Essential competencies in prescribing: A first european cross-sectional study among 895 final-year medical students.

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.

[Medication reconciliation at hospital discharge focusing on patient with hypertension: Analysis of the output prescription]. / Conciliation médicamenteuse à la sortie d'hospitalisation du patient hypertendu : analyse de l'ordonnance de sortie.

PURPOSE: To describe pharmacists' interventions made at patients hospital discharge from Department of Hypertension. METHODS: This is a single-center and prospective study over an 8-week period. At hospital discharge, the pharmacist compared pre-admission and inpatient medications with discharge orders and written instructions. Pharmacists' interventions were then classified in 4 categories. All variances and discrepancies were discussed with the prescribing physician when possible. RESULTS: Over the 8-week period, 154 cases were analyzed. Pharmacists' interventions at discharge underwent 48 times on 21% of the patients (n=33) but none was clinically relevant. Among these 48 cases, 40% (n=19) were rated as "inappropriate administration", 27% (n=13) were classified as "incomplete prescription", 19% (n=9) were "variances" and 4% (n=2) were due to "omission prescription". In 10% of the cases (n=5), discrepancies appeared without any possible further analysis as no discussion with the prescriber occurred. CONCLUSION: One fifth of all patients analyzed was the subject of a pharmacists' intervention. The complementary action of the pharmacist improves the consistency of the prescriptions and strengthens patient safety.

Causes of secondary hypertension in the young population: A monocentric study.

OBJECTIVE: To study the prevalence of different causes of hypertension in young adults referred to a hypertension center in the south west of France. METHODS: We conducted a retrospective overview of patients younger than 40years old hospitalized consecutively in the Hypertension department of Toulouse University Hospital between 2012 and 2014. Clinical data about gender, age, anthropomorphic parameters and blood pressure measurement by 24h Ambulatory Blood Pressure Monitoring (ABPM) were recorded. Biological data concerned dosages of kalemia, renin and aldosterone in the supine or after 15min of seating. Recorded radiological examinations were renal artery ultrasound and abdominal CT scan. RESULTS: One hundred and forty-eight detailed medical records were analyzed, 69 women and 79 men. Among the 69 women, the causes of secondary hypertension were primary aldosteronism (n=7), fibromuscular dysplasia (n=5) and renal disease (n=4). Oral contraceptives were involved in 13 women. In addition, essential hypertension concerned 40 women (58%). Among the 79 men, the causes of secondary hypertension were primary aldosteronism (n=10), fibromuscular dysplasia (n=3), left main renal artery entrapment by a diaphragmatic crura (n=2), renal disease (n=1), pheochromocytoma (n=3) and coarctation of the aorta (n=2). In addition, essential hypertension concerned 58 men (73%). CONCLUSIONS: In our population, the prevalence of secondary hypertension is close to 33% (42% of females and 27% of males), with the following main causes: primary aldosteronism for 11.5%; fibromuscular dysplasia for 5.4%. Oral contraceptives were involved in the hypertension of 19% of the females.

Management of resistant hypertension: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology.

To improve the management of resistant hypertension, the French Society of Hypertension, an affiliate of the French Society of Cardiology, has published a set of eleven recommendations. The primary objective is to provide the most up-to-date information based on the strongest scientific rationale and that is easily applicable to daily clinical practice. Resistant hypertension is defined as uncontrolled blood pressure on office measurements and confirmed by out-of-office measurements despite a therapeutic strategy comprising appropriate lifestyle and dietary measures and the concurrent use of three antihypertensive agents including a thiazide diuretic, a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, for at least 4 weeks, at optimal doses. Treatment compliance must be closely monitored, as must factors that are likely to affect treatment resistance (excessive dietary salt intake, alcohol, depression, drug interactions and vasopressor drugs). If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for potential target organ damage and secondary causes of hypertension. The recommended treatment regimen is a combination therapy comprising four treatment classes, including spironolactone (12.5-25 mg per day). In the event of a contraindication or a non-response to spironolactone, or if adverse effects occur, a ß-blocker, an α-blocker, or a centrally acting antihypertensive drug should be prescribed. Because renal denervation is still undergoing assessment for the treatment of hypertension, this technique should only be prescribed by a specialist hypertension clinic.

[Place of clinical pharmacist in the management of drugs in patients with hypertension]. / Place du pharmacien clinicien dans la prise en charge thérapeutique du patient hypertendu.

