective spine surgery.This retrospective cohort study utilizes inpatient, outpatient, and pharmaceutical data from MarketScan databases (Truven Health).In all, 19,317 patients who were newly diagnosed with low back or lower extremity pain (LBP or LEP) between 2008 and 2015 and underwent thoracic or lumbar surgery within one year after diagnosis were enrolled. Some patients initiated opioids after diagnosis but all patients were opioid-naïve prior to the diagnosis.Long-term opioid use was defined as filling ≥180 days of opioids within one year after surgery.Using demographic variables, medical and psychiatric comorbidities, preoperative opioid use, and 30-day postoperative opioid use, we generated seven models on 80% of the dataset and tested the models on the remaining 20%. We used three regression-based models (full logistic regression, stepwise logistic regression, least absolute shrinkage and selection operator [LASSO]), support vector machine, two tree-based models (random forest, stochastic gradient boosting), and time-varying convolutional neural network. Area under the curve (AUC), Brier index, sensitivity, and calibration curves were used to assess the discrimination and calibration of the models.We identified 903 (4.6%) of patients who met criteria for long-term opioid use. The regression-based models demonstrated the highest AUC, ranging from 0.835 to 0.847, and relatively high sensitivities, predicting between 74.9-76.5% of the long-term opioid use patients in the test dataset. The three strongest positive predictors of long-term opioid use were high preoperative opioid use (OR 2.70; 95% CI 2.27-3.22), number of days with active opioid prescription between postoperative days 15-30 (OR 1.10; 95% CI 1.07-1.12), and number of dosage increases between postoperative day 15-30 (OR 1.71, 95% CI 1.41-2.08). The strongest negative predictors were number of dosage decreases in the 30-day postoperative period.We evaluated several predictive models for postoperative long-term opioid use in a large cohort of patients with LBP or LEP who underwent surgery. A regression-based model with high sensitivity and AUC is provided online to screen patients for high risk of long-term opioid use based on preoperative risk factors and opioid prescription patterns in the first 30 days after surgery. It is hoped that this work will improve identification of patients at high risk of prolonged opioid use and enable early intervention and counseling.

    View details for DOI 10.1016/j.spinee.2020.05.098

    View details for PubMedID 32445803

  • Lumboperitoneal and Ventriculoperitoneal Shunting for Idiopathic Intracranial Hypertension Demonstrate Comparable Failure and Complication Rates. Neurosurgery Azad, T. D., Zhang, Y., Varshneya, K., Veeravagu, A., Ratliff, J. K., Li, G. 2019


    Idiopathic intracranial hypertension results in increased intracranial pressure leading to headache and visual loss. This disease frequently requires surgical intervention through lumboperitoneal (LP) or ventriculoperitoneal (VP) shunting.To compare postoperative outcomes between LP and VP shunts, including failure and complication rates.A retrospective analysis was conducted using a national administrative database (MarketScan) to identify idiopathic intracranial hypertension (IIH) patients who underwent LP or VP shunting from 2007 to 2014. Multivariate logistic and Cox regressions were performed to compare rates of shunt failure and time to shunt failure between LP and VP shunts while controlling for demographics and comorbidities.The analytic cohort included 1082 IIH patients, 347 of whom underwent LP shunt placement at index hospitalization and 735 of whom underwent VP shunt placement. Rates of shunt failure were similar among patients with LP and VP shunt (34.6% vs 31.7%; P = .382). Among patients who experienced shunt failure, the mean number of shunt failures was 2.1 ± 1.6 and was similar between LP and VP cohorts. Ninety-day readmission rates, complication rates, and costs did not differ significantly between LP and VP shunts. Patients who experienced more than two shunt failures tended to have an earlier time to first shunt failure (hazard ratio 1.41; 95% confidence interval 1.08-1.85; P = .013).These findings suggest that LP and VP shunts may have comparable rates of shunt failure and complication. Regardless of shunt type, earlier time to first shunt failure may be associated with multiple shunt failures.

