Changing health behaviors to improve health outcomes after angioplasty: a randomized trial of net present value versus future value risk communication.

Patients who have undergone angioplasty experience difficulty modifying at-risk behaviors for subsequent cardiac events. The purpose of this study was to test whether an innovative approach to framing of risk, based on 'net present value' economic theory, would be more effective in behavioral intervention than the standard 'future value approach' in reducing cardiovascular morbidity and mortality following angioplasty. At baseline, all patients completed a health assessment, received an individualized risk profile and selected risk factors for modification. The intervention randomized patients into two varying methods for illustrating positive effects of behavior change. For the experimental group, each selected risk factor was assigned a numeric biologic age (the net present value) that approximated the relative potential to improve current health status and quality of life when modifying that risk factor. In the control group, risk reduction was framed as the value of preventing future health problems. Ninety-four percent of patients completed 2-year follow-up. There was no difference between the rates of death, stroke, myocardial infarction, Class II-IV angina or severe ischemia (on non-invasive testing) between the net present value group and the future value group. Our results show that a net present risk communication intervention did not result in significant differences in health outcomes.

Non-invasive observation of repeated adenoviral GFP gene delivery to the anterior segment of the monkey eye in vivo.

BACKGROUND: Glaucoma is a group of chronic eye diseases often associated with an elevated intraocular pressure (IOP). If not controlled, the condition leads to blindness. The eye tissue responsible for maintaining aqueous humor resistance and thus normal IOP is the trabecular meshwork (TM). Adenoviral vectors are capable of transducing the TM in several rodent species. Because of the relevance of the non-human primate model in the study of glaucoma, gene transfer to the eyes of cynomolgus monkeys was investigated. METHODS: Four cynomolgus monkeys were injected with AdenoGFP into the anterior chamber: two monkeys received 10(9) pfu and the other two 10(7) pfu. One monkey received four consecutive injections into the same eye (10(7) pfu in each injection) over a 7-month period. In vivo gene transfer (fluorescence) and IOP were evaluated by standard clinical ophthalmic instruments (slit lamp biomicroscopy, gonioscopy and tonometry). Histopathology and cellular distribution were assessed postmortem. RESULTS: The first injection of the lower viral dose resulted in marked TM-preferred gene transfer visible non-invasively by in vivo gonioscopy. The expression of the transgene lasted for 3-4 weeks with little or no signs of clinical inflammation. Gene transfer was achieved on three sequential occasions (3-4 weeks each) but failed and induced substantial, albeit reversible, corneal abnormalities on the fourth occasion. CONCLUSIONS: Gene transfer to the TM and cornea can be monitored non-invasively in non-human primates, allowing correlation of gene transfer with physiological parameters. Because of ocular immune privilege, repeated anterior chamber administrations of adenoviral vectors expressing appropriate genes may have therapeutic potential for glaucoma.

What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 micromol/L.

High levels of plasma homocyst(e)ine (H[e]) are associated with increased vascular risk. Treatment is being contemplated, but the level at which patients should be treated is not known. We compared the response of carotid plaque to vitamin therapy in patients with H(e) above and below 14 micromol/L, a level commonly regarded as high enough to warrant treatment. Two-dimensional B-mode ultrasound measurement of carotid plaque was used to assess the response to vitamin therapy with folic acid 2.5 mg, pyridoxine 25 mg, and cyanocobalamin 250 microg daily, in 101 patients with vascular disease (51 with initial plasma levels above, and 50 below 14 micromol/L). Among patients with plasma H(e) >14 micromol/L, the rate of progression of plaque area was 0.21 +/- 0.41 cm2/year before vitamin therapy, and -0.049 +/- 0.24 cm2/year after vitamin therapy (P2 = .0001; paired t test). Among patients with levels <14 micromol/L, the rate of progression of plaque was 0.13 +/- 0.24 cm2/year before vitamin therapy and -0.024 +/- 0.29 cm2/year after vitamin therapy (P2 = .022, paired t test). The change in rate of progression was -0.15 +/- .44 cm2/year below 14 micromol/L, and -0.265 +/- 0.46 cm2/year above 14 micromol/L (P = 0.20). Vitamin therapy regresses carotid plaque in patients with H(e) levels both above and below 14 micromol/L. These observations support a causal relationship between homocyst(e)ine and atherosclerosis and, taken with epidemiologic evidence, suggest that in patients with vascular disease, the level to treat may be <9 micromol/L.

Predictors and outcomes of cardiac complications following elective coronary bypass grafting.

Our objective was to determine the predictors of cardiac complications among a cohort of elective coronary artery bypass graft (CABG) surgery patients and to determine the relationship of such complications to subsequent quality of life and symptoms. A total of 248 patients were enrolled and 237 completed 6 month follow-up. The combined rate of both major and minor cardiac complications was 9.7% (n = 24). Patients in this study were evaluated preoperatively, monitored intraoperatively, followed immediately postoperatively and at 6 months. Major cardiac complications accounted for 3.6% (n = 9) and minor complications for 6% (n = 15). Using multivariable logistic regression analysis, the predictors of major cardiac complications were receiving diuretics preoperatively (p = .01) and increased time during cross-clamping (p = .006). At 6 months after surgery, 19% of the patients with postoperative cardiac complications experienced worsening of symptoms, in contrast to only 8% of those without cardiac complications (p = .03). We concluded that patients who were on preoperative diuretics and those who had longer cross-clamp times were at higher risk of cardiac complications. The majority of patients who had acute cardiac complications had improved function and symptoms at 6 months postoperatively.

Depressive symptomatology in coronary artery bypass graft surgery patients.

Depression is commonly reported in coronary artery bypass graft (CABG) surgery patients. This study assesses the relationship of preoperative characteristics, life stressors, social support, major cardiac and neurologic outcomes and other complications to depressive symptomatology. Demographic and clinical data, CES-D score and information on life stressors and social support were collected from 237 patients; 92% completed 6-month follow-up. CES-D score > or = 16 was defined as significant depressive symptomatology. Significant depressive symptomatology was found in 43% of patients preoperatively and 23% postoperatively. In multivariate models, low social support (p = 0.008), presence of at least one life stressor within a year of surgery (p = 0.006), moderate to severe dyspnea (p = 0.003), little to no available help (p = 0.05) and less education (p = 0.05) were associated with higher preoperative CES-D score, while longer intensive care unit (ICU) stay (p = 0.0001) and little or no available help (p = 0.0008) predicted higher postoperative CES-D scores when controlling for preoperative CES-D scores. Neither pre- nor postoperative depressive symptomatology was related to major outcomes or other complications. A high rate of significant depressive symptomatology exists in CABG patients preoperatively, and it decreases significantly postoperatively. Patients with the above preoperative characteristics as well as those who stay in the ICU postoperatively for more than 2 days might benefit from psychosocial interventions.

[The mechanical fundus perfusion model: blood flow velocity determined by ICG angiography and Heidelberg retina flowmetry]. / Mechanisches Fundusperfusions-Modell: Blutflussgeschwindigkeiten ermittelt durch ICG-Angiographie und Heidelberg Retina Flowmetry.

BACKGROUND: Heidelberg Retina Flowmetry (HRF) is now popularly, perhaps even indiscriminately applied in eye research, without apparent concern for the fact that the results are given numerically, but without physical units. METHODS: 1) HRF: To challenge the HRF-device with known values of blood-flow velocity, a perfusion chamber with input and output connections was constructed of acrylic plastic. Three serial segments were milled to provide cross-sectional areas (1.93 mm2, 3.33 mm2, and 5.08 mm2) and accordingly decreasing, true, clinically representative flow-velocity values. Under a constant perfusion setting of a calibrated clinical infusion pump (Perfusor Secura FT, B. Braun Medical AG, Sempach, CH), heparinized human blood (P. H.) was pumped through the chamber, and the HRF-parameter, "VELOCITY" was measured within one image encompassing the three chamber segments, using a 20 degrees x 5 degrees-field and a 20 x 20-pixel measuring "window". 2) HRA: Immediately thereafter, our perfusion model was placed in front of the Heidelberg Retina Angiography device, the infusion pump started at the same constant level, and a 1 cc bolus of ICG dye was added to the blood. Digital ICG-angiography was then conducted, and the images analyzed on-screen. RESULTS: In the three segments of the perfusion chamber, flow velocities determined ICG-angiographically were 11.5 mm/s, 6.7 mm/s, and 4.4 mm/s, respectively. The corresponding values for HRF- "VELOCITY" were 5.3, 4.2, and 3.4, respectively (no units). CONCLUSIONS: Under identical perfusion conditions, the phenomenologically (ICG-angiographically) determined values of flow velocity in the 3 perfusion chamber segments ran similar to (but not numerically coincidental with) those determined for HRF-parameter "VELOCITY". Extrapolation of HRF-values to true physical units is, thus, feasible.

Development, implementation, and evaluation of a ketoconazole practice guideline for ARDS prophylaxis.

PURPOSE: The purpose of this study was to develop, implement, and evaluate a practice guideline using ketoconazole for the prevention of the adult respiratory distress syndrome (ARDS) in critically ill patients. MATERIALS AND METHODS: In hospital A (study hospital), we developed a guideline for ketoconazole prophylaxis in patients at high risk of ARDS using evidence from two randomized trials. We prospectively implemented the guideline using intensive care unit (ICU) teaching sessions, in-services, informational posters, and patient-specific individual audit and feedback. ICU caregivers in hospital B (concurrent control hospital) did not participate in the guideline development or implementation and were unaware of the conduct of the study. RESULTS: Patients at risk of ARDS were similar in hospitals A and B. Implementation of the guideline was associated with a significantly higher use of ketoconazole use for ARDS prevention (P < .0001) and a significantly lower rate of ARDS (P < .05) in hospital A compared with hospital B. Mortality, duration of ventilation, and ICU stay were similar. CONCLUSION: Development and implementation of a prophylactic ketoconazole practice guideline for ICU patients at high risk of ARDS was associated with a higher prescription of ketoconazole and a lower rate of ARDS in the study hospital than in the control hospital.

The efficacy and safety of a pharmacologic protocol for maintaining coronary artery bypass patients at a higher mean arterial pressure during cardiopulmonary bypass.

A recent randomized trial of higher versus lower mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) showed that higher MAP on CPB was associated with a lower incidence of overall cardiac and neurologic morbidity and mortality in coronary artery bypass graft surgery (CABG) patients. Cardiopulmonary bypass MAP was controlled pharmacologically while CPB flow was held constant for any given period. The objective of the present study was to assess the efficacy and safety of this pharmacologic protocol. Two hundred forty-eight patients participated in the study; the mean age was 65.8 +/- 9.4 years, 20% were women, and the mean preoperative ejection fraction was 48%. The low-flow corrected CPB MAP attained for the low and high MAP groups was 56.7 +/- 5.0 mmHg and 77.7 +/- 7.1 mmHg, respectively (p = 0.0001). Major cardiac and neurologic outcomes, postoperative blood loss, renal dysfunction, intensive care unit (ICU) stay, and duration of intubation were not found to be significantly associated with any drug in the pharmacologic protocol. These findings support that the pharmacologic protocol used to maintain CABG patients at higher MAP on CPB is both efficacious and safe.

Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.

Macrophages and chronic renal allograft nephropathy.

In a previous study we demonstrated that macrophage infiltrates stained for thromboxane A synthase (TxAS) correlated inversely with renal function six months after biopsy. We propose that macrophage based inflammation is a cofactor leading to chronic allograft nephropathy. For this study we compared four indices of renal allograft nephropathy with renal survival. The Banff Score of Inflammatory Changes (BSI) is an index of acute inflammation. The Banff Chronic Index (BCI) and Chronic Allograft Damage Index (CADI) are indexes of chronic disease. The Macrophage Index (MI) is the same as the BSI applied only to macrophages. These indices were determined on renal allograft biopsies obtained because of delayed graft function within the first week of transplantation, and for increasing plasma creatinine levels after stable function. All four indices predicted renal survival in the post-biopsy interval. MI predicted renal survival for the entire transplant period. In addition, the presence of TxAS transcripts in the renal allografts was determined using a reverse transcription-polymerase chain reaction-based assay. This confirms previous observations of TxAS in the grafts. This study supports the hypothesis that macrophage derived inflammation is a cofactor for chronic allograft nephropathy.

Severity of aortic atheromatous disease diagnosed by transesophageal echocardiography predicts stroke and other outcomes associated with coronary artery surgery: a prospective study.

Advanced atheromatous disease of the thoracic aorta identified by transesophageal echocardiography (TEE) is a major risk factor for perioperative stroke. This study investigated whether varying degrees of atherosclerosis of the descending aorta, as assessed by TEE, are an independent predictor of cardiac and neurologic outcome in patients undergoing coronary artery bypass grafting (CABG). Intraoperative TEE of the descending aorta was performed on 189 of 248 patients participating in a randomized controlled trial of low (50-60 mm Hg) or high (80-100 mm Hg) mean arterial pressure during cardiopulmonary bypass for elective CABG. Aortic atheromatous disease was graded from I to V in order of increasing severity by observers blinded to outcome. Measured outcomes were death, stroke, and major cardiac events assessed at 1 wk and 6 mo. Nine of the 189 patients with TEE examinations had perioperative strokes by 1 wk. At 1 wk, no strokes had occurred in the 123 patients with atheroma Grades I or II, while the 1-wk stroke rate was 5.5% (2/36), 10.5% (2/19), and 45.5% (5/11) for Grades III, IV, and V, respectively (Fisher's exact test, P = 0.00001). For 6-mo outcome, advancing aortic atheroma grade was a univariate predictor of stroke (P = 0.00001) and death (P = 0.03). By 6 mo there were one additional stroke, three additional deaths, and one additional major cardiac event. Atheromatous disease of the descending aorta was a strong predictor of stroke and death after CABG. TEE determination of atheroma grade is a critical element in the management of patients undergoing CABG surgery.

Measurement of organochlorine levels in postprandial serum or in blood collected in serum separator tubes.

Whether organochlorine blood levels in fasting and postprandial specimens provide equivalent measures of exposure and the extent to which collecting blood in tubes containing material to separate serum and blood cells corrupts the specimen are unclear. In this paper, we present data from two studies that address both of these issues. In the first study, 27 women provided fasting blood in plain, silicone-coated Vacutainer tubes (red-topped) and in similar tubes containing serum separator gel (SSTs), as well as a postprandial specimen in a red-topped tube. The specimens collected in SSTs were left to stand overnight, with the gel in contact with the sample. In the second study, the blood of 12 industrial incinerator workers was collected in red-topped tubes and in SSTs. Blood in SSTs was left in contact with the gel for 5 days. Serum organochlorine residue levels ([1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] (DDE)) and polychlorinated biphenyls) in samples collected in red-topped tubes were highly correlated with levels measured in samples collected in SSTs (all Pearson r values were > or = 0.79). Postprandial and fasting organochlorine levels were also highly correlated (Pearson r values > or = 0.89). Our results indicate that timing of the collection of blood in relation to meals and use of SSTs to collect blood specimens did not greatly affect the relative classification of subjects with respect to serum level of DDE or polychlorinated biphenyls. The longer the specimen was in contact with the SST gel, however, the lower the level of organochlorine that was detected and, at least for DDE, the greater the misclassification caused.

Cimetidine or ranitidine in renal transplant patients receiving cyclosporine.

While H2-receptor antagonists are commonly used in renal transplant patients to prevent peptic ulcer disease, they have been associated with immunostimulation, interference with cyclosporine (CsA) metabolism, and inhibition of tubular secretion of creatinine. In renal transplant patients, cimetidine in high doses has been shown to cause a sustained rise in serum creatinine (SCr) and to reduce creatinine clearance (CrCl) with no change in inulin clearance. In this short-term prospective study, we evaluated the effects of single daily doses of cimetidine or ranitidine on renal function, and CsA serum concentration. Fourteen renal transplant patients with stable renal function were assigned to receive either cimetidine 400 mg daily or ranitidine 150 mg daily for 7 days. In patients who received cimetidine, a slight rise in SCr was observed at days 2 and 5 which was not statistically significant, but no significant change in CsA trough level was noted. No changes in SCr or CsA level were noted in the patients who received ranitidine. No changes in GFR were observed in either cimetidine- or ranitidine-treated patients. We conclude that, in our short-term study, cimetidine or ranitidine in the doses used in this study did not affect the GFR or CsA level, or SCr.