Differential Attrition

The differential attrition of persons from comparison groups severely restricts the inferences that can be made from results of evaluative research. This problem is particularly troublesome in the evaluation of medical technologies, such as coronary artery bypass graft surgery, since a substantial percentage of medical or control patients cross over to the surgical group. A procedure using worst case assumptions is developed that allows researchers to estimate the maximum effect of differential attrition, and therefore enhance the quality of their inferences. The article first illustrates theprocedure, then concludes with a discussion of the generality of the estimation procedure to other instances in which differential attrition is a problem, and points out the limitations of the approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67927/2/10.1177_0193841X8300700607.pd

Delayed Effects of Radiofrequency Energy on Accessory Atrioventricular Connections

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74618/1/j.1540-8159.1993.tb04574.x.pd

Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

Local biochemical and morphological differences in human Achilles tendinopathy: a case control study

<p>Abstract</p> <p>Background</p> <p>The incidence of Achilles tendinopathy is high and underlying etiology as well as biochemical and morphological pathology associated with the disease is largely unknown. The aim of the present study was to describe biochemical and morphological differences in chronic Achilles tendinopathy. The expressions of growth factors, inflammatory mediators and tendon morphology were determined in both chronically diseased and healthy tendon parts.</p> <p>Methods</p> <p>Thirty Achilles tendinopathy patients were randomized to an expression-study (<it>n </it>= 16) or a structural-study (<it>n </it>= 14). Biopsies from two areas in the Achilles tendon were taken and structural parameters: fibril density, fibril size, volume fraction of cells and the nucleus/cytoplasm ratio of cells were determined. Further gene expressions of various genes were analyzed.</p> <p>Results</p> <p>Significantly smaller collagen fibrils and a higher volume fraction of cells were observed in the tendinopathic region of the tendon. Markers for collagen and its synthesis collagen 1, collagen 3, fibronectin, tenascin-c, transforming growth factor-β fibromodulin, and markers of collagen breakdown matrix metalloproteinase-2, matrix metalloproteinase-9 and metallopeptidase inhibitor-2 were significantly increased in the tendinopathic region. No altered expressions of markers for fibrillogenesis, inflammation or wound healing were observed.</p> <p>Conclusion</p> <p>The present study indicates that an increased expression of factors stimulating the turnover of connective tissue is present in the diseased part of tendinopathic tendons, associated with an increased number of cells in the injured area as well as an increased number of smaller and thinner fibrils in the diseased tendon region. As no fibrillogenesis, inflammation or wound healing could be detected, the present data supports the notion that tendinopathy is an ongoing degenerative process.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN20896880">ISRCTN20896880</a></p

Could it be advantageous to tune the temperature controller during radiofrequency ablation? A feasibility study using theoretical models

