Models,strategies, and tools

This paper presents a case for careful consideration of theory in planning to implement evidence-based practices into clinical care. As described, theory should be tightly linked to strategic planning through careful choice or creation of an implementation framework. Strategies should be linked to specific interventions and/or intervention components to be implemented, and the choice of tools should match the interventions and overall strategy, linking back to the original theory and framework. The thesis advanced is that in most studies where there is an attempt to implement planned change in clinical processes, theory is used loosely. An example of linking theory to intervention design is presented from a Mental Health Quality Enhancement Research Initiative effort to increase appropriate use of antipsychotic medication among patients with schizophrenia in the Veterans Health Administration.     

Long-term precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism.

(18)F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K(i), reflects regional bone metabolism. The aim of this study was to compare the long-term precision of (18)F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. METHODS: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent (18)F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the (18)F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K(i-4k)), a 3k 3-compartmental model using nonlinear regression analysis (K(i-3k)), Patlak analysis (K(i-PAT)), and standardized uptake values. RESULTS: With the exception of a small but significant decrease in K(i-3k) at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%-19%), 13.8% (10%-22%), 14.4% (11%-22%), and 26.6% (19%-40%) for K(i-3k), K(i-PAT), mean standardized uptake value, and K(i-4k), respectively. For comparison, the precision of the biochemical markers was 10% (7%-15%), 18% (13%-27%), and 14% (10%-21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K(i-4k) to 0.85 for K(i-3k). No significant correlation was found between the repeated mean standardized uptake value measurements. CONCLUSION: The precision and intraclass correlation observed for K(i-3k) and K(i-PAT) was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of (18)F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.     

Fatal nosocomial Legionnaires' disease: relevance of contamination of hospital water supply by temperature-dependent buoyancy-driven flow from spur pipes.

The investigation, epidemiology, and effectiveness of control procedures during an outbreak of Legionnaires'' disease involving three immunosuppressed patients are described. The source of infection appeared to be a network of fire hydrant spurs connected directly to the incoming hospital mains water supply. Removal of these hydrants considerably reduced, but failed to eliminate, contamination of water storage facilities. As an emergency control procedure the incoming mains water was chlorinated continuously. Additional modifications to improve temperature regulation and reduce stagnation also failed to eliminate the legionellae. A perspex test-rig was constructed to model the pre-existing hospital water supply and storage system. This showed that through the hydraulic mechanism known as ''temperature buoyancy'', contaminated water could be efficiently and quickly exchanged between a stagnant spur pipe and its mains supply. Contamination of hospital storage tanks from such sources has not previously been considered a risk factor for Legionnaires'' disease. We recommend that hospital water storage tanks are supplied by a dedicated mains pipe without spurs.     

Ascending Aortic Extension for Right Pulmonary Artery Stenosis Associated With Ventricular-to-Pulmonary Artery Conduit Replacement

A bstract Background : Ventricular-to-pulmonary artery conduits in growing patients with congenital heart disease will require replacement from time to time due to somatic growth, neointimal hyperplasia, and pulmonary artery stenosis. The purpose of this article is to review our experience with ascending aortic extension for significant long-segment pulmonary artery stenosis in patients undergoing reoperation for right ventricular-to-pulmonary artery conduit replacement. Methods : From 1989 to 1997, 8 patients had aortic transection, right pulmonary artery augmentation arterioplasty, and aortic interposition graft (Hemashield in 7 and Gore-tex in 1) in association with right ventricular-to-pulmonary artery conduit replacement in 7 patients and completion Fontan operation in 1 patient. Aortic cross-clamp time was 90 ± 34 minutes, and the cardiopulmonary bypass time was 205 ± 37 minutes. Results : All patients survived. In those 7 patients who had conduit replacement, the RV/LV ratio declined from 0.78 ± 0.15 to 0.45 ±; 0.05 postoperatively (P < 0.05). Average length of stay was 8.9 ± 7.2 days. Follow-up range is 18 months to 8 years (mean 4 years). Two complications included cardiac transplantation for pre-existing poor left ventricular function and accelerated conduit stenosis leading to conduit re-replacement. Conclusion : Ascending aortic extension facilitates long-segment pulmonary artery augmentation arterioplasty and enlarges the retroaortic space, preventing future compression restenosis.     

