Tumour necrosis factor-alpha potentiates CR3-induced respiratory burst by activating p38 MAP kinase in human neutrophils.

CR3 and Fc gamma Rs are the main receptors involved in the phagocytic process leading to engulfment and killing of microbes by production of reactive oxygen intermediates (ROI) and degranulation. Various inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS), are known to prime neutrophils leading to increased bactericidal responses, but the underlying mechanism of priming has only been partially elucidated. The purpose of this study was to investigate how TNF-alpha primes neutrophils for subsequent stimuli via either CR3 or Fc gamma R. The receptors were specifically activated with pansorbins (protein-A-positive Staphylococcus aureus) coated with anti-CR3, anti-Fc gamma RIIa, or anti-Fc gamma RIIIb monoclonal antibody. Activation of neutrophils with these particles resulted in ROI production as measured by chemiluminescence. Anti-CR3 pansorbins induced the most prominent ROI production in neutrophils. TNF-alpha potentiated the CR3-mediated respiratory burst but had little effect on that mediated by Fc gamma Rs. The priming effect of TNF-alpha on CR3-mediated ROI production is associated with an increased activation of p38 MAPK as well as tyrosine phosphorylation of p72(syk). Pretreatment of neutrophils with the inhibitors for p38 MAPK and p72(syk) markedly suppressed the respiratory burst induced by CR3. Furthermore, TNF-alpha induced about a three-fold increase in the expression of CR3 in neutrophils, an effect which is blocked by the p38 MAPK inhibitor. Taken together, these results showed that TNF-alpha potentiates the CR3-mediated respiratory burst in neutrophils not only by triggering a p38 MAPK-dependent up-regulation of CD11b/CD18 but also by modulating the signalling pathways.

Are patients at Veterans Affairs medical centers sicker? A comparative analysis of health status and medical resource use.

BACKGROUND: The Veterans Affairs (VA) health system has been criticized for being inefficient based on comparisons of VA care with non-VA care. Whether such comparisons are biased by differences between the VA patient population and the non-VA patient population is not known. Our objective is to determine if VA patients are different from non-VA patients in terms of health status and medical resource use. METHOD: We analyzed 128,099 records from the National Health Interview Survey for the years 1993 and 1994. We compared the VA patient population with the general patient population for self report on health status, number of medical conditions, number of outpatient physician visits, number of hospital admissions, and number of hospital days each year. RESULTS: The VA patient population had poorer health status (odds ratio [OR], 14.7; 95% confidence interval [CI], 10.7-20.2), more medical conditions (OR, 14; 95% CI, 10.5-18.7), and higher medical resource use compared with the general patient population (OR, 3.7 for 3 or more physician visits per year; OR 5.4 for 3 or more hospital admissions per year; OR, 7.7 for 21 or more days spent in a hospital per year). However, after controlling for health and sociodemographic differences, VA patients had similar resource use compared with the general patient population. CONCLUSION: Large differences in sociodemographic status, health status, and subsequent resource use exist between the VA and the general patient population. Therefore, comparisons of VA care with non-VA care need to take these differences into account. Furthermore, health care planning and resource allocation within the VA should not be based on data extrapolated from non-VA patient populations. Arch Intern Med. 2000;160:3252-3257.

Improving residents' compliance with standards of ambulatory care: results from the VA Cooperative Study on Computerized Reminders.

CONTEXT: Computerized systems to remind physicians to provide appropriate care have not been widely evaluated in large numbers of patients in multiple clinical settings. OBJECTIVE: To examine whether a computerized reminder system operating in multiple Veterans Affairs (VA) ambulatory care clinics improves resident physician compliance with standards of ambulatory care. DESIGN, SETTING, AND PARTICIPANTS: A total of 275 resident physicians at 12 VA medical centers were randomly assigned in firms or half-day clinic blocks to either a reminder group (n = 132) or a control group (n = 143). During a 17-month study period (January 31, 1995-June 30, 1996), the residents cared for 12,989 unique patients for whom at least 1 of the studied standards of care (SOC) was applicable. MAIN OUTCOME MEASURES: Compliance with 13 SOC, tracked using hospital databases and encounter forms completed by residents, compared between residents in the reminder group vs those in the control group. RESULTS: Measuring compliance as the proportion of patients in compliance with all applicable SOC by their last visit during the study period, the reminder group had statistically significantly higher rates of compliance than the control group for all standards combined (58.8% vs 53.5%; odds ratio [OR], 1.24; 95% confidence interval [CI], 1.08-1.42; P =.002) and for 5 of the 13 standards examined individually. Measuring compliance as the proportion of all visits for which care was indicated in which residents provided proper care, the reminder group also had statistically significantly higher rates of compliance than the control group for all standards combined (17.9% vs 12.2%; OR, 1.57; 95% CI, 1.45-1.71; P<.001) and for 9 of the 13 standards examined individually. The benefit of reminders, however, declined throughout the course of the study, even though the reminders remained active. CONCLUSIONS: Our data indicate that reminder systems installed at multiple sites can improve residents' compliance to multiple SOC. The benefits of such systems, however, appear to deteriorate over time. Future research needs to explore methods to better sustain the benefits of reminders. JAMA. 2000;284:1411-1416.

Understanding racial variation in the use of coronary revascularization procedures: the role of clinical factors.

BACKGROUND: Black patients undergo coronary artery bypass grafting and percutaneous transluminal coronary angioplasty less often than white patients. It is unclear how racial differences in clinical factors contribute to this variation. METHODS: A retrospective cohort study was performed of 666 male patients (326 blacks and 340 whites), admitted to 1 of 6 Veterans Affairs hospitals from October 1, 1989, to September 30, 1995, with acute myocardial infarction or unstable angina who underwent cardiac catheterization. The primary comparison was whether racial differences in percutaneous transluminal coronary angioplasty and coronary artery bypass grafting rates persisted after stratifying by clinical appropriateness of the procedure, measured by the appropriateness scale developed by the RAND Corporation, Santa Monica, Calif. RESULTS: Whites more often than blacks underwent a revascularization procedure (47% vs 28%). There was substantial variation in black-white odds ratios within different appropriateness categories. Blacks were significantly less likely to undergo percutaneous transluminal coronary angioplasty (odds ratio, 0.30; 95% confidence interval, 0.14-0.63 [P<.01]) when the indication was rated "equivocal." Similarly, blacks were less likely to undergo coronary artery bypass grafting (odds ratio, 0.44; 95% confidence interval, 0.23-0.86 [P<.01]) when only coronary artery bypass grafting was indicated as "appropriate and necessary." Differences in comorbidity or use of cigarettes or alcohol did not explain these variations. Using administrative data from the Veterans Health Administration, we found no differences in 1-year (5.2% vs 7.4%) and 5-year (23.3% vs 26.2%) mortality for blacks vs whites. CONCLUSION: Among patients with acute myocardial infarction or unstable angina, variation in clinical factors using RAND appropriateness criteria for procedures explained some, but not all, racial differences in coronary revascularization use.

CR3, FcgammaRIIA and FcgammaRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca(2+), phospholipase D and tyrosine phosphorylation.

Human neutrophils express two different types of phagocytic receptors, complement receptors (CR) and Fc receptors. In order to characterize the different signaling properties of each receptor we have used non-adherent human neutrophils and investigated CR3, FcgammaRIIA and FcgammaRIIIB for their signaling capacity. Selective activation of each receptor was achieved by coupling specific antibodies to heat-killed Staphylococcus aureus particles, Pansorbins, through their Fc moiety. Despite the fact that these particles are not phagocytosed, we show that addition of Pansorbins with anti-CD18 antibodies recognizing CR3 induced prominent signals leading to a respiratory burst. Stimulation with anti-FcgammaRIIIB Pansorbins induced about half of the response induced by anti-CR3 Pansorbins, whereas anti-FcgammaRIIA Pansorbins induced an even weaker signal. However, FcgammaRIIA induced strong phosphorylation of p72(syk) whereas FcgammaRIIIB induced only a very weak p72(syk) phosphorylation. During CR3 stimulation no tyrosine phosphorylation of p72(syk) was seen. Both phospholipase D and NADPH oxidase activities were dependent on intracellular calcium. This is in contrast to tyrosine phosphorylation of p72(syk) that occurred even in calcium-depleted cells, indicating that oxygen metabolism does not affect p72(syk) phosphorylation. Inhibitors of tyrosine phosphorylation blocked the respiratory burst induced by both FcgammaRIIA and FcgammaRIIIB as well as CR3. This shows that tyrosine phosphorylation of p72(syk) is an early signal in the cascade induced by FcgammaRIIA but not by CR3.

Screening for problem drinking: impact on physician behavior and patient drinking habits.

OBJECTIVE: To assess the effect of a screen for problem drinking on medical residents and their patients. DESIGN: Descriptive cohort study. SETTING: Veterans Affairs Medical Clinic. PATIENTS: Patients were screened 2 weeks before a scheduled visit (n = 714). Physicians were informed if their patients scored positive. MEASUREMENTS AND MAIN RESULTS: Physician discussion of alcohol use was documented through patient interview and chart review. Self-reported alcohol consumption was recorded. Of 236 current drinkers, 28% were positive for problem drinking by the Alcohol Use Disorders Identification Test (AUDIT). Of 58 positive patients contacted at 1 month, 78% recalled a discussion about alcohol use, 58% were advised to decrease drinking, and 9% were referred for treatment. In 57 positive patient charts, alcohol use was noted in 33 (58%), and a recommendation in 14 (25%). Newly identified patients had fewer notations than patients with prior alcohol problems. Overall, 6-month alcohol consumption decreased in both AUDIT-positive and AUDIT-negative patients. The proportion of positive patients who consumed more than 16 drinks per week (problem drinking) decreased from 58% to 49%. Problem drinking at 6 months was independent of physician discussion or chart notation. CONCLUSIONS: Resident physicians discussed alcohol use in a majority of patients who screened positive for alcohol problems but less often offered specific advice or treatment. Furthermore, residents were less likely to note concerns about alcohol use in charts of patients newly identified. Finally, a screen for alcohol abuse may influence patient consumption.

Appropriateness of imaging procedure requests: do radiologists agree?

OBJECTIVE: We explored the agreement among radiologists in their evaluation of the appropriateness of individual requests for imaging procedures. MATERIALS AND METHODS: We reviewed 318 noninterventional CT, sonographic, MR imaging, and nuclear medicine procedures ordered at a general internal medicine clinic during 8 months in 1995. Five subspecialty radiologists used data from the radiology request from and clinic notes to independently rate the appropriateness of each requested imaging procedure on a four-point scale. The radiologists were unaware of the results achieved by each procedure. Each case was reviewed by at least three radiologists, of whom at least one had relevant subspecialty expertise. Agreement among radiologists was analyzed using Cohen's kappa statistic and weighted kappa statistics and Cronbach's alpha statistic. RESULTS: Nonchance agreement (kappa) was .19 +/- .05; weighted kappa was .24 +/- .05. Interrater agreement was significantly greater than that expected from chance alone (p < .01). The composite score, defined as the average of the radiologists' scores for each case, showed moderate reliability, as evidenced by a value for Cronbach's alpha of 70. CONCLUSION: In the absence of explicit criteria, we found modest but statistically significant agreement among radiologists about the appropriateness of individual requests for imaging procedures. The disagreement among radiologists highlights the importance of developing well-reasoned, explicit criteria by which to judge the appropriateness of diagnostic radiology procedures. Further study is needed to elucidate the relationship between appropriateness and actual patient outcomes.

Chamber for indirect calorimetry with improved transient response.

A chamber for indirect calorimetry has been constructed that utilises previously published general equations for the calculation of respiration. Owing to the large size of the chamber, the changes in gas concentration caused by a subject are very small. Therefore, algorithms are developed for noise suppression and trend identification. Using the exact solution of the equations for steady state, each gas concentration is fitted by a least square method to two connected exponential segments, of variable length, for the preceding 30 min period. Independently of the location of the join between the two segments, the gas concentration and its time derivative are evaluated at -15 min. This process is repeated, and its results are presented once every minute. As proven by gas injection tests, this procedure gives an instantaneous response to a single change in respiration, a correct averaging of repeated changes in respiration with periods of less than 15 min and noise suppression. It is concluded that this chamber is useful not only for traditional 24 h energy expenditure measurements, but also for experiments requiring rapid responses.

Outpatient internal medicine preoperative evaluation: a randomized clinical trial.

The purpose of this study was to evaluate the effect on resource use of a program outpatient internal medicine preoperative evaluation in a two arm parallel design randomized clinical trial. In a tertiary care teaching Veterans Affairs hospital, 355 patients (179 inpatient arm, 176 outpatient arm)(mean age 65.5 years) were referred for internal medicine preoperative evaluation before elective surgery. Outpatient internist preoperative evaluation was performed 2 to 3 weeks before admission for surgery in the experimental arm with preoperative laboratory and radiology testing performed during the visit. The control arm was admitted for surgery without outpatient evaluation. The main outcome measure was the length of stay. Preoperative length of stay was significantly reduced from 2.9 days in the inpatient arm to 1.6 days in the outpatient arm (P < 0.001, 95% confidence interval of the difference, -0.8 to -1.8 days). Postoperative length of stay in the outpatient arm (3.6 days) was slightly but not significantly longer than the inpatient arm (3.0 days) (95% confidence interval of the increase, -0.6 to 1.8 days). Total length of stay showed no significant difference between the outpatient (5.5 days) and inpatient (6.0 days) arms (95% confidence interval of the difference, -2.0 to 1.1 days). Unnecessary admissions, defined as patients admitted who were admitted but did not undergo surgery, were decreased significantly comparing the inpatient arm (12.3%) to the outpatient arm (5.7%) (95% confidence interval of the difference, 0.5% to 12.7%). Measures of resource use showed no difference between arms including laboratory tests (95% C.I. of the difference, -3.0 to 6.8 tests), imaging tests (95% C.I. of the difference, -0.5 to 0.8 tests) were administered. A significant increase in the use of consultants between the outpatient arm (1.3 consultations) and inpatient arm (0.9 consultations) was discovered (95% C.I. of the difference, 0.2 to 0.6). Patients health status after discharge and satisfaction with care were not different between the two arms of the investigation. A program of outpatient internal medicine preoperative evaluation significantly reduced preoperative length of stay with a lesser effect on total length of stay. Unnecessary admission of patients for elective surgery were reduced by this program.