Purpose: To assess whether tailoring the Kp and Ki values of a proportional-integral (PI) controller during radiofrequency (RF) cardiac ablation could be advantageous from the point of view of the dynamic behaviour of the controller, in particular, whether control action could be speeded up and larger lesions obtained. Methods: Theoretical models were built and solved by the finite element method. RF cardiac ablations were simulated with temperature controlled at 55 degrees C. Specific PI controllers were implemented with Kp and Ki parameters adapted to cases with different tissue values (specific heat, thermal conductivity and electrical conductivity) electrode-tissue contact characteristics (insertion depth, cooling effect of circulating blood) and electrode characteristics (size, location and arrangement of the temperature sensor in the electrode). Results: The lesion dimensions and T(max) remained almost unchanged when the specific PI controller was used instead of one tuned for the standard case: T(max) varied less than 1.9 degrees C, lesion width less than 0.2 mm, and lesion depth less than 0.3 mm. As expected, we did observe a direct logical relationship between the response time of each controller and the transient value of electrode temperature. Conclusion: The results suggest that a PI controller designed for a standard case (such as that described in this study), could offer benefits under different tissue conditions, electrode-tissue contact, and electrode characteristics.This work received financial support from the Spanish 'Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion' Grant no. TEC2008-01369/TEC and FEDER Project MTM2010-14909. The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain. The authors alone are responsible for the content and writing of the paperAlba Martínez, J.; Trujillo Guillen, M.; Blasco Giménez, RM.; Berjano Zanón, E. (2011). Could it be advantageous to tune the temperature controller during radiofrequency ablation? A feasibility study using theoretical models. International Journal of Hyperthermia. 27(6):539-548. https://doi.org/10.3109/02656736.2011.586665S539548276Gaita, F., Caponi, D., Pianelli, M., Scaglione, M., Toso, E., Cesarani, F., … Leclercq, J. F. (2010). Radiofrequency Catheter Ablation of Atrial Fibrillation: A Cause of Silent Thromboembolism? Circulation, 122(17), 1667-1673. doi:10.1161/circulationaha.110.937953Anfinsen, O.-G., Aass, H., Kongsgaard, E., Foerster, A., Scott, H., & Amlie, J. P. (1999). Journal of Interventional Cardiac Electrophysiology, 3(4), 343-351. doi:10.1023/a:1009840004782PETERSEN, H. H., CHEN, X., PIETERSEN, A., SVENDSEN, J. H., & HAUNSO, S. (2000). Tissue Temperatures and Lesion Size During Irrigated Tip Catheter Radiofrequency Ablation: An In Vitro Comparison of Temperature-Controlled Irrigated Tip Ablation, Power-Controlled Irrigated Tip Ablation, and Standard Temperature-Controlled Ablation. Pacing and Clinical Electrophysiology, 23(1), 8-17. doi:10.1111/j.1540-8159.2000.tb00644.xTungjitkusolmun, S., Woo, E. J., Cao, H., Tsai, J. Z., Vorperian, V. R., & Webster, J. G. (2000). Thermal—electrical finite element modelling for radio frequency cardiac ablation: Effects of changes in myocardial properties. Medical & Biological Engineering & Computing, 38(5), 562-568. doi:10.1007/bf02345754Lai, Y.-C., Choy, Y. B., Haemmerich, D., Vorperian, V. R., & Webster, J. G. (2004). Lesion Size Estimator of Cardiac Radiofrequency Ablation at Different Common Locations With Different Tip Temperatures. IEEE Transactions on Biomedical Engineering, 51(10), 1859-1864. doi:10.1109/tbme.2004.831529Jain, M. K., & Wolf, P. D. (1999). Temperature-controlled and constant-power radio-frequency ablation: what affects lesion growth? IEEE Transactions on Biomedical Engineering, 46(12), 1405-1412. doi:10.1109/10.804568Panescu, D., Whayne, J. G., Fleischman, S. D., Mirotznik, M. S., Swanson, D. K., & Webster, J. G. (1995). Three-dimensional finite element analysis of current density and temperature distributions during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 42(9), 879-890. doi:10.1109/10.412649Hong Cao, Vorperian, V. R., Tungjitkusolmun, S., Jan-Zern Tsai, Haemmerich, D., Young Bin Choy, & Webster, J. G. (2001). Flow effect on lesion formation in RF cardiac catheter ablation. IEEE Transactions on Biomedical Engineering, 48(4), 425-433. doi:10.1109/10.915708Tungjitkusolmun, S., Vorperian, V. R., Bhavaraju, N., Cao, H., Tsai, J.-Z., & Webster, J. G. (2001). Guidelines for predicting lesion size at common endocardial locations during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 48(2), 194-201. doi:10.1109/10.909640Schutt, D., Berjano, E. J., & Haemmerich, D. (2009). Effect of electrode thermal conductivity in cardiac radiofrequency catheter ablation: A computational modeling study. International Journal of Hyperthermia, 25(2), 99-107. doi:10.1080/02656730802563051Langberg, J. J., Calkins, H., el-Atassi, R., Borganelli, M., Leon, A., Kalbfleisch, S. J., & Morady, F. (1992). Temperature monitoring during radiofrequency catheter ablation of accessory pathways. Circulation, 86(5), 1469-1474. doi:10.1161/01.cir.86.5.1469Calkins, H., Prystowsky, E., Carlson, M., Klein, L. S., Saul, J. P., & Gillette, P. (1994). Temperature monitoring during radiofrequency catheter ablation procedures using closed loop control. Atakr Multicenter Investigators Group. Circulation, 90(3), 1279-1286. doi:10.1161/01.cir.90.3.1279Lennox CD, Temperature controlled RF coagulation. Patent number: 5.122.137 Hudson NHEdwards SD, Stern RA, Electrode and associated system using thermally insulated temperature sensing elements. Patent number: US Patent 5,456,682Panescu D, Fleischman SD, Whayne JG, Swanson DK, (EP Technology. Effects of temperature sensor placement on performance of temperature-controlled ablation. IEEE 17th Annual Conference, Engineering in Medicine and Biology Society, Montreal, Canada (1995)BLOUIN, L. T., MARCUS, F. I., & LAMPE, L. (1991). Assessment of Effects of a Radiofrequency Energy Field and Thermistor Location in an Electrode Catheter on the Accuracy of Temperature Measurement. Pacing and Clinical Electrophysiology, 14(5), 807-813. doi:10.1111/j.1540-8159.1991.tb04111.xBerjano, E. J. (2006). BioMedical Engineering OnLine, 5(1), 24. doi:10.1186/1475-925x-5-24Bhavaraju, N. C., Cao, H., Yuan, D. Y., Valvano, J. W., & Webster, J. G. (2001). Measurement of directional thermal properties of biomaterials. IEEE Transactions on Biomedical Engineering, 48(2), 261-267. doi:10.1109/10.909647Hong Cao, Tungjitkusolmun, S., Young Bin Choy, Jang-Zern Tsai, Vorperian, V. R., & Webster, J. G. (2002). Using electrical impedance to predict catheter-endocardial contact during RF cardiac ablation. IEEE Transactions on Biomedical Engineering, 49(3), 247-253. doi:10.1109/10.983459PETERSEN, H. H., & SVENDSEN, J. H. (2003). Can Lesion Size During Radiofrequency Ablation Be Predicted By the Temperature Rise to a Low Power Test Pulse in Vitro? Pacing and Clinical Electrophysiology, 26(8), 1653-1659. doi:10.1046/j.1460-9592.2003.t01-1-00248.xLANGBERG, J. J., LEE, M. A., CHIN, M. C., & ROSENQVIST, M. (1990). Radiofrequency Catheter Ablation: The Effect of Electrode Size on Lesion Volume In Vivo. Pacing and Clinical Electrophysiology, 13(10), 1242-1248. doi:10.1111/j.1540-8159.1990.tb02022.

