Centralized Pan-European survey on the undertreatment of hypercholesterolaemia (CEPHEUS).

The CEntralized Pan-European survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS) was initiated to quantify the degree of under-treatment of hypercholesterolaemia in Europe. Its primary objective was to establish the proportion of treated patients reaching the LDL-C goals according to the Third Joint European Task Force guidelines. Secondary objectives targeted subgroups of primary or secondary prevention patients and those with a metabolic syndrome. Further-more, CEPHEUS also aimed at the identification of determinants for under-treatment. Among the patients available for evaluation in Belgium (n=6276), 58.5% reached LDL-C goals as recommended by the 2003 European guidelines, 59.8% in primary prevention, 55.8% in secondary prevention, and 55.8% of those with a metabolic syndrome. The majority of patients (82.5%) was treated with statins. The univariate significant (P < 0.10) predictors of attaining LDL-C goal were the following: (a) nonsmoker, (b) no history of PAD or CAD, (c) absence of metabolic syndrome, (d) lower CV risk category, (e) absence of patient's concerns about treatment changes, (f) no withdrawal of lipid-lowering therapy when on target, (g) optimal. treatment adherence, (h) no patient's frustrations, (i) lipid-monitoring frequency, (j) physician being a specialist and (k) physicians finding it stressful to get patients on target. In an adjusted multi-level model, achievement of the LDL-C goals was significantly associated with: (a) type of lipid-lowering therapy, (b) risk category the patient fell into, (c) LDL-C level before initiating treatment, (d) patient's feelings about the treatment, (e) patient's acknowledgement about current cholesterol level and (f) self-reported drug compliance.

Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA study.

OBJECTIVE: The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode. METHODS: In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400-800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21. RESULTS: Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study. CONCLUSION: Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode.

Discovery Belux: comparison of rosuvastatin with atorvastatin in hypercholesterolaemia.

METHODS: Discovery Belux is an open-label, multicentre, randomised, phase IIIb, parallel group study comparing the efficacy of rosuvastatin (RSV) and atorvastatin (ATV) on changes in lipid levels and the achievement of European Atherosclerosis Society (EAS) lipid goals. Patients (> or = 18 years) with primary hypercholesterolaemia, with a low-density lipoprotein (LDL-C) level > 120 mg/dl (on treatment) or > 135 mg/dl (naive subjects), and with a statin indication, were randomised to receive RSV 10 mg/day or ATV 10 mg/day for 12 weeks. Patients not at goal after 12 weeks and receiving ATV 10 were further switched to RSV 10 mg for another 12 weeks. Patients not at goal with RSV 10 mg were further titrated to RSV 20 mg. RESULTS: 938 patients were randomised to the two treatment groups. After 12 weeks of treatment, a significantly greater percentage of patients receiving RSV 10 compared with ATV 10 achieved EAS LDL-C target goal (< 115 mg/dl) (85% vs. 67%). LDL-C was reduced by 47% and total cholesterol (TC) by 33% with RSV 10.This was 38% and 27% for ATV 10, respectively. After 24 weeks, an additional 57% of patients initially taking RSV 10 and uncontrolled, reached the target with RSV 20. In the patient group, initially taking ATV 10 and uncontrolled, 65% reached the target with RSV 10 after 24 weeks. Both treatments were well tolerated with a similar incidence of adverse events. In addition, a health economic analysis was performed. As RSV 10 is available at a lower cost in Belgium and as it is more effective, compared to ATV 10, it appeared to be the option of choice from a cost-effectiveness perspective. CONCLUSIONS: Rosuvastatin 10 mg treatment is significantly more effective than atorvastatin 10 mg at achieving European LDL-C goals, at lowering LDL-C and TC. These results were obtained with a similar safety profile. From a cost-effectiveness perspective RSV 10 is the preferred therapeutic option in comparison with ATV 10. Uptitration of uncontrolled patients to RSV 20 mg and switch from ATV 10 to RSV 10 allowed significantly more patients to reach the LDL-C and TC target goal.

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study.

Fulvestrant (Faslodex) is a new estrogen receptor (ER) antagonist with no agonist effects that is licensed for the treatment of postmenopausal women with hormone-sensitive advanced breast cancer (ABC) who have progressed/recurred on prior antiestrogen therapy. The Faslodex Compassionate Use Program (CUP) provides expanded access to fulvestrant in countries where it is not yet available for patients who are not eligible to enter clinical trials. This analysis pools data from 402 patients who received fulvestrant as part of the CUP in Belgium, predominantly as 3rd- to 5th-line endocrine therapy for ABC. Two patients experienced partial responses and 118 experienced stable disease lasting>or=6 months, resulting in an overall clinical benefit rate of 29.9%. Fulvestrant was active in patients with multiple sites of metastases, visceral metastases, human epidermal growth factor receptor 2-positive disease and after heavy endocrine pre-treatment. Fulvestrant was well tolerated, with only six patients (1.5%) discontinuing treatment following adverse events. These data support the findings of previous CUP analyses and Phase II and III trials, suggesting that fulvestrant is a valuable addition to the treatment sequence for postmenopausal women with ABC who have progressed/recurred on prior endocrine therapy.