    View details for PubMedID 30937428

  • Predictive Modeling of Long-Term Opioid and Benzodiazepine Use after Intradural Tumor Resection. The spine journal : official journal of the North American Spine Society Jin, M. C., Ho, A. L., Feng, A. Y., Zhang, Y., Staartjes, V. E., Stienen, M. N., Han, S. S., Veeravagu, A., Ratliff, J. K., Desai, A. M. 2020


    INTRODUCTION: Despite increased awareness of the ongoing opioid epidemic, opioid and benzodiazepine use remain high after spine surgery. In particular, long-term co-prescription of opioids and benzodiazepines have been linked to high risk of overdose-associated death. Tumor patients represent a unique subset of spine surgery patients and few studies have attempted to develop predictive models to anticipate long-term opioid and benzodiazepine use after spinal tumor resection.METHODS: The IBM Watson Health MarketScan Database and Medicare Supplement were assessed to identify admissions for intradural tumor resection between 2007 and 2015. Adult patients were required to have at least 6-months of continuous pre-admission baseline data and 12-months of continuous post-discharge follow-up. Primary outcomes were long-term opioid and benzodiazepine use, defined as at least 6 prescriptions within 12 months. Secondary outcomes were durations of opioid and benzodiazepine prescribing. Logistic regression models, with and without regularization, were trained on an 80% training sample and validated on the withheld 20%.RESULTS: A total of 1,942 patients were identified. The majority of tumors were extramedullary (74.8%) and benign (62.5%). A minority of patients received arthrodesis (9.2%) and most patients were discharged to home (79.1%). Factors associated with post-discharge opioid use duration include tumor malignancy (vs benign, B=19.8 prescribed-days/year, 95% CI 1.1 to 38.5) and intramedullary compartment (vs extramedullary, B=18.1 prescribed-days/year, 95% CI 3.3 to 32.9). Pre- and peri-operative use of prescribed NSAIDs and gabapentin/pregabalin were associated with shorter and longer duration opioid use, respectively. History of opioid and history of benzodiazepine use were both associated with increased post-discharge opioid and benzodiazepine use. Intramedullary location was associated with longer duration post-discharge benzodiazepine use (B=10.3 prescribed-days/year, 95% CI 1.5 to 19.1). Among assessed models, elastic net regularization demonstrated best predictive performance in the withheld validation cohort when assessing both long-term opioid use (AUC=0.748) and long-term benzodiazepine use (AUC=0.704). Applying our model to the validation set, patients scored as low-risk demonstrated a 4.8% and 2.4% risk of long-term opioid and benzodiazepine use, respectively, compared to 35.2% and 11.1% of high-risk patients.CONCLUSIONS: We developed and validated a parsimonious, predictive model to anticipate long-term opioid and benzodiazepine use early after intradural tumor resection, providing physicians opportunities to consider alternative pain management strategies.

    View details for DOI 10.1016/j.spinee.2020.10.010

    View details for PubMedID 33065272

  • Opioid Use in Adults with Low Back or Lower Extremity Pain who Undergo Spine Surgical Treatment within One Year of Diagnosis. Spine Fatemi, P., Zhang, Y., Ho, A., Lama, R., Jin, M., Veeravagu, A., Desai, A., Ratliff, J. K. 2020


    Retrospective longitudinal cohort.We investigated opioid prescribing patterns amongst adults in the United States diagnosed with low back or lower extremity pain (LBP/LEP) who underwent spine surgery.Opioid-based treatment of LBP/LEP and postsurgical pain have separately been associated with chronic opioid use, but a combined and large-scale cohort study is missing.This study utilizes commercial inpatient, outpatient, and pharmaceutical insurance claims. Between 2008 and 2015, patients without prior prescription opioids with a new diagnosis of LBP/LEP who underwent surgery within one year after diagnosis were enrolled. Opioid prescribing patterns after LBP/LEP diagnosis and after surgery were evaluated. All patients had one-year postoperative follow-up. Low and high frequency (≥6 refills in 12 months) opioid prescription groups were identified.25,506 patients without prior prescription opioids were diagnosed with LBP/LEP and underwent surgery within one year of diagnosis. After LBP/LEP diagnosis, 18,219 (71.4%) were prescribed opioids while 7,287 (28.6%) were not. After surgery, 2,952 (11.6%) were prescribed opioids with high frequency and 22,554 (88.4%) with low frequency. Among patients prescribed opioids prior to surgery, those with high frequency prescriptions were more likely to continue this pattern postoperatively than those with low frequency prescriptions preoperatively (OR:2.15, 95% CI:1.97-2.34). For those prescribed opioids preoperatively, average daily morphine milligram equivalent (MME) decreased after surgery (by 2.62 in decompression alone cohort and 0.25 in arthrodesis cohort, p < 0.001). Postoperative low-frequency patients were more likely than high-frequency patients to discontinue opioids one-year after surgery (OR:3.78, 95% CI:3.59-3.99). Postoperative high-frequency patients incurred higher cost than low-frequency patients. Postoperative high-frequency prescribing varied widely across states (4.3%-20%).A stepwise association exists between opioid use after LEP or LBP diagnosis and frequency and duration of opioid prescriptions after surgery. Simultaneously, the strength of prescriptions as measured by MME decreased following surgery.3.

