Efficacy of combined local mechanical vibrations, continuous passive motion and thermotherapy in the management of osteoarthritis of the knee.

OBJECTIVES: We evaluated the efficacy of combined mechanical vibrations, continuous passive motion (CPM) and heat on the severity of pain in management of osteoarthritis of the knee (OA-K). METHODS: In this controlled, double crossover study, 71 OA-K patients were randomized in Phase 1 to receive 4 weeks active treatment consisting of two 20-min sessions per day (34 patients, Group AB) or treatment with a sham device (37 patients, Group BA). This was followed by a 2-week washout period (Phase 2). In Phase 3, patients crossed over so that Group AB was treated with the sham device and Group BA received active treatment for an additional 4 weeks. Patient assessments of pain (visual analog scale, VAS) and Western Ontario and McMaster Universities (WOMAC) OA index were performed at baseline and at study weeks 2, 4, 6, and 10. Net treatment effects were estimated by comparing outcomes between active and sham treatment study phases. RESULTS: Treatment benefits were noted for both of the trial's two pre-specified primary endpoints, VAS and WOMAC. VAS was reduced at all follow-up time points for patients receiving active treatment compared to sham treatment with a net treatment effect of 14.4+/-4.1 mm (P=0.001). Similarly, the WOMAC score was reduced significantly with active treatment at all measured points with a net effect of 8.8+/-1.9 points (P<0.001). The secondary endpoints, range of motion (ROM) and treatment satisfaction, also improved with active vs sham treatment. CONCLUSION: Four weeks treatment with combined CPM, vibration and local heating significantly decreases pain, improves ROM and the quality of life in patients with OA-K (ClinicalTrials.gov registration number: NCT00858416).

Cost-effectiveness analysis of long-term moderate exercise training in chronic heart failure.

The purpose of this study is to perform a cost-effectiveness analysis of long-term moderate exercise training (ET) in patients with stable chronic heart failure. In particular, the study focuses on the survival analysis and cost savings from the reduction in the hospitalization rate in the exercise group. In the past 10 years, ET has been shown to be beneficial for patients with stable class II and III heart failure in many randomized clinical trials. However, the cost-effectiveness of a long-term ET program has not been addressed for outcomes related to morbidity/mortality end points or health care utilization. We examined the cost-effectiveness of a 14-month long-term training in patients with stable chronic heart failure. The estimated increment cost for the training group, $3,227/patient, was calculated by subtracting the averted hospitalization cost, $1,336/patient, from the cost of ET and wage lost due to ET, estimated at $4,563/patient. For patients receiving ET, the estimated increment in life expectancy was 1.82 years/person in a time period of 15.5 years, compared with patients in the control group. The cost-effectiveness ratio for long-term ET in patients with stable heart failure was thus determined at $1,773/life-year saved, at a 3% discount rate. Long-term ET in patients with stable chronic heart failure is cost-effective and prolongs survival by an additional 1.82 years at a low cost of $1,773 per/life-year saved.

Preoperative and intraoperative predictors of postoperative morbidity, poor graft function, and early rejection in 190 patients undergoing liver transplantation.

HYPOTHESIS: Preoperative and intraoperative variables predict in part adverse outcome after liver transplantation. DESIGN: Prospective, blinded, cohort study. SETTING: Tertiary care hospital. SUBJECTS: A total of 190 adult patients undergoing primary liver transplantation. MAIN OUTCOME MEASURE: Adverse outcome was prospectively defined as either in-hospital death or prolonged postoperative hospitalization (>14 days) associated with morbidity. Potential preoperative and intraoperative risk factors were collected. Associations were tested by univariate analysis followed by multivariate analysis in which preoperative factors were entered before intraoperative factors. RESULTS: Adverse outcome occurred in 44.7% of patients. Incidences of other complications were as follows: in-hospital mortality (8.4%), primary graft nonfunction (4.2%), poor early graft function (1.1%), and early rejection (31.2%). Univariate predictors of adverse outcome were United Network for Organ Sharing status (P =.003), Child-Turcotte-Pugh score (P =.02), POSSUM physiological score (P =.002), recipient age (P =.01), preoperative serum high-density lipoprotein cholesterol level (P =.03), preoperative serum creatinine level (P =.002), preoperative serum total IgG level (P =.004), duration in hospital preoperatively (P =.03), operative duration (P<.001), allogeneic erythrocyte transfusions (P<.001), total intraoperative fluids (P =.002), and use of inotropic agents (P =.01). In the final multivariate model, predictors of adverse outcome were United Network for Organ Sharing status (P =.03), recipient age (P =.002), and total intraoperative fluids (P =.04). Most patients who died or had a prolonged hospitalization exhibited dysfunction of more than 1 organ system, including pulmonary, renal, and infectious complications. CONCLUSIONS: Adverse outcome occurs frequently after liver transplantation, usually involves multiple organ systems, and is predicted in part by several preoperative and intraoperative factors.

Essential tremor: occupational exposures to manganese and organic solvents.

Occupational exposures to manganese and organic solvents cause parkinsonism as well as prominent action tremor, resembling essential tremor (ET), yet their association with ET has not been studied. These chemicals cause cerebellar pathology. Cerebellar changes have been linked with ET. Using lifetime occupational histories, the authors demonstrated that occupational exposures were similar in cases and controls, which does not support an etiologic link between occupational exposures to these chemicals and ET.

Upright posture and postprandial hypotension in elderly persons.

BACKGROUND: Syncope and falls are common in elderly persons and often result from the interaction of multiple clinical abnormalities. Both orthostatic hypotension and postprandial hypotension increase in prevalence with age. OBJECTIVE: To determine whether meal ingestion enhances orthostatic hypotension in elderly persons. DESIGN: Controlled paired comparison. SETTING: Clinical research center. PATIENTS: 50 functionally independent elderly persons recruited from local senior centers (n = 47) and from patients hospitalized with an unexplained fall or syncope (n = 3) (mean age, 78 years [range, 61 to 96 years]). Twenty-five participants (50%) were taking antihypertensive medication. MEASUREMENTS: Sequential head-up tilt-table testing at 60 degrees was performed before and 30 minutes after ingestion of a standardized warm liquid meal that was high in carbohydrates. Heart rate and blood pressure were continuously monitored. RESULTS: Meal ingestion (P < 0.01) and time spent upright (P < 0.001) were significantly associated with systolic blood pressure, but no significant interaction was found between meal ingestion and time spent upright (P > 0.2). These findings suggest that the association between meal ingestion and head-up tilt-table testing were additive and not synergistic. However, the proportion of participants with symptomatic hypotension increased during head-up tilt-table testing after meal ingestion (12% during preprandial testing and 22% during postprandial testing). Symptomatic hypotension tended to occur more often and sooner after meal ingestion than before meal ingestion (P = 0.03). CONCLUSIONS: Meal ingestion and head-up tilt-table testing are associated with increasing occurrences of symptomatic hypotension. After meal ingestion and head-up tilt-table testing, 22% of functionally independent elderly persons had symptomatic hypotension.

Arterial and venous Thrombelastograph variables differ during cardiac surgery.

UNLABELLED: The Thrombelastograph (TEG; Haemoscope Corp., Skokie, IL) coagulation analyzer is an effective point-of-care monitor for routine clinical practice and clinical research. Prior investigators have used either arterial or venous samples of blood for TEG measurements. We conducted this prospective cohort study to determine potential differences in TEG variables between arterial and venous blood samples. Arterial and venous samples were drawn from 40 cardiac surgical patients, yielding 134 pairs for comparison. Twenty-nine comparisons (control) were between arterial and arterial samples and were not significantly different. For the arterial and venous comparisons (n = 105), mean (+/-sd) arterial and venous values were the following: reaction time, 10 +/- 2 mm vs 13 +/- 4 mm, P = 0.004; maximum amplitude, 59 +/- 9 mm vs 49 +/- 12 mm, P < 0.001; alpha angle, 61 +/- 10 degrees vs 51 +/- 14 degrees, P < 0.001; K, 5 +/- 2 mm vs 8 +/- 4 mm, P = 0.007; and lysis, 2.5 +/- 1.7 vs 2.5 +/- 2.0 (not significant), arterial versus venous, respectively. Arterial blood samples demonstrated TEG values reflecting stronger (larger maximum amplitude) and faster (shorter reaction time and K value, wider alpha angle) clot formation. The results suggest that users of TEG coagulation analyzers should be consistent with the site of blood sampling given the potential differences obtained. IMPLICATIONS: Thrombelastograph (TEG) values obtained from venous blood samples differ from values obtained from arterial blood samples. When the TEG coagulation analyzer is used for clinical purposes, it is important to be consistent in the blood collection site.

Changes in sample size and length of follow-up to maintain power in the coronary artery bypass graft (CABG) patch trial.

The CABG Patch Trial is testing the hypothesis that prophylactic use of implantable cardiac defibrillators (ICDs) will improve survival in high-risk coronary heart disease patients undergoing CABG surgery. The original design called for 800 patients to be randomized to ICD prophylaxis or to no therapy and followed for 2 to 6.5 years (average, 40 months) to a common termination date. Since the ICD pulse generators used in this trial lasted about 42 months, the original design required ICD replacement in many patients. At its first two meetings in 1993, the Data and Safety Monitoring Board (DSMB) formalized a plan to adjust sample size in October 1994 if the control group mortality rate was lower than expected. In June 1994, an unanticipated and unique event--a subpoena from the Office of the Inspector General (OIG)--made it impossible to replace about half of the ICD generators and threatened to shorten follow-up substantially. If follow-up had been stopped on the date originally planned, but without replacing ICDs, the average follow-up would have fallen from 40 months to about 33 months. Also, in October 1994, the control group mortality rate was found to be somewhat lower than expected. Together, the abbreviated follow-up and lower control group mortality threatened to reduce power substantially. The DSMB reviewed several options for restoring power. Because mortality rates in the first month after CABG surgery were about seven times as high as thereafter and because ICD therapy did not reduce surgical mortality (death during the first 30 days), extending the follow-up benefits power more than does increasing the sample size. However, the limit on extending follow-up was 42 months (the expected battery life of the ICD). Data from the ICD-treated group was not reviewed or considered in making the decision. After reviewing many options for restoring power, the DSMB recommended that the sample size be increased from 800 to 900 patients and that almost all patients be followed for 42 months. This recommendation extended follow-up for 2 years beyond the original termination date planned for the trial and dictated that patients close out after 42 months rather than on a common termination date.

Quality-of-life six months after CABG surgery in patients randomized to ICD versus no ICD therapy: findings from the CABG Patch Trial.

UNLABELLED: ICDs can affect a patient's perceived quality-of-life (QOL). This article describes the QOL in patients who participated in The CABG Patch Trial. This trial evaluated the potential benefit of empiric ICD implantation in patients with an increased risk of arrhythmic cardiac death as determined by reduced ejection fraction (<0.36) and an abnormal signal-averaged ECG. Patients were randomized to control (no ICD) or treatment (ICD) limbs. QOL was measured using the SF-36 and other measures among 490 (68%) of 719 patients available at 6-month follow-up. Analysis was performed on 228 control patients (those without ICDs) and 262 patients with ICDs. RESULTS: Six months after having CABG surgery, patients in the ICD group had lower levels of psychological well-being than those in the control group. In addition, compared to controls, patients whose ICDs had delivered therapy reported feeling less healthy, had reduced physical and emotional role functioning, and had lower levels of psychological well-being. CONCLUSION: Strategies aimed at easing patients' adjustment to ICDs should be developed and tested for efficacy in the setting of ICD prophylaxis.

Baseline characteristics of patients in the coronary artery bypass graft (CABG) Patch Trial.

BACKGROUND: Patients with left ventricular dysfunction who undergo coronary artery bypass graft (CABG) surgery frequently have late sudden cardiac death. The CABG Patch Trial is a prospective, randomized, multicenter clinical trial that randomized patients at high risk at the completion of CABG surgery to implantation of an epicardial implantable cardioverter defibrillator (ICD) or to no antiarrhythmic treatment. The trial was designed to determine whether prophylactic implantation of an ICD at the time of CABG surgery would result in a lower total mortality in long-term follow-up. METHODS: Patients undergoing CABG surgery were eligible for the trial if they were younger than 80 years, had a left ventricular ejection fraction less than 0.36, and had an abnormal signal averaged electrocardiogram. Patients with a history of sustained ventricular tachycardia or ventricular fibrillation were excluded from the trial. All patients were scheduled to undergo follow-up at 3-month intervals until 42 months after surgery. RESULTS: Randomization of patients in the trial ended in February 1996. During the recruitment period 71,855 patients were screened, 1,422 were eligible, 1,055 were enrolled (signed consent forms), and 900 patients (76% of eligible patients) were randomized. The mean age of the 446 patients in the ICD group was 64 years versus 63 years for the 454 patients in the control group. A total of 87% of the participants in the ICD group were men versus 82% in the control group (p = NS). Most of the patients had a history of hypertension (55%), smoking (78%), and hypercholesterolemia (54%). Half of the patients had clinical heart failure, and the mean ejection fraction for both patient groups was 0.27 +/- 0.06. No difference was seen in the history of myocardial infarction (83%), congestive heart failure (50%), or atrial (11%) or ventricular (17%) arrhythmias between the two groups. Major clinical characteristics (age, sex, number of previous infarctions, incidence of heart failure, and mean left ventricular ejection fraction) were almost identical to those found in another ICD primary prevention trial, the Multicenter Automatic Defibrillator Implantation Trial (MADIT). CONCLUSIONS: A high risk sample of patients was enrolled in The CABG Patch Trial, as shown by examination of their baseline characteristics.

Erythrocyte 3-O-methyl-D-glucose uptake assay for diagnosis of glucose-transporter-protein syndrome.

Glucose transport into the brain is mediated by a facilitative glucose-transporter protein, GLUT-1. A GLUT-1 defect results in the Glucose-Transporter-Protein Syndrome (GTPS), characterized by infantile epilepsy, developmental delay, and acquired microcephaly. The diagnosis is currently based on clinical features, low to normal lactate levels and low glucose levels (hypoglycorrhachia) in the cerebrospinal fluid, and the demonstration of impaired GLUT-1 function in erythrocytes as described here. Blood samples were collected in sodium-heparin or citrate-phosphate-dextrose solution and uptake of 14C-labeled 3-O-Methyl-D-glucose (3OMG into erythrocytes (0.5 mmol/L 3OMG; 1 microCi/mL) was measured at 4C and pH 7.4. Three-OMG influx was terminated at 5-second intervals, washed cells were lysed, and uptake was quantitated by liquid scintillation counting. Patients' uptake (n = 22) was 44 +/- 8% of controls (100 +/- 22%, n = 70). Statistical analyses showed an uptake cut-off point at 60% uptake, a sensitivity of 86% (95%-confidence interval 78 to 94%), and a specificity of 97% (95%-confidence interval 93 to 100%). Gender, age, and ketosis did not influence 3OMG uptake. This assay provides a reproducible and accurate laboratory test for diagnosing the GTPS.

Saphenous vein biopsy: a predictor of vein graft failure.

PURPOSE: To determine why some vein grafts fail, we prospectively studied the relationship between the histologic condition of the greater saphenous vein (GSV) at the time of grafting and subsequent stenosis of the vein graft. METHODS: Ninety-four remnant segments of GSVs were obtained at the time of infrainguinal bypass in 91 patients and were perfusion fixed before histologic and ultrastructural examination. All bypass grafts were evaluated clinically and by duplex ultrasonography at regular intervals from 1 to 30 months after operation. All 24 grafts that developed lesions that caused thrombosis (failed grafts) or flow reduction (failing grafts) underwent arteriography and appropriate operative or other interventional correction of the causative lesion. RESULTS: There was no significant difference in the incidence of coronary artery disease, kidney disease, hypertension, or history of smoking in patients with normally functioning and failed or failing grafts. Diabetes occurred with an increased frequency in failed or failing grafts (p = 0.056). At the time of their insertion, GSVs that subsequently developed significant lesions had thicker walls (0.72 +/- 0.33 mm) compared with normally functioning grafts (0.58 +/- 21 mm; p < 0.02). Most of this difference was related to a significantly thicker intima (0.27 +/- 0.17 vs 0.11 +/- 0.7 mm; p < 0.0001). Another significant finding was the presence of subendothelial spindle-shaped cells greater than five cell layers thick. This occurred more often in pregraft biopsies from grafts that developed significant lesions (70.4% vs 7.5%, p < 0.0001). Electron microscopic examination of these cells demonstrated a subpopulation of poorly differentiated cells with few fibers and many vesicles. Four of 24 (17%) failed or failing grafts had evidence of vein wall calcification at the time of vein grafting. This was seen in only one (1.4%) of 70 normally functioning grafts without lesions (p < 0.005). CONCLUSIONS: We conclude that GSVs with thick and calcified walls or hypercellular intima at the time of grafting are at increased risk of developing intragraft lesions that may lead to graft failure. Frequent duplex ultrasonography surveillance is particularly warranted for such high-risk grafts.

Comparison of P-POSSUM risk-adjusted mortality rates after surgery between patients in the USA and the UK.

BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) criteria have been used to assess surgical risk in patients in the UK. The aim was to determine how applicable these criteria are to patients undergoing surgery in the USA. METHODS: Two cohorts of patients undergoing major non-cardiac surgery were followed prospectively in the USA (n = 1056) and the UK (n = 1539). Each patient was assigned a risk score for preoperative physiological status and operative severity using the established POSSUM criteria. Death in hospital was the primary outcome measure. For each patient a predicted risk of death was calculated from Portsmouth POSSUM (P-POSSUM) methodology using an established equation. The relationships between predicted and observed mortality rates in each cohort were investigated by means of multivariate logistic regression. RESULTS: Within each cohort, an increase in risk estimated by P-POSSUM predicted an increase in observed mortality rate (P < 0.001). For any given risk level, however, mortality rates were significantly higher in the UK cohort than in the US cohort (odds ratio 4.50 (95 per cent confidence interval 2.81 to 7.19); Z = 6.25, P < 0.001). CONCLUSION: An increase in predicted risk, based on the P-POSSUM methodology, was associated with a higher mortality rate in patients from both countries. However, risk-adjusted mortality rates following major surgery were four times higher in the UK cohort. These marked differences warrant validation in a larger number of centres.