Antihypertensive treatment based on home or office blood pressure--the THOP trial.

OBJECTIVE AND METHODS: In this randomized clinical trial, conducted in 400 hypertensive patients [sitting diastolic blood pressure (DBP) >95 mmHg], blood pressure-lowering therapy was adjusted in a stepwise manner, either on the basis of the self-measured DBP at home or on the basis of conventional DBP measured at the doctor's office. RESULTS: Therapy guided by home blood pressure instead of office blood pressure led to less intensive drug treatment and marginally lower costs, but also to less blood pressure control with no differences in left ventricular mass. Self-measurement helped to identify patients with white-coat hypertension. CONCLUSIONS: The present findings support a stepwise strategy for the evaluation of blood pressure, in which self-measurement and ambulatory monitoring are complementary to conventional office blood pressure measurement.

Budesonide-dependent modulation of expression of macrophage migration inhibitory factor in a polyposis model: evidence for differential regulation in surface and glandular epithelia.

Macrophage migration inhibitory factor (MIF) is a counterregulatory lymphokine for glucocorticoid action within the immune system. To provide further insights into the way expression of pleiotropically acting MIF is modulated by glucocorticoids, we investigated the influence of the glucocorticoid budesonide on the level of expression of MIF in a model of human nasal polyposis by quantitative immunohistochemical analysis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of 3 budesonide concentrations: 10, 50, and 250 ng/mL. As quantitatively demonstrated by computer-assisted microscopy, 50 ng/mL induced an increase in MIF expression in the surface epithelium and a decrease in MIF expression in the glandular epithelium. At the 250 ng/mL dose, the inverse effect was induced. Evidently, surface and glandular epithelia react nonuniformly to the glucocorticoid regarding MIF presence, adding dependence on the cell type to the regulatory network.

Antihypertensive treatment based on blood pressure measurement at home or in the physician's office: a randomized controlled trial.

CONTEXT: Self-measurement of blood pressure is increasingly used in clinical practice, but how it affects the treatment of hypertension requires further study. OBJECTIVE: To compare use of blood pressure (BP) measurements taken in physicians' offices and at home in the treatment of patients with hypertension. DESIGN, SETTING, AND PARTICIPANTS: Blinded randomized controlled trial conducted from March 1997 to April 2002 at 56 primary care practices and 3 hospital-based outpatient clinics in Belgium and 1 specialized hypertension clinic in Dublin, Ireland. Four hundred participants with a diastolic BP (DBP) of 95 mm Hg or more as measured at physicians' offices were enrolled and followed up for 1 year. INTERVENTIONS: Antihypertensive drug treatment was adjusted in a stepwise fashion based on either the self-measured DBP at home (average of 6 measurements per day during 1 week; n = 203) or the average of 3 sitting DBP readings at the physician's office (n = 197). If the DBP guiding treatment was above (>89 mm Hg), at (80-89 mm Hg), or below (<80 mm Hg) target, a physician blinded to randomization intensified antihypertensive treatment, left it unchanged, or reduced it, respectively. MEAN OUTCOME MEASURES: Office and home BP levels, 24-hour ambulatory BP, intensity of drug treatment, electrocardiographic and echocardiographic left ventricular mass, symptoms reported by questionnaire, and costs of treatment. RESULTS: At the end of the study (median follow-up, 350 days; interquartile range, 326-409 days), more home BP than office BP patients had stopped antihypertensive drug treatment (25.6% vs 11.3%; P<.001) with no significant difference in the proportions of patients progressing to multiple-drug treatment (38.7% vs 45.1%; P =.14). The final office, home, and 24-hour ambulatory BP measurements were higher (P<.001) in the home BP group than in the office BP group. The mean baseline-adjusted systolic/diastolic differences between the home and office BP groups averaged 6.8/3.5 mm Hg, 4.9/2.9 mm Hg, and 4.9/2.9 mm Hg, respectively. Left ventricular mass and reported symptoms were similar in the 2 groups. Costs per 100 patients followed up for 1 month were only slightly lower in the home BP group (3875 vs 3522 [4921 dollars vs 4473 dollars]; P =.04). CONCLUSIONS: Adjustment of antihypertensive treatment based on home BP instead of office BP led to less intensive drug treatment and marginally lower costs but also to less BP control, with no differences in general well-being or left ventricular mass. Self-measurement allowed identification of patients with white-coat hypertension. Our findings support a stepwise strategy for the evaluation of BP in which self-measurement and ambulatory monitoring are complementary to conventional office measurement and highlight the need for prospective outcome studies to establish the normal range of home-measured BP.

Patients' experience of pain and discomfort during instrumentation in the diagnosis and non-surgical treatment of periodontitis.

BACKGROUND: The present multicenter study aimed to survey the patients' experiences in relation to the diagnosis and non-surgical treatment of periodontitis according to current treatment routine. METHODS: Patients (N = 268) treated for plaque-related periodontitis were enrolled in two groups: group 1 received primary probing of pocket depths (PD 1) and/or primary scaling and root planing (SRP 1); group 2 consisted of patients who were scheduled in the different centers for recall PD/scaling/subgingival instrumentation. Data collection included a full periodontal status, anesthesia employed, procedure time, and patient self-completed questionnaires to assess their previous and current experience of pain and discomfort during anesthesia and periodontal treatment. RESULTS: Ninety percent of the patients received infiltration anesthesia during primary SRP, compared to only 2% during recall scaling/instrumentation and none during PD. Many patients (40% in SRP group 1 and 52% in the recall scaling/instrumentation group) were most bothered by the scaling procedure, while others (35% in the primary SRP patients) by the anesthetic injection. Painful experiences during previous primary PD and present SRP were highly correlated (r = 0.6). CONCLUSIONS: From these results, it is evident that subgingival instrumentation causes pain and discomfort, an aspect that should be considered in periodontal therapy. Unfortunately, the use of local infiltration anesthesia to reduce pain is in itself a cause of discomfort. Attractive alternatives for anesthetic applications are much needed.

Self-measured versus ambulatory blood pressure in the diagnosis of hypertension.

OBJECTIVE: We examined to what extent self-measurement of blood pressure at home (HBP) can be an alternative to ambulatory monitoring (ABP) to diagnose white-coat hypertension. METHODS: In 247 untreated patients, we compared the white-coat effects obtained by HBP and ABP. The thresholds to diagnose hypertension were > or = 140/> or = 90 mmHg for conventional blood pressure (CBP) and > or = 135/> or = 85 mmHg for daytime ABP and HBP. RESULTS: Mean systolic/diastolic CBP, HBP and ABP were 155.4/100.0, 143.1/91.5 and 148.1/95.0 mmHg, respectively. The white-coat effect was 5.0/3.5 mmHg larger on HBP compared with ABP (12.3/8.6 versus 7.2/5.0 mmHg; P < 0.001). The correlation coefficients between the white-coat effects based on HBP and ABP were 0.74 systolic and 0.60 diastolic (P < 0.001). With ABP as a reference, the specificity of HBP to detect white-coat hypertension was 88.6%, and the sensitivity was 68.4%. CONCLUSION: Our findings are in line with the recommendations of the ASH Ad Hoc Panel that recommends HBP for screening while ABP has a better prognostic accuracy.

Determinants of white-coat syndrome assessed by ambulatory blood pressure or self-measured home blood pressure.

BACKGROUND: Gender, age, smoking, race, and body mass index have been reported to determine the ambulatory white-coat effect (WCE) and white-coat hypertension (WCH). METHODS: Baseline conventional, day-time ambulatory and self-measured home blood pressure measurements from the THOP trial were used to study the effect of gender, age, body mass index, smoking habits and treatment status on the white-coat syndrome as assessed by ambulatory monitoring or self-measurement. RESULTS: The mean systolic/diastolic WCE was 9.1/6.7 mmHg if based on ambulatory blood pressure and 12.2/8.7 mmHg if based on self-measured blood pressure. The ambulatory WCE was significantly higher in women, in older subjects (65+), in obese subjects, in non-smokers and in patients on antihypertensive drug treatment. The self-measured WCE was significantly higher in women and in non-smokers. Ambulatory WCH was present in 6.6% of the untreated patients and 14.2% had self-measured WCH. The proportion of ambulatory WCH was significantly higher in obese subjects; the proportion of self-measured WCH did not differ by gender, age, body mass index, or smoking habits. CONCLUSIONS: The ambulatory white-coat syndrome was determined by gender, age, body mass index, smoking habits, and treatment status. The self-measured white-coat syndrome was greater than the ambulatory white-coat syndrome but depended less on the determinants under study.

Glucocorticoid-induced differential expression of the sialylated and nonsialylated Lewis(a) epitopes and respective binding sites in human nasal polyps maintained under ex vivo tissue culture conditions.

We characterized the anti-inflammatory effects of budesonide on the expression of adhesion molecules involving Lewis(a) (Le(a)) epitope, its sialylated derivative (sLe(a)), and their respective binding sites in human nasal polyposis. By computer-assisted microscopy, we quantitatively characterized the level of histochemical expression of L- and P-selectins, sialylated and nonsialylated Le(a) epitopes, and their respective binding sites in both surface epithelium and glandular epithelium of human nasal polyps obtained from surgical resection, maintained under ex vivo tissue culture conditions for 24 hours, and treated or not with budesonide. Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were chosen as methodological controls, because data already published in the literature clearly indicated budesonide-mediated effects on ICAM-1 and VCAM-1 levels of expression. The present data show that budesonide significantly modified the levels of expression of ICAM-1 and VCAM-1, and to a lesser extent that of P-selectin, in the surface and glandular epithelia. Budesonide markedly decreased the levels of expression of the binding sites for both Le(a) and sLe(a), while those of Le(a) and sLe(a) remained globally unchanged. In conclusion, the present study documents that glucocorticoid-induced effects can encompass receptors for Le(a) epitopes different from E- and P-selectins on epithelial cells of human nasal polyps.

Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration.

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.