Effect of interleukin 2 on Kupffer cell activation. Interleukin 2 primes and activates Kupffer cells to suppress hepatocyte protein synthesis in vitro

Interleukin 2 (IL-2) is an essential mediator of the immune response and has also been shown to be protective in experimental models of sepsis. Macrophages have IL-2 receptors but their function is unknown. We investigated the effect of IL-2 on Kupffer cells, the fixed macrophages of the liver, using an in vitro rat hepatocyte-Kupffer cell coculture system. In this model, endotoxin (lipopolysaccharide) triggers Kupffer cells to induce suppression of hepatocyte protein synthesis. We found that pretreatment with 10 U/mL or more of IL-2 primed Kupffer cells, significantly reducing the concentration of lipopolysaccharide necessary to trigger Kupffer cell-mediated suppression of hepatocyte protein synthesis. Higher concentrations of IL-2 (greater than or equal to 1 x 10(4) U/mL) alone were capable of priming and triggering Kupffer cells to suppress hepatocyte protein synthesis. These data show that IL-2 increases Kupffer cell sensitivity to endotoxin, suggesting that IL-2 may play an important role in regulating macrophage responses to septic stimuli.     

Progesterone potentiation of bupivacaine arrhythmogenicity in pentobarbital-anesthetized rats and beating rat heart cell cultures.

The effects of progesterone treatment on bupivacaine arrhythmogenicity in beating rat heart myocyte cultures and on anesthetized rats were determined. After determining the bupivacaine AD50 (the concentration of bupivacaine that caused 50% of all beating rat heart myocyte cultures to become arrhythmic), we determined the effect of 1-hour progesterone HCl exposure on myocyte contractile rhythm. Each concentration of progesterone (6.25, 12.5, 25, and 50 micrograms/ml) caused a significant and concentration-dependent reduction in the AD50 for bupivacaine. Estradiol treatment also increased the arrhythmogenicity of bupivacaine in myocyte cultures, but was only one fourth as potent as progesterone. Neither progesterone nor estradiol effects on bupivacaine arrhythmogenicity were potentiated by epinephrine. Chronic progesterone pretreatment (5 mg/kg/day for 21 days) caused a significant increase in bupivacaine arrhythmogenicity in intact pentobarbital-anesthetized rats. There was a significant decrease in the time to onset of arrhythmia as compared with control nonprogesterone-treated rats (6.2 +/- 1.3 vs. 30.8 +/- 2.5 min, mean +/- SE). The results of this study indicate that progesterone can potentiate bupivacaine arrhythmogenicity both in vivo and in vitro. Potentiation of bupivacaine arrhythmia in myocyte cultures suggests that this effect is at least partly mediated at the myocyte level.     

Perspectives on HIV/AIDS epidemiology and prevention from the Eighth International Conference on AIDS.

The Eighth International AIDS Symposium in Amsterdam, the Netherlands, provided updated scientific and programmatic information on the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) to thousands of interested participants. As in the other scientific areas, the amount of information presented in epidemiology and prevention was overwhelming; however, the scientific progress described was steady but incremental. This commentary summarizes progress made in three selected areas that were highlighted during the meeting's scientific session and a fourth that received widespread media attention: (1) the epidemiology of HIV/AIDS in heterosexual women; (2) tuberculosis as an increasing opportunistic pathogen in HIV-infected persons; (3) prevention research, practice, and policy; and (4) preliminary reports of severe immunodeficiency in persons without evident HIV infection. In order to stem HIV transmission worldwide, a safe and effective vaccine is urgently needed. Currently, in the absence of such a vaccine, it is crucial for all of the world's communities to apply the best science-based prevention methods available.