Evaluation of Tacrolimus Concentrations and Clinical Outcomes Between Extended and Immediate Release Formulations in Kidney Transplant.

Objectives: Tacrolimus remains the mainstay of immunosuppression in kidney transplantation. Understanding the relationship between therapeutic tacrolimus levels and outcomes of acute rejection, patient/graft survival, and tolerability are important. The relationship between time to therapeutic tacrolimus levels and outcomes has not been well established, specifically with the use of extended release tacrolimus formulation (LCP-Tac). This study investigated time to therapeutic tacrolimus levels of 2 tacrolimus formulations, LCP-Tac and immediate release tacrolimus (IR-Tac), as a predictor of clinical outcomes. Methods: This was a single-center, retrospective, cohort study of kidney transplant recipients at Duke Hospital between 2013-2021. The primary objective evaluated the difference in time to therapeutic tacrolimus levels with LCP-Tac vs IR-Tac regimens. Secondary endpoints included time within therapeutic range during the first 3 months post-transplant, incidence of biopsy-proven rejection, development of de novo donor specific antibodies, and patient and allograft survival at 12 months post-transplant. Results: 128 patients were included (63 in LCP-Tac group and 65 in IR-Tac group). The time to therapeutic tacrolimus level was similar between formulations (7.2 days with LCP-Tac compared to 6.7 days with IR-Tac, P = .63). The time within therapeutic range during the first 3 months post-transplant, via modified Rosendaal, was similar with LCP-Tac and IR-Tac (56.1% vs 64.8%, respectively). Rates of biopsy-proven acute rejection at 12 months were similar (7/63 (11.1%) compared to 4/65 (6.2%)). There was no difference in patient/graft survival between groups. Conclusions: The time to therapeutic tacrolimus levels did not differ based on tacrolimus formulation and was not correlated with clinical outcomes.

Disparities in the treatment of movement disorders using deep brain stimulation.

OBJECTIVE: Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) and essential tremor (ET). Although the prevalence of PD and ET can vary by sex and race, little is known about the accessibility of neurosurgical treatments for these conditions. In this nationwide study, the authors aimed to characterize trends in the use of DBS for the treatment of PD and ET and to identify disparities in the neurosurgical treatment of these diseases based on ethnic, racial, sex, insurance, income, hospital, and geographic factors. METHODS: Using the dates January 1, 2012, to December 31, 2019, the authors queried the National Inpatient Sample database for all discharges with an ICD-9 or ICD-10 diagnosis of PD or ET. Among these discharges, the DBS rates were reported for each subgroup of race, ethnicity, and sex. To develop national estimates, all analyses were weighted. RESULTS: Among 2,517,639 discharges with PD, 29,820 (1.2%) received DBS, and among 652,935 discharges with ET, 11,885 (1.8%) received DBS. Amid the PD cases, Black patients (n = 405 [0.2%], OR 0.16, 95% CI 0.12-0.20) were less likely than White patients (n = 23,975 [1.2%]) to receive DBS treatment, as were Hispanic patients (n = 1965 [1.1%], OR 0.76, 95% CI 0.65-0.88), whereas Asian/Pacific Islander patients (n = 855 [1.5%]) did not statistically differ from White patients. Amid the ET cases, Black (n = 230 [0.8%], OR 0.39, 95% CI 0.27-0.56), Hispanic (n = 215 [1.0%], OR 0.39, 95% CI 0.28-0.55), and Asian/Pacific Islander (n = 55 [1.0%], OR 0.51, 95% CI 0.28-0.93) patients were less likely than White patients (n = 10,440 [1.9%]) to receive DBS. Females were less likely than males to receive DBS for PD (OR 0.69, p < 0.0001) or ET (OR 0.70, p < 0.0001). CONCLUSIONS: The authors describe significant racial and sex-based differences in the utilization of DBS for the treatment of PD and ET. Further research is required to ascertain the causes of these disparities, as well as any differences in access to specialty neurosurgical care and referral for neuromodulation approaches.

Healthcare resource utilization for chronic low back pain among high-utilizers.

