Successful Model for Guideline Implementation to Prevent Cancer-Associated Thrombosis: Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic.

PURPOSE: Guidelines recommend venous thromboembolism (VTE) risk assessment in outpatients with cancer and pharmacologic thromboprophylaxis in selected patients at high risk for VTE. Although validated risk stratification tools are available, < 10% of oncologists use a risk assessment tool, and rates of VTE prophylaxis in high-risk patients are low in practice. We hypothesized that implementation of a systems-based program that uses the electronic health record (EHR) and offers personalized VTE prophylaxis recommendations would increase VTE risk assessment rates in patients initiating outpatient chemotherapy. PATIENTS AND METHODS: Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTEPACC) was a multidisciplinary program implemented by nurses, oncologists, pharmacists, hematologists, advanced practice providers, and quality partners. We prospectively identified high-risk patients using the Khorana and Protecht scores (≥ 3 points) via an EHR-based risk assessment tool. Patients with a predicted high risk of VTE during treatment were offered a hematology consultation to consider VTE prophylaxis. Results of the consultation were communicated to the treating oncologist, and clinical outcomes were tracked. RESULTS: A total of 918 outpatients with cancer initiating cancer-directed therapy were evaluated. VTE monthly education rates increased from < 5% before VTEPACC to 81.6% (standard deviation [SD], 11.9; range, 63.6%-97.7%) during the implementation phase and 94.7% (SD, 4.9; range, 82.1%-100%) for the full 2-year postimplementation phase. In the postimplementation phase, 213 patients (23.2%) were identified as being at high risk for developing a VTE. Referrals to hematology were offered to 151 patients (71%), with 141 patients (93%) being assessed and 93.8% receiving VTE prophylaxis. CONCLUSION: VTEPACC is a successful model for guideline implementation to provide VTE risk assessment and prophylaxis to prevent cancer-associated thrombosis in outpatients. Methods applied can readily translate into practice and overcome the current implementation gaps between guidelines and clinical practice.

Corticomotor excitability of back muscles is affected by intervertebral disc lesion in pigs.

Morphological and behavioural changes in back muscles are common in back pain and injury. Recent data indicate a rapid reduction in the size of the multifidus, a deep back muscle, within 3 days of experimental intervertebral disc (IVD) injury in pigs. A reduced neural drive may contribute to this. We investigated changes in corticomotor excitability following IVD lesion by evaluation of the response of back muscles to electrical stimulation of the motor cortex. Motor evoked potentials (MEPs) were studied in 12 Swedish landrace pigs before injury, immediately after abdominal incision, immediately after L3-4 IVD lesion with a scalpel, and 15 min later. In two animals, responses were also evoked by descending volleys excited at the level of the mastoid processes (cervicomedullary evoked potentials) without motor cortex activation. In five animals, a sham procedure was followed without IVD lesion. MEPs were recorded in short (deep) and long (superficial) fibres of the multifidus at L3-5 on the lesioned side and at L4 contralaterally with intramuscular wire electrodes. Although the MEP amplitude increased in several muscles after incision, at 15 min after IVD lesion only the MEP amplitude of the deep L4 multifidus on the lesioned side was increased [36% (SD 15%), P < 0.05]. There were no changes in MEP amplitude after 15 min at adjacent or contralateral levels. The response to cervicomedullary stimulation reduced slightly. This suggests that the increased MEP amplitude was due to changes in cortical excitability. These data indicate that IVD lesion induces localized increases, and not decreases, in the excitability of cortical inputs to the deep paraspinal muscles that cross a lesioned disc.

Plasmin-matrix metalloproteinase cascades in spinal response to an experimental disc lesion in pig.

STUDY DESIGN: Proteinases were immunohistochemically stained to analyze degenerated discs and paradiscal tissues in comparison to contiguous control tissues in an experimental porcine model of intervertebral disc degeneration. OBJECTIVE: The aim was to analyze plasmin and metalloproteinases known to participate in mutual activation cascades. SUMMARY OF BACKGROUND DATA: Comparison of the degenerated discs and paradiscal structures with control tissues disclosed accumulation of plasmin and induction of matrix metalloproteinases (MMP), MMP-1 and MMP-2 in the discs, but some other MMPs in reactive and remodeling tissues. MATERIAL AND METHODS: In 6 domestic pigs, the cranial L4 endplate was perforated to penetrate the nucleus pulposus. Three months later, the animals were killed and the experimental and the contiguous control vertebrae, complete with their intervertebral discs, were excised and subjected to histologic and immunohistochemical examinations. RESULTS: Immunohistochemical analysis disclosed increased expression of MMP-1 and MMP-2 in the traumatized and degenerated intervertebral discs. Some MMPs were also induced in all paradiscal structures (bone marrow, vertebral bone, and spinal ligaments), or decreased in already scarred areas. The common denominator for all the anatomic sites studied was accumulation of plasmin. CONCLUSION: Fibroblast collagenase (MMP-1) and gelatinase A (MMP-2), capable of degrading native and denatured collagen, were induced in degenerating intervertebral discs. Use of an experimental model enabled demonstration that biomechanical destabilization and degeneration of the disc also affects all other paradiscal structures, which are subjected to proteolysis and/or reparative fibrosis apparently representing remodeling of the spine subjected to pathologic stress. Profiling of various MMPs and plasmin, known to participate in mutual activation cascades, suggests that plasmin could activate pro-MMP-1, pro-MMP-2, pro-MMP-3, pro-MMP-7, pro-MMP-9, and pro-MMP-13 and alone or/and in cooperation with MMP-3 initiate at least 2 mutual MMPs activation cascades driven by activated MMP-3 and MMP-7.

Rapid atrophy of the lumbar multifidus follows experimental disc or nerve root injury.

STUDY DESIGN: Experimental study of muscle changes after lumbar spinal injury. OBJECTIVES: To investigate effects of intervertebral disc and nerve root lesions on cross-sectional area, histology and chemistry of porcine lumbar multifidus. SUMMARY OF BACKGROUND DATA: The multifidus cross-sectional area is reduced in acute and chronic low back pain. Although chronic changes are widespread, acute changes at 1 segment are identified within days of injury. It is uncertain whether changes precede or follow injury, or what is the mechanism. METHODS: The multifidus cross-sectional area was measured in 21 pigs from L1 to S1 with ultrasound before and 3 or 6 days after lesions: incision into L3-L4 disc, medial branch transection of the L3 dorsal ramus, and a sham procedure. Samples from L3 to L5 were studied histologically and chemically. RESULTS: The multifidus cross-sectional area was reduced at L4 ipsilateral to disc lesion but at L4-L6 after nerve lesion. There was no change after sham or on the opposite side. Water and lactate were reduced bilaterally after disc lesion and ipsilateral to nerve lesion. Histology revealed enlargement of adipocytes and clustering of myofibers at multiple levels after disc and nerve lesions. CONCLUSIONS: These data resolve the controversy that the multifidus cross-sectional area reduces rapidly after lumbar injury. Changes after disc lesion affect 1 level with a different distribution to denervation. Such changes may be due to disuse following reflex inhibitory mechanisms.

In vivo porcine intradiscal pressure as a function of external loading.

BACKGROUND: Spinal loading during daily activity as it relates to the ability of the intervertebral disc to sustain its integrity has been a major issue in spinal research. The purpose of this investigation was to establish the relationship between the intervertebral disc pressure in the nucleus and the load applied to the motion segment in an in vivo porcine model. METHODS: Nine domestic pigs were used in this study. A miniaturized servohydraulic testing machine was affixed to the lumbar spine via four intrapedicular screws, which were inserted bilaterally into the L2 and L3 vertebrae. A pressure needle was inserted through the lateral part of the L2-L3 disc annulus and into the nucleus pulposus. Force, deformation, and intradiscal pressure data were collected during a loading scheme that consisted of applying a set of constant loads in increasing order, that is, 50, 100, 150, 200, and 250 N. Each load was applied for 30 seconds followed by 30-second restitution. RESULTS: Intradiscal nucleus pressure was found to correlate to the applied load in all cases. Linear regression analyses resulted in the following equation: intradiscal pressure (MPa) = 0.08 + 1.25E(-3)(load, N), r(2) = 0.81, n = 8. Intradiscal pressure was also highly linearly dependent on the stress. The intrinsic intradiscal pressure was found to be 81 +/- 5 kPa. The results also indicated that the pressure within the disc exhibited a creep behavior. CONCLUSION: In conclusion, pressure in the nucleus of the porcine intervertebral disc was linearly related to the applied load and stress.

Experimental disc degeneration due to endplate injury.

The aim of this study was to create an experimental model of disc degeneration that closely mimicked human disc degeneration. In six domestic pigs, an L4 cranial endplate perforation into the nucleus pulposus was made. Three months postoperatively, compressive testing was performed on the L2-L4 motion segments, and intradiscal pressure was measured in the intervening discs. Histochemical and morphologic examinations were made on the excised degenerated and adjacent discs. A significant reduction in water content was observed in the outer anterior annulus of the degenerated disc. In the nucleus, the proteoglycan content was significantly reduced, as well as the cellularity, although not significantly. The nucleus lost its gel-like structure and was discolored, and there was delamination of annular layers. Intradiscal pressure in the nucleus was significantly lower in the degenerated disc. In conclusion, experimental degeneration of the intervertebral disc induced by endplate penetration resembled human disc degeneration, as exemplified by biochemical and structural changes.