[Treatment decision as a function of cardiovascular risk in isolated systolic hypertension in general medicine. The PREHSI study]. / Décision thérapeutique en fonction du risque cardiovasculaire dans l'HTA systolique isolée en médecine générale. Etude PREHSI.

OBJECTIVE: To analyse the decision of treatment made by the GP, based on the characteristics of patients with isolated systolic hypertension (ISH). METHODS: 11,436 patients with SBP > or = 140 and DBP < 90 mmHg were examined by 1,464 GPs who filled out a questionnaire for each patient, which included the patient's BP, risk factors, the presence of target organ damage (TOD), antihypertensive treatment and the physician's decision of treatment during the visit. Before the visit, 4,378 patients were not treated: 57 +/- 13 years: 53% men: BP: 157/81 mmHg; smokers: 30%; diabetes: 8%; dyslipidemia: 17%; BMI > 25 kg/m2: 54%; TOD: 11%. Thus, according to ISH tables, 15% of the patients who were not treated presented a low cardiovascular risk (LR), 69% a medium risk (MR), and 16% a high risk (HR). After the visit, 2,599 patients (59%) started antihypertensive treatment. [table: see text] CONCLUSION: 78% of the patients with ISH had at least one other risk factor. Three elements (the grade of ISH, the number of risk factors and the level of CV risks) are significantly taken into account in making the decision of treatment. Decision of treatment was in accordance with ISH recommendation in 91% of patients. Nevertheless, while ISH recommendations are life style measures, only when a LR exists, 39% with a LR were treated. On the other hand, 24% with a HR were not treated.

[Characteristics of patients with isolated systolic hypertension in relation to body mass index. The PREHSI study]. / Caractéristiques des patients avec une HTA systolique isolée en fonction de la masse corporelle. Etude PREHSI.

OBJECTIVE: To analyse patient's isolated systolic hypertension (ISH) in relation to the body mass index (BMI). METHODS: 11,436 patients with SBP > or = 140 and DBP < 90 mmHg were examined by 1,464 GPs who filled in a questionnaire for each patient: the patient's BP, risk factors, the presence of target organ damage (TOD) and antihypertensive treatment. 11,100 patients were split into 3 groups depending on their BMI: Gp 1 (BMI < 25 kg/m2: 4,324), 39%; 62 +/- 14 yrs; 44% men; BP: 157/80 mmHg, 55% treated; Gp 2 (BMI 25 and 30 kg/m2: 5,164) 47%; 62 +/- 12 yrs; 61% men; BP: 158/81 mmHg, 63% treated; and Gp 3 (BMI > 30 kg/m2: 1,612) 14%; 62 +/- 12 yrs; 49% men; BP: 159/81 mmHg, 75% treated. 11,085 patients' CV risks were analysed and categorised into high (HR), medium (MR) and low risk (LR). [table: see text] 11,100 patients' CV history (CVH) were analysed: > 1 CVH were 1,056 (24%) into Gp 1; 1,531 (30%) into Gp 2 and 653 (41%) into Gp 3; left ventricular hypertrophy was 454 (10%) into Gp1; 815 (16%) into Gp 2 and 388 (24%) into Gp 3. CONCLUSION: 61% patients with ISH carry excess weight and 14% are obese. In spite of a more frequent antihypertensive treatment which gives comparable BP levels, the higher the BMI, the higher the CV risk and CV history. Treatment of all CV risks is therefore necessary.

Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients.

The aim of this study was to investigate the cognitive and electroencephalography (EEG) short-term effects of a calcium antagonist, nicardipine, compared to placebo and clonidine (which, having known sedative effects, acted as a negative control) for 15 days in elderly hypertensive patients with memory complaints. Nicardipine and clonidine were compared with placebo in a double-blind, randomized, three-way cross-over controlled study after a 2-week placebo run-in period. This was a phase II clinical study carried out on out-patients in a single research centre. Fifteen elderly (63 +/- 10 years) hypertensive patients, without dementia but with memory complaints, were included. Psychomotor performance and cognition were assessed using both an extensive battery of validated psychometric tests (which evaluated attention and vigilance, body sway and memory) and an EEG profile. Cardiovascular parameters measured were blood pressure and heart rate. No detrimental effects of nicardipine were found on attention, vigilance, body sway or memory. Nicardipine produced a significant increase in alpha EEG energies, which may indicate possible alerting effects. In contrast, clonidine induced well-known deleterious sedative effects in psychometric tests and in EEG analysis (decrease in alpha and increase in delta and theta waves). The two drugs produced equivalent decreases in blood pressure at steady state. In conclusion, clonidine induced well-known sedative effects, while nicardipine did not impair central nervous system activity and may have had some short-term alerting effects in elderly hypertensive patients with memory complaints. This study supports the hypothesis of a dissociation between blood pressure and direct drug effects on the central nervous system.

Cognitive performance in elderly subjects after a single dose of befloxatone, a new reversible selective monoamine oxidase A inhibitor.