    View details for DOI 10.1097/BRS.0000000000003663

    View details for PubMedID 32833930

  • Costs and Complications Associated with Resection of Supratentorial Tumors with and without the Operative Microscope in the United States. World neurosurgery Zhang, Y., Zhang, M., Lin, M., Gephart, M. H., Veeravagu, A., Ratliff, J. K., Li, G. 2020


    The operative microscope, a commonly used tool in neurosurgery, is critical in many supratentorial tumor cases. However, use of operating microscope for supratentorial tumor varies by surgeon.To assess complication rates, readmissions, and costs associated with operative microscope use in supratentorial resections.A retrospective analysis was conducted using a national administrative database to identify patients with glioma or brain metastases who underwent supratentorial resection between 2007 and 2016. Univariate and multivariate analyses were used to assess 30-day complications, readmissions and costs between patients who underwent resection with and without use of microscope.The cohort included 12058 glioma patients and 5433 metastasis patients. Rates of microscope use varied by state from 19.0% to 68.6%. Microscope use was associated with $5228.9 in additional costs of index hospitalization among glioma patients (p < 0.001), and $2824.0 among metastasis patients (p < 0.001). Rates of intraoperative cerebral edema were lower among the microscope cohort than among the non-microscope cohort (p < 0.027). Microscope use was associated with a slight reduction in 30-day rates of neurological complications (14.7% vs. 16.7%, p = 0.048), specifically in nonspecific cerebrovascular complications. There were no differences in rates of other complications, readmissions, or 30-day postoperative costs.Use of operative microscope for supratentorial resections varies by state and is associated with higher cost of surgery. Microscope use may be associated with lower rates of intraoperative cerebral edema and some cerebrovascular complications, but is not associated with significant differences in other complications, readmissions, or 30-day costs.

    View details for DOI 10.1016/j.wneu.2020.03.021

    View details for PubMedID 32171932

  • Brain Iron Assessment after Ferumoxytol-enhanced MRI in Children and Young Adults with Arteriovenous Malformations: A Case-Control Study. Radiology Iv, M., Ng, N. N., Nair, S., Zhang, Y., Lavezo, J., Cheshier, S. H., Holdsworth, S. J., Moseley, M. E., Rosenberg, J., Grant, G. A., Yeom, K. W. 2020: 200378


