Anxiety and outcome expectations predict the white-coat effect

OBJECTIVE: To determine whether elevated clinic blood pressure compared with daytime ambulatory blood pressure, referred to as the white-coat effect, is associated with anxiety and increased blood pressure expectancy in the doctor's office. METHODS: The 24-h ambulatory blood pressure measurements and physicians' blood pressure measurements were obtained in 226 normotensive and hypertensive study participants. Anxiety levels were assessed multiple times during the clinic visit using a Visual Analog Scale. Participants' expectations regarding the clinic visit were assessed using a six-item scale (Expectations of Outcomes Scale). The white-coat effect was computed as the difference between the mean clinic blood pressure and the mean daytime ambulatory blood pressure. Multiple regression analysis was performed to examine the association between anxiety, outcome expectations and the white-coat effect, adjusting for age, sex, and ambulatory blood pressure level. RESULTS: As predicted, outcome expectations and anxiety during the clinic visit were significantly associated with the white-coat effect. Results of the regression analysis indicated that only expectancy had an independent effect on the systolic white-coat effect; however, both anxiety and expectancy had independent effects on the diastolic white-coat effect. CONCLUSION: Our results provide empirical support to the hypothesis that anxiety and blood pressure expectancy may elevate clinic blood pressure.     

Titration of the infectivity of hepatitis D virus in chimpanzees

The infectivity of hepatitis D virus (HDV) was evaluated by intravenous inoculation of chimpanzees. HDV was present in the inoculum at a titer of 10(11) chimpanzee infectious doses (CID). In contrast, the titer of hepatitis B virus (HBV) in the same inoculum was 10(6) CID. All HBV-infected chimpanzees inoculated with less than or equal to 10(-11) dilutions of the HDV-positive plasma were superinfected; an animal receiving a 10(-12) dilution did not develop markers of HDV replication in serum or liver. All HDV-infected chimpanzees had marked elevations of serum alanine aminotransferase activities. The incubation period from exposure to development of hepatitis was inversely related to the dose of HDV inoculum, although the severity and duration of hepatitis were independent of it. All animals recovered and rapidly developed antibody to hepatitis D antigen.     

Treatment of chronic woodchuck hepatitis virus infection in the Eastern woodchuck (Marmota monax) with nucleoside analogues is predictive of therapy for chronic hepatitis B virus infection in humans

The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a model of hepatitis B virus (HBV)-induced disease. Several published studies have used this experimental animal model system to demonstrate potential antiviral therapies for chronic HBV infections. However, there has been little comparative information available on compounds used in clinical anti-HBV studies in WHV-infected woodchucks, thereby making interpretations of the potential relative effectiveness of new antiviral agents in humans more difficult. In this report, using a series of placebo-controlled studies, we compared the relative effectiveness of several nucleoside analogues that have been used in clinical trials for the treatment of chronic HBV infection against WHV replication in chronically infected woodchucks. Adenine-5'-arabinoside monophosphate (Ara-AMP [vidarabine]), ribavirin, (-)beta-L-2',3'-dideoxy-3'-thiacytidine (3TC [lamivudine]), and famciclovir (oral prodrug of penciclovir) induced depressions in viremia and intrahepatic WHV-DNA replication that were consistent with their relative effectiveness in anti-HBV human clinical trials. As observed in HBV-infected patients, 3' azido-3'-deoxythymidine (AZT [zidovudine]) had no effect on WHV replication in these studies. These experimental results more firmly establish chronic WHV infection in woodchucks as an accurate and predictive model for antiviral therapies against chronic HBV infection in humans and provide a baseline for comparative antiviral effects of other experimental antiviral agents in the WHV/woodchuck model system.     

Course of depressive symptoms and medication adherence after acute coronary syndromes: an electronic medication monitoring study.

OBJECTIVES: We tested whether improvements in depressive symptoms precede improved adherence to aspirin in patients with acute coronary syndromes (ACS). BACKGROUND: Depression is associated with medication nonadherence in patients with ACS, but it is unclear whether changes in depression impact on adherence. METHODS: Electronic medication monitoring was used to measure adherence to aspirin during a 3-month period in a consecutive cohort of 172 patients (25 to 85 years) recruited within 1 week of hospitalization for ACS. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI) during hospitalization and at 1 and 3 months after hospitalization. Adherence was defined as the percentage of days aspirin was taken as prescribed. RESULTS: Depression severity in hospital was associated with nonadherence in a gradient fashion: 15% of non-depressed patients (BDI score 0 to 4), 29% of mildly depressed patients (BDI score 10 to 16), and 37% of patients with moderately-to-severely depressive symptoms (BDI score >16) took aspirin less than 80% of the time (p = 0.03). A cross-lagged path analytic model revealed that improvements in depressive symptoms in the first month after the ACS were associated with improvements in adherence rates in the subsequent 2 months (standardized direct effect -0.32, p = 0.016). CONCLUSIONS: Diagnosis and treatment of depressive symptoms may improve medication adherence in patients after ACS.     

Integration of woodchuck hepatitis and N-myc rearrangement determine size and histologic grade of hepatic tumors

Integrations of woodchuck hepatitis virus (WHV) DNA and rearrangements of the N-myc 2 gene have been detected frequently in hepatocellular carcinoma (HCC) of Eastern woodchucks (Marmota monax) chronically infected with WHV. Fifty-five hepatocellular neoplasms and matched nontumor hepatic tissue specimens obtained postmortem from 13 chronic WHV carriers were analyzed and the frequency of WHV DNA integrations and of N-myc rearrangements compared in tumors of different size and histologic grade. Four small tumor nodules were classified histologically as adenomas and integrated sequences of WHV DNA were detected in two of the four tumor nodules. In one of the two nodules, there was evidence of N-myc rearrangement. Fifty-one neoplasms were classified as HCC. Seven were grade 1 HCCs. WHV DNA integrations were demonstrated in 43% but none had N-myc rearrangements. Twenty grade 2 HCCs had WHV DNA integrations in 80% and in 38% N-myc rearrangements were present. Twenty-four grade 3 HCCs had integrations of WHV DNA in 79% and N-myc rearrangements in 74%. In two other grade 3 HCCs, rearrangements of N-myc were detected in the absence of WHV DNA integrations. The 12 largest tumors in the series all were grade 2 or 3 HCCs, and in 83%, both WHV DNA integrations and N-myc rearrangements were demonstrated. In conclusion, molecular changes observed in this study suggest a progression of genetic alterations providing either a significant proliferative stimulation and/or a growth advantage in hepatocarcinogenesis of woodchucks with chronic WHV infection.     

The impact of perceived hypertension status on anxiety and the white coat effect

Background: The white coat effect can lead to overdiagnosis of hypertension and unnecessary pharmacologic treatment. Mechanisms underlying the white coat effect remain poorly understood but are critical to improving the accuracy of clinic blood pressure measurement.Purpose: This study investigated whether perceived hypertension status was associated with state anxiety levels during a clinic visit and the magnitude of the white coat effect, independent of true blood pressure status.Methods: This observational study included 214 normotensive and mildly hypertensive participants who were 18 to 80 years old, had no cardiac history, and were willing to discontinue antihypertensive medications for 8 weeks. Participants underwent 36 hr ambulatory blood pressure monitoring and physician blood pressure measurement. Outcome measures were state anxiety reported during the clinic visit and the white coat effect.Results: An analysis of covariance indicated that participants who perceived themselves as hypertensive reported greater state anxiety (p<.001) and showed larger white coat effects (ps<.01) compared with those who perceived themselves as normotensive. True hypertension status based on ambulatory blood pressure was not related to either outcome. Anxiety accounted for approximately 19% of the association between perceived hypertension status and the white coat effect.Conclusions: These findings suggest that the perception of being hypertensive is associated with greater anxiety during clinic blood pressure measurement and a larger white coat effect, independent of the true blood pressure level. Anxiety appears to be a mechanism by which perceived hypertension status contributes to the white coat effect. Preparation of this article was supported in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, Grants HL47540 and HL76857, T. G. Pickering, Principal Investigator. The sponsors had no role in the study design; in the collection, analysis, or interpretation of the data; in the writing of this article; or in the decision to submit the article for publication.