BACKGROUND: Patients with depression often have cognitive and psychomotor performance impairments. Antidepressive treatments can correct these deficits, provided sedative and anticholinergic adverse effects do not add to the preexisting condition, particularly in elderly patients. Newly developed antidepressants therefore should be without deleterious effects on cognitive functions, including memory. Befloxatone is a new antidepressant with a potent, selective, competitive, and reversible inhibitory activity on the A isoform of monoamine oxidase (MAO-A). METHODS: The effects on cognition and psychomotor performance of single oral doses of befloxatone (10 mg) and amitriptyline (50 mg) were compared in a randomized, double-blind, placebo-controlled, three-way crossover design trial in 12 healthy elderly (65 to 85 years) volunteers. The performances of the subjects were evaluated by a comprehensive battery of validated psychometric tests that explored alertness, psychomotor performance, information processing, and memory. Subjective feelings on mood and sleep were rated on visual analog scales. MAO-A inhibition was estimated by multiple titrations of 3,4-dihydrophenylglycol (DHPG) in plasma. RESULTS: Amitriptyline displayed the expected deleterious effects on performance tasks, critical flicker fusion threshold, digit symbol substitution, and body sway, and it deteriorated memory (immediate and delayed free recall of words). In contrast, befloxatone did not impair cognition or psychomotor performance but instead significantly improved the delayed free recall. Amitriptyline adversely affected subjective feelings of alertness and contentedness, but befloxatone permitted sustained alertness and did not alter other subjective feelings or sleep. Concurrently, a single dose of 10 mg befloxatone markedly decreased the DHPG concentration in plasma. CONCLUSION: Contrary to tricyclic antidepressants, whose deleterious effects are greater in elderly subjects, this study demonstrated the safety of befloxatone on cognition and psychomotor performance in elderly subjects.

Lack of effect of mizolastine on the safety and pharmacokinetics of digoxin administered orally in repeated doses to healthy volunteers.

The effects of mizolatine, a new H1 receptor antagonist, on safety and pharmacokinetics of digoxin were studied in a double-blind placebo-controlled crossover study. After administration of digoxine alone (0.25 mg o.d. for 7 days), 12 healthy young male volunteers (23+/-2 years) received either placebo and digoxin (0.25 mg o.d.) or mizolastine (10 mg o.d.) and digoxin (0.25 mg o.d.) during 7 days. The assessment criteria consisted in hemodynamic and ECG parameters recordings and the pharmacokinetics of digoxin during the last day of coadministration (day 14). No difference between the 2 treatment groups was evidenced on ECG, hemodynamic, and clinical and laboratory safety parameters. No change in AUC and tmax was recorded. No clinically relevant effect of mizolastine on the digoxin pharmacokinetics was found. However, a statistically significant increase in digoxin Cmax (3.03+/-0.18 nmolxl(-1) vs 2.52+/-0.19 nmolxl(-1), p < 0.05) and Cmin (0.99+/-0.08 nmolxl(-1) vs 0.87+/-0.07 nmolxl(-1), p=0.05) occurred after the coadministration vs digoxin alone. It can be concluded that mizolastine and digoxin at therapeutic dosages can be safely coadministered.

[Baseline blood pressure in healthy normotensive volunteers]. / Etat basal de la pression artérielle chez le volontaire sain normotendu.

UNLABELLED: The aim of this study was to define the reproducibility and the time required to obtain a stable baseline level of blood pressure (BP) in normotensive volunteers during a phase I trial. Blood pressure was recorded automatically (Dinamap and Marquette monitors) every 5 min during a 2-hour period and manually (Random zero device) at T20, T60 and T120, twice at a one-week interval, under similar study conditions (6 in the morning, 7 in the afternoon) in supine position in 13 normotensive men (aged 20 to 28). The average BP was compared using a 3-way ANOVA (subject, time, week). 1.SBP/DBP decreased significantly (p < 0.001) from one week to the other and SBP, but not DBP, decreased significantly over time up to T75 (p < 0.001): [table: see text] 2. SBP was significantly higher in the morning than in the afternoon during both weeks (p = 0.001). The decrease in SBP with rest was only observed in the morning (p = 0.00001). 3. Reproducibility and change over time and period did not significantly differ between manual and oscillometric methods. The best reproducibility of T75 was obtained with the mean of 3 automatic values (T70, T75, T80). CONCLUSION: in normotensive subjects, BP decreased from one period to the next and with rest. The baseline value of BP was obtained from T75 with the best reproducibility when baseline BP level is defined by 3 automatic values.

Predicting factors for absenteeism in patients with major depressive disorders.