    Background Iron oxide nanoparticles are an alternative contrast agent for MRI. Gadolinium deposition has raised safety concerns, but it is unknown whether ferumoxytol administration also deposits in the brain. Purpose To investigate whether there are signal intensity changes in the brain at multiecho gradient imaging following ferumoxytol exposure in children and young adults. Materials and Methods This retrospective case-control study included children and young adults, matched for age and sex, with brain arteriovenous malformations who received at least one dose of ferumoxytol from January 2014 to January 2018. In participants who underwent at least two brain MRI examinations (subgroup), the first and last available examinations were analyzed. Regions of interests were placed around deep gray structures on quantitative susceptibility mapping and R2* images. Mean susceptibility and R2* values of regions of interests were recorded. Measurements were assessed by linear regression analyses: a between-group comparison of ferumoxytol-exposed and unexposed participants and a within-group (subgroup) comparison before and after exposure. Results Seventeen participants (mean age ± standard deviation, 13 years ± 5; nine male) were in the ferumoxytol-exposed (case) group, 21 (mean age, 14 years ± 5; 11 male) were in the control group, and nine (mean age, 12 years ± 6; four male) were in the subgroup. The mean number of ferumoxytol administrations was 2 ± 1 (range, one to four). Mean susceptibility (in parts per million [ppm]) and R2* (in inverse seconds [sec-1]) values of the dentate (case participants: 0.06 ppm ± 0.04 and 23.87 sec-1 ± 4.13; control participants: 0.02 ppm ± 0.03 and 21.7 sec-1 ± 5.26), substantia nigrae (case participants: 0.08 ppm ± 0.06 and 27.46 sec-1 ± 5.58; control participants: 0.04 ppm ± 0.05 and 24.96 sec-1 ± 5.3), globus pallidi (case participants: 0.14 ppm ± 0.05 and 30.75 sec-1 ± 5.14; control participants: 0.08 ppm ± 0.07 and 28.82 sec-1 ± 6.62), putamina (case participants: 0.03 ppm ± 0.02 and 20.63 sec-1 ± 2.44; control participants: 0.02 ppm ± 0.02 and 19.65 sec-1 ± 3.6), caudate (case participants: -0.1 ppm ± 0.04 and 18.21 sec-1 ± 3.1; control participants: -0.06 ppm ± 0.05 and 18.83 sec-1 ± 3.32), and thalami (case participants: 0 ppm ± 0.03 and 16.49 sec-1 ± 3.6; control participants: 0.02 ppm ± 0.02 and 18.38 sec-1 ± 2.09) did not differ between groups (susceptibility, P = .21; R2*, P = .24). For the subgroup, the mean interval between the first and last ferumoxytol administration was 14 months ± 8 (range, 1-25 months). Mean susceptibility and R2* values of the dentate (first MRI: 0.06 ppm ± 0.05 and 25.78 sec-1 ± 5.9; last MRI: 0.06 ppm ± 0.02 and 25.55 sec-1 ± 4.71), substantia nigrae (first MRI: 0.06 ppm ± 0.06 and 28.26 sec-1 ± 9.56; last MRI: 0.07 ppm ± 0.06 and 25.65 sec-1 ± 6.37), globus pallidi (first MRI: 0.13 ppm ± 0.07 and 27.53 sec-1 ± 8.88; last MRI: 0.14 ppm ± 0.06 and 29.78 sec-1 ± 6.54), putamina (first MRI: 0.03 ppm ± 0.03 and 19.78 sec-1 ± 3.51; last MRI: 0.03 ppm ± 0.02 and 19.73 sec-1 ± 3.01), caudate (first MRI: -0.09 ppm ± 0.05 and 21.38 sec-1 ± 4.72; last MRI: -0.1 ppm ± 0.05 and 18.75 sec-1 ± 2.68), and thalami (first MRI: 0.01 ppm ± 0.02 and 17.65 sec-1 ± 5.16; last MRI: 0 ppm ± 0.02 and 15.32 sec-1 ± 2.49) did not differ between the first and last MRI examinations (susceptibility, P = .95; R2*, P = .54). Conclusion No overall significant differences were found in susceptibility and R2* values of deep gray structures to suggest retained iron in the brain between ferumoxytol-exposed and unexposed children and young adults with arteriovenous malformations and in those exposed to ferumoxytol over time. © RSNA, 2020.

    View details for DOI 10.1148/radiol.2020200378

    View details for PubMedID 32930651

  • Patterns of Opioid and Benzodiazepine Use in Opioid-Naive Patients with Newly Diagnosed Low Back and Lower Extremity Pain. Journal of general internal medicine Azad, T. D., Zhang, Y., Stienen, M. N., Vail, D., Bentley, J. P., Ho, A. L., Fatemi, P., Herrick, D., Kim, L. H., Feng, A., Varshneya, K., Jin, M., Veeravagu, A., Bhattacharya, J., Desai, M., Lembke, A., Ratliff, J. K. 2019