Patients' preference for exercise setting and its influence on the health benefits gained from exercise-based cardiac rehabilitation

OBJECTIVE: To assess patient preference for exercise setting and examine if choice of setting influences the long-term health benefit of exercise-based cardiac rehabilitation. METHODS: Patients participating in a randomised controlled trial following either heart valve surgery, or radiofrequency ablation for atrial fibrillation were given the choice to perform a 12-week exercise programme in either a supervised centre-based, or a self-management home-based setting. Exercise capacity and physical and mental health outcomes were assessed for up to 24months after hospital discharge. Outcomes between settings were compared using a time×setting interaction using a mixed effects regression model. RESULTS: Across the 158 included patients, an equivalent proportion preferred to undertake exercise rehabilitation in a centre-based setting (55%, 95% CI: 45% to 63%) compared to a home-based setting (45%, 95% CI: 37% to 53%, p=0.233). At baseline, those who preferred a home-based setting reported better physical health (mean difference in physical component score: 5.0, 95% CI 2.3 to 7.4; p=0.001) and higher exercise capacity (mean between group difference 15.9watts, 95% CI 3.7 to 28.1; p=0.011). With the exception of the depression score in the Hospital Anxiety and Depression Score (F(3.65), p=0.004), there was no evidence of a significant difference in outcomes between settings. CONCLUSION: The preference of patients to participate in home-based and centre-based exercise programmes appears to be equivalent and provides similar health benefits. Whilst these findings support that patients should be given the choice between exercise-settings when initiating cardiac rehabilitation, further confirmatory evidence is needed

A Time-Domain Analysis of Intracardiac Electrograms for Arrhythmia Detection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73045/1/j.1540-8159.1991.tb05116.x.pd

Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans

Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 Ϯ 1 years (mean Ϯ SEM), BMI 27 Ϯ 1] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection. Simultaneously, interstitial peritendinous (IGF-I) and [procollagen type I N-terminal propeptide (PINP)], as a marker for type I collagen synthesis, were determined by microdialysis technique. Tendon collagen FSR and PINP were significantly higher in the IGF-I leg compared with the control leg (P &lt; 0.05). In conclusion, local IGF-I administration can directly enhance tendon collagen synthesis both within and around the human tendon tissue

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries