Publications

PURPOSE

Because limited audit/feedback of health status information has yielded mixed results, we evaluated the effects of a sustained program of audit/feedback on patient health and satisfaction.

METHODS

We conducted a group-randomized effectiveness trial in which firms within Veterans Administration general internal medicine clinics served as units of randomization, intervention, and analysis. Respondents to a baseline health inventory were regularly mailed the 36-Item Short Form (SF-36) and, as relevant, questionnaires about six chronic conditions (ischemic heart disease, diabetes, chronic obstructive pulmonary disease, depression, alcohol use, and hypertension) and satisfaction with care. Data were reported to primary providers at individual patient visits and in aggregate during a 2-year period.

RESULTS

Baseline forms were mailed to 34,050 patients; of the 22,413 respondents, 15,346 completed and returned follow-up surveys. Over the 2-year study, the difference between intervention and control groups (as measured by difference in average slope) was -0.26 (95% confidence interval [CI]: -0.79 to 0.27; P=0.28) for the SF-36 Physical Component Summary score and -0.53 (95% CI: -1.09 to 0.03; P=0.06) for the SF-36 Mental Component Summary score. No significant differences emerged after adjusting for deaths. There were no significant differences in condition-specific measures or satisfaction between groups after adjustment for provider type, panel size, and number of intervention visits, or after analysis of patients who completed all forms.

CONCLUSION

An elaborate, sustained audit/feedback program of general and condition-specific measures of health/satisfaction did not improve outcomes. To be effective, such data probably should be incorporated into a comprehensive chronic disease management program.

Atrial conduction properties have been shown to differ among animal atrial fibrillation (AF) models of rapid atrial pacing (RAP), chronic mitral regurgitation (MR), and control. We hypothesized that these conduction differences would continue with the onset of AF, which would affect AF spatiotemporal organization, resulting in model-specific characteristics of AF. With frequency domain analysis of electrograms acquired from high-density optical mapping, AF from the right (RA) and left (LA) atrium in animals with RAP and MR were compared with control animals. At follow-up, the hearts were excised and perfused, and optical action potentials were recorded from a 2 x 2-cm area each of the RA and LA free wall with a 16 x 16 photodiode array. AF was induced with extra stimuli, several 2.4-s AF episodes were recorded in each dog, and a fast Fourier transform was calculated. The dominant frequency (DF) was determined, and the organization (organization index, OI) was calculated as the ratio of the area under the dominant peak and its harmonics to the total area of the spectrum. All possible pairs of electrograms for each episode were cross-correlated. LA AF in the chronic MR model showed an increase in the highest DF, the number of DF domains, and in frequency gradient compared with AF in control or RAP models. In addition, there was a decrease in OI and in the correlation coefficients in the LA of the MR model. These results suggest that the AF substrate in the MR model may be different from that of control or RAP models.

Activation of the NF-kappaB/Rel family of transcription factors proceeds through a catalytic complex containing IkappaB kinase (IKK)-1 and IKK2. Targeted disruption of each of the IKK genes suggests that these two kinases may mediate distinct functions in the activation pathway. In our studies of the human T-cell lymphotropic virus type 1 (HTLV-1) Tax oncoprotein, we have uncovered a new function of IKK1 required for complete activation of the NF-kappaB transcriptional program. In IKK1(-/-) murine embryonic fibroblasts (MEFs), Tax normally induced early NF-kappaB activation events. However, NF-kappaB induced by Tax in these IKK1(-/-) cells was functionally impaired. In IKK1(-/-) (but not wild-type) MEFs, Tax failed to activate several different kappaB reporter constructs or to induce the endogenous IkappaBalpha gene. In contrast, Tax normally activated the cAMP-responsive element-binding protein/activating transcription factor pathway, leading to full stimulation of an HTLV-1 long terminal repeat reporter construct in IKK1(-/-) cells. Furthermore, reconstitution of IKK1(-/-) cells with kinase-proficient (but not kinase-deficient) forms of IKK1 restored the Tax induction of full NF-kappaB transactivation. We further found that the defect in NF-kappaB action in IKK1(-/-) cells correlated with a failure of Tax to induce phosphorylation of the RelA/p65 subunit of NF-kappaB at Ser(529) and Ser(536). Such phosphorylation of RelA/p65 was readily detected in wild-type MEFs. Phosphorylation of Ser(536) was required for a complete response to Tax expression, whereas phosphorylation of Ser(529) appeared to be less critical. Together, these findings highlight distinct roles for the IKK1 and IKK2 kinases in the activation of NF-kappaB in response to HTLV-1 Tax. IKK2 plays a dominant role in signaling for IkappaBalpha degradation, whereas IKK1 appears to play an important role in enhancing the transcriptional activity of NF-kappaB by promoting RelA/p65 phosphorylation.