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.

A national report of nursing home information technology: year 1 results.

OBJECTIVE: To provide a report on year 1 results of a national study investigating nursing home information technology (IT) adoption, called IT sophistication. METHODS: A reliable and valid survey was used to measure IT sophistication. The target goal was 10% from each state in the United States, 1570 nursing homes. A random sample of homes from each state was recruited from Nursing Home Compare. RESULTS: The team reached 2627 nursing home administrators, among whom 1799 administrators agreed to participate and were sent a survey. A total of 815 surveys were completed (45.3% response rate), which was below the goal. Facilities in the participating sample have similar demographic characteristics (ownership, total population in a location, and bed size) to the remaining homes not participating. There are greater IT capabilities in resident care and administrative activities, less in clinical support. The extent of use of these capabilities appears to be highest in administrative activities and lowest in clinical support. IT in resident care appears to be the most integrated with internal and external stakeholders. IT capabilities appear to be greater than IT extent of use in all health domains, with the greatest difference in resident care. DISCUSSION: National evaluations of nursing home IT are rare. Measuring trends in IT adoption in a nationally representative sample provides meaningful analytics that could be more useful for policy makers and nursing home leaders in the future. CONCLUSION: Discovering national baseline assessments is a first step toward recognizing nursing home trends in IT adoption.

Effects of electrical nerve stimulation on force generation, oxygenation and blood volume in muscles of the immobilized human leg.

BACKGROUND: Transcutaneous electrical stimulation of the common peroneal nerve may be an additional clinical tool for enhancing venous return by active and passive mechanisms of muscle action in the immobilized leg. PURPOSES: To determine the effects of electrical stimulation of the common peroneal nerve to (1) produce force during isometric ankle joint dorsiflexion, and (2) alter muscle oxygenation and blood volume in the resting human leg. METHODS: A novel electrical stimulator was applied to 28 legs of 14 healthy subjects. The force during isometric ankle joint dorsiflexion and myoelectric responses produced by stimulation-induced leg muscle contractions were investigated. Muscle oxygen saturation, blood volume and deoxygenated haemoglobin in the tibialis anterior and medial gastrocnemius muscles were measured by near-infrared spectroscopy during venous stasis (40 mmHg thigh tourniquet), with or without electrical stimulation. Results. The force produced during ankle joint dorsiflexion at the maximal stimulation intensity was 2.25 N (0.02-14.14) in the resting leg. Changes in muscle oxygen saturation during venous stasis, with or without electrical stimulation, were similar. Electrical stimulation during venous stasis caused 4-9% and 0.2-6% less increase in total muscle blood volume and deoxygenated hemoglobin compared to venous stasis alone. CONCLUSIONS: Nerve stimulation with a newly developed device partly counteracts increases in muscle blood volume and deoxygenated hemoglobin of the resting leg during venous stasis. CLINICAL RELEVANCE: The device stimulates active and passive mechanisms of leg muscle action that seems to enhance venous return in patients with impaired function.

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.

Bulging of the inner and outer annulus during in vivo axial loading of normal and degenerated discs.

STUDY DESIGN: Comparison of in vivo biomechanical outcomes between experimental and control group animals. OBJECTIVE: To quantify the in vivo bulging response of the inner and outer annulus in animals with and without disc degeneration. SUMMARY OF BACKGROUND DATA: Prior attempts to quantify the load-deformation response of the inner annulus have most often relied on in vitro preparations. Unfortunately, to visualize the inner annulus, these in vitro approaches rely on disc modifications that may result in nonphysiologic behaviors. In response to this problem, in vivo techniques were developed to quantify regional bulging of the inner and outer annulus during applied axial loading. METHODS: Two groups of pigs were tested: a normal group and a group having disc degeneration that was induced surgically 3 months earlier. Eight adolescent pigs were evaluated and for each animal, a miniature servohydraulic actuator was attached to the third and fourth lumbar vertebrae to deliver a cyclic axial loading protocol (300 N, 1 Hz, 10 cycles) whereas regional deformations of the annulus were visualized ultrasonically via retroperitoneal access. RESULTS: For the normal animals, image analysis demonstrated a significantly greater bulging of the inner annular region when compared with the outer annular region. In animals with disc degeneration, the inner and outer annular regions were equal in their bulging response, which ranged from 0 bulging to 37% greater than the average response of the normal animals. CONCLUSIONS: This work supports prior in vitro studies that observed maximal disc bulging in the inner annulus and minimal bulging in the external annulus. Results for this in vivo study suggest that this normal bulging gradient is lost with degenerative disc disease. Compared with in vitro approaches, this new in vivo technique has the potential to demonstrate disc behavior in a variety of loading conditions and/or with a variety of induced disc pathologies.

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.

Pemphigus, pregnancy, and plasmapheresis.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder that usually occurs in the fifth and sixth decades of life but may occur at younger ages and during pregnancy. Circulating intercellular antibodies directed at desmosomal proteins may cross the placenta and place children at risk for neonatal pemphigus (NP). We describe the case of a pregnant woman with PV treated successfully with a combination of systemic corticosteroids and plasmapheresis. The possibility of PV should be considered in any pregnant woman with a worsening, widespread, mucocutaneous, blistering disease. Plasmapheresis offers a useful alternative to immunosuppressive therapy in the setting of pregnancy.

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.

Intervertebral stiffness of the spine is increased by evoked contraction of transversus abdominis and the diaphragm: in vivo porcine studies.

STUDY DESIGN: In vivo porcine study of intervertebral kinematics. OBJECTIVES: This study investigated the effect of transversus abdominis and diaphragm activity, and increased intra-abdominal pressure on intervertebral kinematics in porcine lumbar spines. BACKGROUND: Studies of trunk muscle recruitment in humans suggest that diaphragm and transversus abdominis activity, and the associated intra-abdominal pressure contribute to the control of intervertebral motion. However, this has not been tested in vivo. METHODS: Relative intervertebral motion of the L3 and L4 vertebrae and the stiffness at L4 were measured in response to displacements of the L4 vertebra imposed via a device fixed to the L4 vertebral body. In separate trials, diaphragm and transversus abdominis activity was evoked by stimulation of the phrenic nerves and via electrodes threaded through the abdominal wall. RESULTS: When intra-abdominal pressure was increased by diaphragm or transversus abdominis stimulation, the relative intervertebral displacement of the L3 and L4 vertebrae was reduced and the stiffness of L4 was increased for caudal displacements. There was no change in either parameter for rostral displacements. In separate trials, the diaphragm crurae and the fascial attachments of transversus abdominis were cut, but intra-abdominal pressure was increased. In these trials, the reduction in intervertebral motion was similar to trials with intact attachments for caudal motion, but was increased for rostral trials. CONCLUSIONS: The results of these studies indicate that elevated intra-abdominal pressure, and contraction of diaphragm and transversus abdominis provide a mechanical contribution to the control of spinal intervertebral stiffness. Furthermore, the effect is modified by the muscular attachments to the spine.