PURPOSE: To synthesize pharmacists' interventions made in the department of internal medicine and hypertension of university hospital of Toulouse and assess the impact on medication orders. METHODS: This is a single-center, prospective study using pharmacists' interventions recorded between September 2013 and March 2014 on the Act-IP(©) website of the French Society of Clinical Pharmacy. The clinical pharmacist is present everyday in the unit to establish the medication reconciliation of new patients (the process of comparing a patient's medication orders to all of the medications that the patient has been taking), and analysis of medication orders. When a risk of iatrogenic drug is identified, a therapeutic change is proposed to the prescriber. RESULTS: A total of 2491 medication orders were analyzed for 7 months, leading to 39 pharmacists' interventions (1.6 pharmacists' interventions per 100 medication orders). The most commonly identified drug-related problems were improper administration (33%, n=13), not prescribed drug (21%, n=8), non-conformity to guidelines (18%, n=7), supratherapeutic dose (15%, n=6), and 13% (n=5) targeted prescribed treatment not administered, underdosing, incorrect administration or drug interaction. The most relevant molecules were atorvastatin (10%), bromazepam (8%) and levothyroxine (8%) and only 2 interventions targeted antihypertensive drugs. The rate of physicians' acceptance was 92%. CONCLUSION: Pharmacists' interventions mainly concern the co-prescriptions of antihypertensive drugs and very few antihypertensive drugs. The clinical pharmacist contributes to preventing iatrogenic in patients with hypertension with a very good acceptance by the clinician.

Effect of postural changes on aldosterone to plasma renin ratio in patients with suspected secondary hypertension.

AIMS: To study the influence of postural changes on aldosterone to renin ratio (ARR) in patients with suspected secondary hypertension and to evaluate the sensitivity and specificity of the recommended seated ARR compared to supine and upright ARR for primary aldosteronism screening. METHODS: Fifty-three hypertensive patients were prospectively hospitalized for secondary hypertension exploration (age: 51 ± 12, 66% males). After withdrawal of drugs interfering with renin angiotensin system, plasma aldosterone and direct renin concentration were measured in the morning, at bed after an overnight supine position, then out of bed after 1 hour of upright position and finally 2 hours later after 15 minutes of seating. Minimal renin value was set at 5 µUI/mL. RESULTS: Referring to ARR cut-off of 23 pg/µUI, the sensitivity of seated ARR was 57.1% and specificity was 92.3%. The negative and positive predictive values were 95.1% and 45.2% respectively. Compared to these results, a cut-off of 19 improved sensitivity to 85.7% with a specificity of 89.7%. Negative and positive predictive values were 98.3% and 41.1% respectively. Seated ARR mean value was lower than supine and upright ARR mean values, due to an overall increase in renin at seating compared to the supine position by factor 1.9 while aldosterone just slightly increased by factor 1.2. Seated ARR correlated to supine and upright ARR: correlation coefficients (r) 0.90 and 0.93 respectively (P<0.001). CONCLUSIONS: Current recommended measurement of ARR in the seating position is fairly correlated to supine and upright ARR. A suggested cut-off value of 19 instead of 23 pg/µUI increased the discriminating power of this test.

Orthostatic hypotension is associated with more severe hypertension in elderly autonomous diabetic patients from the French Gerodiab study at inclusion.

UNLABELLED: Orthostatic hypotension (OH) has deleterious effects on patients' cardiovascular prognoses. The combination of increased age and diabetes adds to the risk of OH. The aim of the study was to describe the elderly diabetic population relative to the degree of hypertension, the occurrence of complications, medications and cognitive function. METHODS: In the Gerodiab study (a 5-year French multicentre, prospective, observational study), a total of 987 type 2 diabetic autonomous patients, aged 77±5 years, were recruited between June 2009 and July 2010. Clinical blood pressure measurements were taken supine and then after 1, 3 and 5minutes in a standing position. OH was defined as a decrease in systolic blood pressure (SBP) of at least 20mmHg and/or a decrease in diastolic blood pressure (DBP) of at least 10mmHg at any of the measurements while standing. RESULTS: At inclusion 301 (30.5%) patients had OH; SBP and DBP at rest were higher in patients with OH than in those without (146±21/78±11mmHg vs. 138±17/72±10mmHg; P<0.001). Individuals with OH exhibited higher pulse pressure (PP) than individuals without (68±18 vs. 65±15mmHg; P<0.05). A significant increase in waist-to-hip ratio was recorded in those with OH versus patients without (P<0.01). Despite more severe hypertension (SBP>160mmHg at inclusion; P<0.01), no significant difference was recorded in the mean number of antihypertensive drugs (1.7±1.1), or in the class of antihypertensive drugs, including beta-blockers (P=0.19) and diuretics (P=0.84). Patients with OH were more likely to have a history of peripheral arterial disease and amputations (31% vs. 24%, P<0.05, and 3.3% vs. 1.5%, P=0.056). There was no significant association between OH and history of peripheral neuropathy (P=0.37), stroke, heart failure or ischemic heart disease. In multivariate analysis, OH remained associated with severe hypertension (P<0.01), increased waist-to-hip ratio (P<0.05) and amputations (P<0.05). CONCLUSION: About one-third of elderly, autonomous diabetic patients had OH. They had more severe hypertension, with higher SBP, DBP and PP at rest. However, the number of anti-hypertensive drugs did not differ compared to patients without OH. This could reflect the medical teams' fears about intensifying treatment.

