Comparison of Vertebroplasty, Kyphoplasty, and Nonsurgical Management of Vertebral Compression Fractures and Impact on US Healthcare Resource Utilization

Study DesignRetrospective propensity score-matched cohort analysis of the Thomson Reuters MarketScan database.PurposeTo compare the outcomes of vertebral compression fracture (VCF) treatment options, with an emphasis on reoperation, complications, costand overall healthcare resource use between 2005 and 2009 in the United States.Overview of LiteratureOptions for the treatment of VCFs include conservative management, kyphoplasty, and vertebroplasty. The cost-effectiveness of surgical intervention for VCF has been criticized, and some suggest their outcomes to be similar to placebo.MethodsPatients 18 years of age and older who developed a VCF were identified and separated into three treatment cohorts: vertebroplasty, kyphoplasty, and non-surgical. Propensity score matching was performed to match patients between cohorts. Main outcomes assessed included reoperation, complications, healthcare resource use and associated cost. Outcomes were compared at three separate time intervals (patients at index hospitalization; patients with at least 2-year follow-up data; and those with at least 4-year follow-up data).ResultsTwenty thousand seven hundred forty patients were identified with VCFs, yielding 7,290 after propensity score matching. The mean age of the patients was 78±12 years; and 5,507 (75.5%) were female. All reoperation rates ranged from 6%-17%, while complication rates ranged from 7%-10%, which did not differ significantly among the three cohorts at all follow-up periods. Overall costs were noted to be significantly greater in both the kyphoplasty and vertebroplasty groups at 1-year follow-up, not at 2-year and 4-year follow-up.ConclusionsOur data suggests that the treatment of a VCF patient will likely be associated with similar long-term operative and complication rates regardless of treatment modality

Cost-effectiveness of 10-kHz Spinal Cord Stimulation Therapy Compared With Conventional Medical Management Over the First 12 Months of Therapy for Patients With Nonsurgical Back Pain: Randomized Controlled Trial

Objective: This analysis evaluated if spinal cord stimulation (SCS) at 10 kHz plus conventional medical management (CMM) is cost-effective compared with CMM alone for the treatment of nonsurgical refractory back pain (NSRBP). Methods: NSRBP subjects were randomized 1:1 into the 10-kHz SCS (n = 83) or CMM (n = 76) group. Outcomes assessed at 6 months included EQ-5D 5-level (EQ-5D-5L), medication usage, and healthcare utilization (HCU). There was an optional crossover at 6 months and follow-up to 12 months. The incremental cost-effectiveness ratio (ICER) was calculated with cost including all HCU and medications except for the initial device and implant procedure, and cost-effectiveness was analyzed based on a willingness-to-pay threshold of \u3c $50,000 per quality-adjusted life-year. Results: Treatment with 10-kHz SCS resulted in a significant improvement in quality of life (QOL) over CMM (EQ-5D-5L index score change of 0.201 vs -0.042, p \u3c 0.001) at a lower cost, based on reduced frequency of HCU resulting in an ICER of -$4964 at 12 months. The ICER was -$8620 comparing the 6 months on CMM with postcrossover on 10-kHz SCS. Conclusions: Treatment with 10-kHz SCS provides higher QOL at a lower average cost per patient compared with CMM. Assuming an average reimbursement for device and procedure, 10-kHz SCS therapy is predicted to be cost-effective for the treatment of NSRBP compared with CMM within 2.1 years

Durability of high-frequency 10-kHz spinal cord stimulation for patients with painful diabetic neuropathy refractory to conventional treatments: 12-month results from a randomized controlled trial

No abstract available

A randomized controlled trial of high frequency (10 kHz) spinal cord stimulation in painful diabetic neuropathy

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments. Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN). Design, Setting, and Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated. Interventions: Implanted medical device delivering 10-kHz SCS. Main Outcomes and Measures: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months. Results: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001). Conclusions and Relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN. Trial Registration: ClincalTrials.gov Identifier: NCT0322842

Nerve growth factor: structure, function and therapeutic implications for Alzheimer\u27s disease.