BACKGROUND: Chronic low back pain is a leading cause of morbidity and is among the largest cost drivers for the healthcare system. Research on healthcare resource utilization of patients with low back pain who are not surgical candidates is limited, and few studies follow individuals who generate high healthcare costs over time. PURPOSE: This claims study aimed to identify patients with high-impact mechanical, chronic low back pain (CLBP), quantify their low back pain-related health resource utilization, and explore associated patient characteristics. We hypothesize that patients in the top quartile of healthcare resource utilization in the second year after initial diagnosis will continue to generate considerable back pain-related costs in subsequent years. STUDY DESIGN/SETTING: IBM MarketScan Research Databases from 2009-2019 were retrospectively analyzed. PATIENT SAMPLE: Adults in the United States with an initial diagnosis of low back pain between 2010 and 2014 who did not have cancer, spine surgery, recent pregnancy, or inflammatory spine conditions, were identified using the International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes. To ensure patients had chronic low back pain, it was required that individuals had additional claims with a low back pain diagnosis 6 to 12 and 12 to 24 months after initial diagnosis. OUTCOME MEASURES: Cost and utilization of inpatient visits, outpatient visits, emergency room visits, pharmacologic and nonpharmacologic treatment options and imaging for chronic low back pain. METHODS: Annual back pain-related costs and the use of pharmacologic and nonpharmacologic treatments for 5 years were analyzed. Logistic regression was utilized to identify factors associated with persistent high spending. RESULTS: Of 16,917 individuals who met the criteria for chronic low back pain, 4,229 met the criteria for having high healthcare utilization, defined as being in the top quartile of back pain-related costs in the 12 to 24 months after their initial diagnosis. The mean and median back pain-related cost in the first year after an initial diagnosis was $7,112 (SD $9,670) and $4,405 (Q1 $2,147, Q3 $8,461). Mean and median back pain related costs in the second year were $11,989 (SD $20,316) and $5,935 (Q1 $3,892, Q3 $10,678). Costs continued to be incurred in years 3 to 5 at a reduced rate. The cumulative mean cost for back pain over the 5 years following the initial diagnosis was $31,459 (SD $39,545). The majority of costs were from outpatient services. Almost a quarter of the high utilizers remained in the top quartile of back pain-related costs during years 3 to 5 after the initial diagnosis, and another 19% remained in the top quartile for 2 of the 3 subsequent years. For these two groups combined (42%), the 5-year cumulative mean cost for back pain was $43,818 (SD $48,270). Patient characteristics associated with a higher likelihood of remaining as high utilizers were diabetes, having a greater number of outpatient visits and pharmacologic prescriptions, and lower utilization of imaging services. CONCLUSION: This is one of the first studies to use an administrative claims database to identify high healthcare resource utilizers among a population of United States individuals with nonsurgical, chronic low back pain and follow their utilization over time. There was a population of individuals who continued to experience high costs 5 years beyond their initial diagnosis, and the majority of individuals continued to seek outpatient services. Further longitudinal claims research that incorporates symptom severity is needed to understand the economic implications of this condition.

Disparities in Access to Deep Brain Stimulation and Responsive Neurostimulation Approaches to Drug-Resistant Epilepsy.

BACKGROUND: Epilepsy affects 1% to 2% of the global population, and those who are resistant to medical treatment may be candidates for neuromodulation. In select populations, brain stimulation approaches including deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used. Although studies have shown that patients from Black, Hispanic, lower income, and rural communities have less access to epilepsy care and have lower rates of epilepsy surgery, disparities in the use of brain stimulation for epilepsy treatment are currently not known. MATERIALS AND METHODS: We queried the US National Inpatient Sample data base from January 1, 2014 to December 31, 2019 for all patients discharged with an International Classification of Diseases (ICD) Ninth Revision or ICD Tenth Revision diagnosis of drug-resistant epilepsy. Among these patients discharged, the rates of brain stimulation treatment, including DBS and RNS, were reported in each subgroup of race, ethnicity, and insurance. To generate national estimates, all analyses were weighted. RESULTS: A total of 237,895 patients discharged with drug-resistant epilepsy were identified, of whom 4,925 (2.1%) received brain stimulation treatment for drug-resistant epilepsy. Black patients (n = 420, 0.9%, odds ratio [OR] = 0.51, 95% CI [0.40, 0.64]) were less likely to receive brain stimulation treatment than were White patients (n = 3300, 2.4%). There was no significant difference between Asian (n = 105, 2.3%, OR = 0.80, 95% CI [0.53, 1.33]) and Hispanic (n = 655, 2.6%, OR = 0.95, 95% CI [0.77, 1.17]) patients and White patients. No significant difference was observed between female (n = 2515, 2.1%, OR = 1.02, 95% CI [0.89, 1.17]) and male (n = 2410, 2.0%) patients either. Patients with Medicare (n = 1150, 1.2%, OR = 0.69, 95% CI [0.57, 0.84]) or Medicaid (n = 1150, 1.8%, OR = 0.52, 95% CI [0.44, 0.62]) were less likely to receive brain stimulation treatment than were those with private insurance as the primary payer (n = 2370, 3.9%). CONCLUSIONS: We discovered significant disparities in the use of brain stimulation treatments for drug-resistant epilepsy based on race and insurance status. More research will be required to determine the cause of these disparities.

Two-Year Clinical and Radiographic Outcomes for Percutaneous Lumbar Interbody Fusion With an Expandable Titanium Cage Through Kambin's Triangle Without Facetectomy.