This study examines the predicting factors for absenteeism in depressed patients. Using a 'cross-sectional' design, we observed 345 patients diagnosed with major depressive disorders as assessed by the Diagnostic and Statistical Manual for Mental Disorders, third edition revised (DSM-III-R) criteria and Hamilton Depression Rating Scale (HAM-D) [12] score higher than 12. The treatment group (n = 268) were treated with antidepressants (n = 98 with fluoxetine and n = 170 with tricyclics [amitriptyline, clomipramine]) for at least one week and the non treated group (n = 67) had not received antidepressants for at least one month. Sociodemographic, clinical and therapeutic data was collected. The primary endpoint was absenteeism from work. Logistic regression analysis of these data was used to identify potential predictive variables. The rate of absenteeism from work was greater in non treated (70.2%) compared to treated patients (39.8% for fluoxetine group and 57.7% for tricyclics group). The risk of absenteeism for patients treated with tricyclics was 2.45 times greater than for patients treated with fluoxetine (odds-ratio = 2.45, CI 95% = 1.1-4.7). For all patients, the strongest predictors of absenteeism from work were symptom severity (odds-ratio = 44.4, CI 95% = 7.9-250) followed by past history of depression (odds-ratio = 6.85, CI 95% = 2.6-18.4) and past history of absenteeism (odds-ratio = 6.51, CI 95% = 2.0-204). In conclusion, the risk of absenteeism from work increases with depression severity and is higher with tricyclics compared to fluoxetine.

Pharmacodynamics and pharmacokinetics of two dose regimens of befloxatone, a new reversible and selective monoamine oxidase inhibitor, at steady state in healthy volunteers.

The pharmacodynamic equipotency of 2 dose regimens (5 mg twice daily versus 10 mg once daily) of befloxatone, a new reversible and selective monoamine oxidase A (MAO-A) inhibitor, after single and multiple doses for 6 days was examined in a randomized, double-blind, three-way crossover, placebo-controlled trial of 12 healthy volunteers. Plasma levels of the deaminated metabolite 3-4 dihydroxyphenylglycol (DHPG), as measured by high-performance liquid chromatography (HPLC) with coulometric electrochemical detection, were used as an index of MAO inhibition. A single dose of befloxatone produced a significant dose-related reduction in plasma DHPG levels, as shown by the decrease in the 24-hour area under the concentration-time curve (AUC0-24) of DHPG, which peaked 2 hours after administration and persisted over 24 hours. Both dose regimens provided equipotent extent and duration of MAO-A inhibition at steady state, suggesting a once daily dosage should be sufficient for most patients. The pharmacokinetic bioavailability at steady state of both dose regimens was also similar. The concentration-time effect curve after a single dose revealed a hysteresis corresponding to the delay necessary to elicit MAO inhibition and/or elimination of DHPG. The relationship between plasma levels of DHPG and/or elimination of plasma concentrations of DHPG and befloxatone after a single dose can be modeled using the Emax model with a mean EC50 of 4.75 ng/mL, and suggests the presence of a maximal response from the single dose. This model permits prediction of steady-state levels of DHPG.

Cost of anxiety disorders: impact of comorbidity.

The aim of this study was to assess the relative impact of co-mobidity and of symptom severity on the costs of caring for patients with generalized anxiety disorders (GAD). One thousand and forty-two patients with GAD according to DSM III-R were observed by psychiatrists using a cross-sectional methodology. Demographic, clinical, therapeutic as well as health care utilization data were collected at a single point in time. Patients were stratified according to prevalence of co-morbidity. An economic analysis was performed based on a societal perspective. Hospitalizations and losses of productivity were the two major components of costs both in patients with and without co-morbidity. On the other hand costs of pharmaceuticals remain a marginal component of costs associated with GAD in the two groups. Controlling for confounding variables, the prevalence of health care utilisation was found to be significantly higher in patients with co-morbidity for hospitalization, laboratory tests, medications and absenteeism from work. Most of cost components were found to be significantly higher in patients with co-morbidity. The relative risk of health care utilization was higher in patients with co-morbidity, past history of anxiety, high level of anxiety as well as in older patients. Overall our findings suggest that both co-morbidity and symptom severity play a role in cost generation in GAD patients.

Risk factors for infertility in nursing cows linked to calving.

An ecopathological survey was conducted between 1987 and 1989 in 116 French herds with 3,590 cows in order to study the risk factors for infertility linked to calving. Based upon an analysis model of etiological interactions, the complementary use of a logistic model and factorial analysis followed by classification allowed demonstration of the direct and indirect, effects upon infertility, breed factors, parity, fattening, comfort, calf characteristics (number, sex, weight, presentation), as well as the difficulty and complications which may have been associated with calving. By association, these factors determine the profile of the cows at risk.

Risk factors of dairy cow lameness associated with housing conditions.

In 1987, an ecopathology survey was carried out in 160 French dairy farms in order to specify lesions typical of laminitis and heelhorn erosion and to assess their risk factors. Three podal affections were characterized: chronic laminitis; subacute laminitis; and heelhorn erosion. Concerning the building for livestock, the risk factors of heelhorn erosion were associated with poor hygiene, while the risk factors of subacute laminitis were linked to uncomfortable housing conditions: high steps and slopes, and discomfort when lying down and getting up. No risk factor of chronic laminitis linked to the building for livestock was identified.