Over the past decade, neurotrophic factors have generated much excitement for their potential as therapy for neurological disorders. In this regard, nerve growth factor (NGF), the founding member of the neurotrophin family, has generated great interest as a potential target for the treatment of Alzheimer\u27s disease (AD). This interest is based on the observation that cholinergic basal forebrain (CBF) neurons which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus undergo selective and severe degeneration in advanced AD and that these neurons are dependent upon NGF and its receptors for their survival. In fact, NGF transduces its effects by binding two classes of cell surface receptors, TrkA and p75(NTR), both of which are produced by CBF neurons. This review focuses on NGF/receptor binding, signal transduction, regulation of specific cellular endpoints, and the potential use of NGF in AD. Alterations in NGF ligand and receptor expression at different stages of AD are summarized. Recent results suggest that cognitive deficits in early AD and mild cognitive impairment (MCI) are not associated with a cholinergic deficit. Thus, the earliest cognitive deficits in AD may involve brain changes other than simply cholinergic system dysfunction. Recent findings indicate an early defect in NGF receptor expression in CBF neurons; therefore treatments aimed at facilitating NGF actions may prove highly beneficial in counteracting the cholinergic dysfunction found in end-stage AD and attenuating the rate of degeneration of these cholinergic neurons

The source driving membrane polarization with three different electrode designs.

<p>(a) Examples of the centered second difference of the potentials (Δ²Φ) along two dorsal column (DC) fibers and two dorsal root (DR) fibers. The grey boxes indicate regions where changes in tissue conductivity caused abrupt changes in Δ²Φ. (b) The range of maximum Δ²Φ across across all modeled DC fibers and DR fibers for three electrode configurations. LT = longitudinal tripolar, TT = transverse tripolar, AT = angular tripolar, and the number after the hyphen indicates the interelectrode spacing in mm.</p

Selectivity of five tripolar electrode designs in model of Patient 2.

<p>(a) The percent of dorsal column (DC) fibers activated with no dorsal root (DR) fiber activation (<i>i.e.,</i> DC₀) when the electrode was placed along the midline, 1 mm above (<i>top</i>) and below (<i>bottom</i>) the spinal cord. DC₀ is shown above the spinal cord. For comparison, the range of DC₀ across all patients is shown below each panel. (b) Proportion of DC fibers activated versus proportions of the DR fibers activated (<i>i.e.,</i> DC_X) for three electrode designs in the extradural (<i>left</i>) and intradural (<i>right</i>) cases. The inset shows a close-up of the curves. LT = longitudinal tripolar, TT = transverse tripolar, AT = angular tripolar, and the number after the hyphen indicates the interelectrode spacing in mm.</p

Five SCS electrode designs evaluated with the computational model.

<p>(a) Medtronic Models 3776/3876 (<i>left</i>) and 3777/3877 (<i>right</i>) in longitudinal tripolar configurations. (b) St. Jude Medical Penta in two transverse tripolar configurations. (c) A transverse view of a novel percutaneous lead with an azimuthal array of electrodes in a tripolar configuration. Inactive contacts were not represented.</p

The selectivity of extradural SCS versus intradural SCS in model of Patient 5.

<p>The maximum percentage of dorsal column (DC) fibers activated with no activation of dorsal root (DR) fibers (DC₀) when the array was placed in the extradural (<i>top row</i>) and intradural (<i>bottom row</i>) spaces at lateral deviations of 0° (<i>left column</i>), −10° (<i>middle column</i>), and −20° (<i>right column</i>). For comparison, the range of DC₀ across all patients is shown below each panel. (b) Curves of the proportion of DC fibers activated versus proportion of DR fibers activated for three different electrode locations along the midline.</p

Spinal cord geometry from individual patients^a.

a<p>Geometries were measured from MRI images (at 1.5 Tesla) with a resolution of 1 mm.</p>b<p>Placement with respect to midline.</p>c<p>Spinal cord center placed at the center of the elliptical shell defining the dura mater.</p>d<p>The spinal cord center was twice as far from the dorsal interior surface of the dura mater as it was from the ventral interior surface of the dura mater.</p><p>Spinal cord geometry from individual patients^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0114938#nt103" target="_blank">a</a>}.</p