BACKGROUND: There has been heightened interest in performing percutaneous lumbar interbody fusions (percLIFs) through Kambin's triangle, an anatomic corridor allowing entrance into the disc space. However, due to its novelty, there are limited data regarding the long-term benefits of this procedure. Our objective was to determine the long-term efficacy and durability of the percutaneous insertion of an expandable titanium cage through Kambin's triangle without facetectomy. METHODS: A retrospective review of patients undergoing percLIF via Kambin's triangle using an expandable titanium cage was performed. Demographics, visual analog scale (VAS) scores, Oswestry Disability Index (ODI), radiographic measurements, perioperative variables, and complications were recorded. VAS, ODI, and radiographic measurements were compared with baseline using the generalized estimating equations assuming normally distributed data. Fusion was assessed with computed tomography (CT) at 1 and 2 years after the procedure. RESULTS: A total of 49 patients were included. Spondylolisthesis, lumbar lordosis (LL), sacral slope, pelvic tilt, and anterior/posterior disc space height were all significantly improved postoperatively at each time point of 3, 6, 12, and 24 months (P < 0.001). Pelvic incidence-LL mismatch decreased significantly at each follow-up (P < 0.001) with a mean reduction of 4° by 24 months. VAS back scores reduced by >2 points at the 6, 12, and 24 month follow-ups. ODI scores reduced by >15 points at the 12- and 24-month follow-ups. Of the patients who had 1- and 2-year CT images, fusion rates at those time points were 94.4% (17/18) and 87.5% (7/8), respectively. The mean annual rate of surgically significant adjacent segment disease was 2.74% through an average follow-up of 2.74 years. CONCLUSION: These results highlight that percLIF, a procedure done without an endoscope or facetectomy, can be performed using an expandable titanium cage through Kambin's triangle with excellent radiographic and clinical results. CLINICAL RELEVANCE: percLIF via Kambin's triangle is a safe and succesful procedure with long-term improvements in both clinical and radiographic outcomes.

Quantifying the Opportunity Cost of Neurosurgical Resident Education.

BACKGROUND/OBJECTIVE: Education is at the core of neurosurgical residency, but little research in to the cost of neurosurgical education exists. This study aimed to quantify costs of resident education in an academic neurosurgery program using traditional teaching methods and the Surgical Autonomy Program (SAP), a structured training program. METHODS: SAP assesses autonomy by categorizing cases into zones of proximal development (opening, exposure, key section, and closing). All first-time, 1-level to 4-level anterior cervical discectomy and fusion (ACDF) cases between March 2014 and March 2022 from 1 attending surgeon were divided into 3 groups: independent cases, cases with traditional resident teaching, and cases with SAP teaching. Surgical times for all cases were collected and compared within levels of surgery between groups. RESULTS: The study found 2140 ACDF cases, with 1758 independent, 223 with traditional teaching, and 159 with SAP. For 1-level to 4-level ACDFs, teaching took longer than it did with independent cases, with SAP teaching adding additional time. A 1-level ACDF performed with a resident (100.1 ± 24.3 minutes) took about as long as a 3-level ACDF performed independently (97.1 ± 8.9 minutes). The average time for 2-level cases was 72.0 ± 18.2 minutes independently, 121.7 ± 33.7 minutes traditional, and 143.4 ± 34.9 minutes SAP, with significant differences among all groups. CONCLUSIONS: Teaching takes significant time compared with operating independently. There is also a financial cost to educating residents, because operating room time is expensive. Because attending neurosurgeons lose time to perform more surgeries when teaching residents, there is a need to acknowledge surgeons who devote time to training the next generation of neurosurgeons.

Assessment of Health Care Costs and Total Baclofen Use Associated With Targeted Drug Delivery for Spasticity.

BACKGROUND: Chronic spasticity causes significant impairment and financial burden. Oral baclofen, the first-line therapy, can have intolerable, dose-dependent side effects. Targeted drug delivery (TDD) through intrathecal baclofen delivers smaller amounts of baclofen into the thecal sac via an implanted infusion system. However, the health care resource utilization of patients with spasticity receiving TDD has not been studied extensively. MATERIALS AND METHODS: Adult patients who received TDD for spasticity between 2009 and 2017 were identified using the IBM MarketScan® data bases. Patients' use of oral baclofen and health care costs were examined at baseline (one year before implantation) and three years after implantation. A multivariable regression model using the generalized estimating equations method and a log link function was used to compare postimplantation costs with those at baseline. RESULTS: The study identified 771 patients with TDD for medication analysis and 576 for cost analysis. At baseline, the median costs were $39,326 (interquartile range [IQR]: $19,526-$80,679), which increased to $75,728 (IQR: $44,199-$122,676) in year 1, decreased to $27,160 (IQR: $11,896-$62,427) in year 2, and increased slightly to $28,008 (IQR: $11,771-$61,885) in year 3. In multivariable analysis, the cost was 47% higher than at baseline (cost ratio [CR] 1.47, 95% CI: 1.32-1.63) in year 1 but was 25% lower (CR 0.75, 95% CI: 0.66-0.86) in year 2 and 32% lower (CR 0.68, 95% CI: 0.59-0.79) in year 3. Before implant, 58% of patients took oral baclofen, which decreased to 24% by year 3. The median daily baclofen dose decreased from 61.8 mg (IQR: 40-86.4) before TDD to 32.8 mg (IQR: 30-65.7) three years later. CONCLUSIONS: Our findings indicate that patients who undergo TDD use less oral baclofen, potentially reducing the risk of side effects. Although total health care costs increased immediately after TDD, most likely owing to device and implantation costs, they decreased below baseline after one year. The costs of TDD reach cost neutrality approximately three years after implant, indicating its potential for long-term cost savings.