    BACKGROUND: The morbidity and mortality associated with opioid and benzodiazepine co-prescription is a pressing national concern. Little is known about patterns of opioid and benzodiazepine use in patients with acute low back pain or lower extremity pain.OBJECTIVE: To characterize patterns of opioid and benzodiazepine prescribing among opioid-naive, newly diagnosed low back pain (LBP) or lower extremity pain (LEP) patients and to investigate the relationship between benzodiazepine prescribing and long-term opioid use.DESIGN/SETTING: We performed a retrospective analysis of a commercial database containing claims for more than 75 million enrollees in the USA.PARTICIPANTS: Participants were adult patients newly diagnosed with LBP or LEP between 2008 and 2015 who did not have a red flag diagnosis, had not received an opioid prescription in the 6months prior to diagnosis, and had 12months of continuous enrollment after diagnosis.MAIN OUTCOMES AND MEASURES: Among patients receiving at least one opioid prescription within 12months of diagnosis, we defined discrete patterns of benzodiazepine prescribing-continued use, new use, stopped use, and never use. We tested the association of these prescription patterns with long-term opioid use, defined as six or more fills within 12months.RESULTS: We identified 2,497,653 opioid-naive patients with newly diagnosed LBP or LEP. Between 2008 and 2015, 31.9% and 11.5% of these patients received opioid and benzodiazepine prescriptions, respectively, within 12months of diagnosis. Rates of opioid prescription decreased from 34.8% in 2008 to 27.0% in 2015 (P<0.001); however, prescribing of benzodiazepines only decreased from 11.6% in 2008 to 10.8% in 2015. Patients with continued or new benzodiazepine use consistently used more opioids than patients who never used or stopped using benzodiazepines during the study period (one-way ANOVA, P<0.001). For patients with continued and new benzodiazepine use, the odds ratio of long-term opioid use compared with those never prescribed a benzodiazepine was 2.99 (95% CI, 2.89-3.08) and 2.68 (95% CI, 2.62-2.75), respectively.LIMITATIONS: This study used administrative claims analyses, which rely on accuracy and completeness of diagnostic, procedural, and prescription codes.CONCLUSION: Overall opioid prescribing for low back pain or lower extremity pain decreased substantially during the study period, indicating a shift in management within the medical community. Rates of benzodiazepine prescribing, however, remained at approximately 11%. Concurrent prescriptions of benzodiazepines and opioids after LBP or LEP diagnosis were associated with increased risk of long-term opioid use.

    View details for DOI 10.1007/s11606-019-05549-8

    View details for PubMedID 31720966

  • When Global ART Budgets Cannot Cover All Patients, Who Should Be Eligible? JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Zhang, Y., Baernighausen, T., Eyal, N. 2019; 81 (2): 134–37
  • Expenditures and Health Care Utilization Among Adults With Newly Diagnosed LowBack and Lower Extremity Pain JAMA NETWORK OPEN Kim, L. H., Vail, D., Azad, T. D., Bentley, J. P., Zhang, Y., Ho, A. L., Fatemi, P., Feng, A., Varshneya, K., Desai, M., Veeravagu, A., Ratliff, J. K. 2019; 2 (5)
  • Outcomes and costs following Ommaya placement with thrombocytopenia among US cancer patients. World neurosurgery Zhang, M., Zhang, Y., Zheng, E., Gephart, M. H., Veeravagu, A., Desai, A., Ratliff, J. K., Li, G. 2019


    Placement of Ommaya reservoirs for administration of intrathecal chemotherapy may be complicated by comorbid thrombocytopenia among patients with hematologic or leptomeningeal disease. Aggregated data on risks of Ommaya placement among thrombocytopenic patients is lacking. This study assesses complications, revision rates, and costs associated with Ommaya placement among patients with thrombocytopenia in a large population sample.Using a national administrative database, this retrospective study identifies a cohort of adult cancer patients who underwent Ommaya placement between 2007 and 2016. Preoperative thrombocytopenia was defined as diagnosis of secondary thrombocytopenia, bleeding event, procedure to control bleeding, or platelet transfusion, within 30 days prior to index admission. Univariate and multivariate analyses were performed to assess costs, 30-day complications, readmissions, and revisions among patients with and without preoperative thrombocytopenia.The analytic cohort included 1652 patients, of whom 29.3% met criteria for preoperative thrombocytopenia. In-hospital mortality rates were 7.7% among thrombocytopenic patients vs. 1.2% among non-thrombocytopenic patients (p < 0.001). Preoperative thrombocytopenia was associated with 14.5 times greater hazard of intracranial hemorrhage within 30 days following Ommaya placement, occurring in 25.6% vs. 2.0% of thrombocytopenic and non-thrombocytopenic patients, respectively (p < 0.014). Revision rates did not differ significantly between thrombocytopenic and non-thrombocytopenic patients. Thrombocytopenia was associated with longer length of stay (7.4 vs 13.9 days, p < 0.001) and additional $10,000 per patient in costs of index hospitalization (p < 0.001).This is the largest study to date documenting costs and complication rates of Ommaya placement in patients with and without thrombocytopenia.

    View details for DOI 10.1016/j.wneu.2019.12.063

    View details for PubMedID 31866457

  • Appropriate Health Resource Rationing in a Non-Ideal World. Journal of acquired immune deficiency syndromes (1999) Zhang, Y., Bärnighausen, T., Eyal, N. 2019

    View details for DOI 10.1097/QAI.0000000000002127

    View details for PubMedID 31335592