Is it useful to repeat an adrenal venous sampling in patients with primary hyperaldosteronism?

UNLABELLED: Adrenal venous sampling (AVS) is a challenging technical procedure and few patients had AVS procedure twice. AIM: To evaluate the reproducibility of the AVS, why AVS were repeated and the conclusions drawn from them. PATIENTS AND METHODS: From 1997-2012, 12 patients underwent two AVS. A cortisol level in the adrenal vein greater than or equal to 1.1 to inferior vena cava defined a successful catheterization and a lateralization of secretion corresponded to an aldosterone-to-cortisol vein ratio greater than or equal to 2 between the one side to another. RESULTS: The same side of lateralization of secretion was found in 75% of them. The second AVS were due to technical failure (n=4), unproven lateralization (n=2), a lateralization opposite to the main nodule and ipsilateral to hyperplasia (n=4) on first AVS. For two patients, as the CT was normal, AVS was required again. The second AVS was successful in all patients, including those with an initial technical failure but only patient with technical failure underwent surgery, as BP and kaliemia were controlled. Lateralization on the side of hyperplasia or opposite to the biggest nodule was confirmed in two of four cases. CONCLUSION: When AVS is unsuccessful for technical reasons, it is worth doing it again but after being sure that surgery is still possibly indicated.

Evaluation of oral health related to body mass index.

OBJECTIVE: Poor oral health has previously been related to high body mass index (BMI). We aimed at exploring the link between BMI and several oral health markers, after adjustment for dietary patterns and plasma insulin, both of which could act as mediators. SUBJECTS AND METHODS: Dental examination was performed in a sample of 186 French subjects aged 35-64 years and selected from the general population to assess number of missing teeth, periodontitis, clinical attachment loss (CAL), probing pocket depth (PD), gingival index (GI) and plaque index (PI). Data collection also included a food-frequency questionnaire. BMI (considered as outcome variable) was categorized into quartiles, and as BMI<25; 25 ≤BMI<30; and BMI ≥ 30 kg m(-2) . RESULTS: After adjustment for age, gender, education level, smoking, physical activity, energy intake and C-reactive protein, BMI was statistically associated with missing teeth, PD and PI, but not with CAL, GI or periodontitis. After additional adjustment for 'high-carbohydrate' diet and plasma insulin or HOMA (homeostasis model assessment) index for insulin resistance, the statistical relationship between BMI and oral variables remained significant only for PD and PI. CONCLUSIONS: Plaque index, reflecting dental plaque, and PD, closely linked with periodontal inflammation and infection, are statistically associated with high BMI and obesity, independently of dietary patterns and insulin resistance.

Prognostic value of nocturnal blood pressure and reverse-dipping status on the occurrence of cardiovascular events in hypertensive diabetic patients.

AIM: To assess whether reverse-dipping status is associated with cardiovascular (CV) events such as CV death, myocardial infarction (MI) or stroke in diabetic patients with hypertension. METHODS: A total of 97 diabetic patients underwent their first ambulatory blood pressure monitoring (ABPM 1). "Reverse dippers" were defined as patients with a nighttime systolic and/or diastolic blood pressure (BP) greater than daytime systolic and/or diastolic BP. Other patients were called "others". A second ABPM (ABPM 2) was done after a median delay of 2.6 years. Patients were then followed for a further 2.9-year median period (total median follow-up: 5.5 years). RESULTS: After ABPM 1, CV events occurred in 53% of the reverse dippers (n=15) and in 29% of the others (n=82). Kaplan-Meier curves showed significant differences between the two groups (P=0.003). Mean nighttime systolic BP on ABPM 1 was 148+/-23 mmHg and 142+/-19 mmHg in patients who did and did not experience a CV event, respectively. With Cox analysis adjusted for confounders, a 10 mmHg increase in nighttime systolic BP was associated with a 35% increase in the risk of a CV event (hazard ratio [HR]: 1.35, P=0.003). The HR for a CV event in reverse- versus nonreverse-dipping status was 2.79 (P=0.023). After ABPM 2, the relationship between the reverse-dipping status and occurrence of CV events was no longer evident (P=0.678). Nighttime systolic BP remained predictive of CV events (P=0.001). CONCLUSION: These findings suggest that nighttime systolic BP per se appeared to be a stronger predictor of an excess risk of CV events compared with reverse-dipping status.

Prevention of progression to dementia in the elderly: rationale and proposal for a health-promoting memory consultation (an IANA Task Force).

Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

Should pulse pressure and day/night variations in blood pressure be seen as independent risk factors requiring correction or simply as markers to be taken into account when evaluating overall vascular risk?

Patients with a blunted fall in nocturnal BP (known as non-dippers) have a high risk of micro- and macrovascular complications, particularly if they have hypertension, but also in normotensive patients with diabetes. A blunted fall in nocturnal BP reflects the high level of CV risk in these patients. ABPM data indicating an altered circadian BP rhythm reverse circadian BP profile should alert the physician to the potential risk of complications and should lead to efforts to treat hypertension effectively, especially at night, and to check for sleep apnoea syndrome, particularly in cases of resistant hypertension, or autonomic neuropathy (postural hypotension), a well known risk factor for cardiovascular (CV) events. Patients should be carefully screened for nephropathy. However, the definitions of "non-dipper" vary widely. Suitable treatments are poorly defined, but angiotensin-converting enzyme inhibitors (ACEi), diuretics, salt restriction and the maintenance of continuous positive airway pressure (CPAP) can be used as non-specific treatments. The efficacy of taking blood pressure-lowering drugs at bedtime rather than in the morning is still debated but deserves attention. In the diabetic population, brachial pulse pressure (PP) is an independent predictor of cardiovascular mortality, but not of all-cause mortality. It is also associated with complications of both type 2 and type 1 diabetes, this effect being stronger for nocturnal than for diurnal PP, and is strongly predictive of coronary heart disease in patients with type 2 diabetes. The stronger association between PP and age in diabetic than in non-diabetic populations suggests that diabetes accelerates vascular ageing. In patients with incipient nephropathy or overt renal failure, PP increases CV risk. However, misinterpretation could be related to confusion between brachial PP and central PP. The therapeutic implications of PP measurement remain poorly documented in diabetes.

[French as 2005-recommendations on the management of arterial hypertension]. / Les recommandations HAS 2005(1) sur la prise en charge des adultes atteints d'hypertension artérielle quelles nouveautés?

Self blood pressure measurements (home BP) and/or ambulatory BP measurements are recommended in mild to moderate hypertension (140/90 - 179/109 mmHg) in order to confirm sustained hypertension and identify white coat and masked hypertension. The evaluation of target organ damages (TOD) has to be integrated in cardiovascular risk estimate and taken into account in the management of hypertensive patients. Beside echocardiography, there is a place for the screening of microalbuminuria in non diabetic hypertensive patients, but these investigations should not be performed systematically. Arterial stiffness evaluation and carotid intima-media thickness quantification are not yet recommended. Cardiovascular risk (CV risk) estimate plays a pivotal role in the therapeutic decision and strategy. The cardiovascular risk grade is based on [1] the list of cardiovascular risk factors (same list AFSSAPS recommendations on dyslipidemia), [2] the presence or absence of TOD and [3] cardiovascular complications: "low", "medium", and "high" CV risk. Lifestyle modifications are recommended in all hypertensive patients. Five antihypertensive drugs are recommended for first line therapy: beta-blockers, thiazide diuretics, ACEIs, ARA II and CCBs (and fixed low dose combinations with AFSSAPS agreement for first line). In order to initiate the treatment, Evidence-based therapy (according to clinical trials conducted in different clinical situations), certain comorbid conditions (compelling indications), efficacy and side-effects in a previous experience, and the cost are the determinants of the first choice. Most hypertensive patients require more than one agent to achieve target blood pressure and for second line therapy the recommended combinations are: betablockers-diuretics, ACEIs-diuretics, ARAII-diuretics, betablockers-CCBs (DHP), ACEIs-CCBs, ARA II-CCBs and CCBs-diuretics. The delay to establish a combination therapy depend on CV risk. The BP goals are those recommended by ESH-ESC 2003: BP<140/90 mmHg in all, BP<130/80 mmHg in diabetic patients and in patients with chronic renal failure. Beside lowering BP, the reduction in proteinuria <500 mg/24 h is a new goal in these high risk patients. These guidelines provide a tool for every day practice and applicability should be evaluated.

[The best of hypertension in 2006]. / L'essentiel de 2006 en hypertension artérielle.

The TROPHY study was designed to show the feasibility of pharmacological prevention of hypertension with respect to the group of patients with "prehypertension" as defined by the JNC VII recommendations. This clinical trial compared candesartan 16 mg/day with placebo and the result at 4 years was a reduction in the relative risk of developing hypertension of 15.6%. The antihypertensive drug delayed the onset of hypertension in a mainly overweight masculine population. Staessen, Zhu and O'Brien's groups suggest measuring an index of arterial rigidity obtained from ambulatory blood pressure monitoring: the ambulatory arterial stiffness index (AASI). This is calculated as [1- slope of systolic/diastolic pressure]. The reference values for AASI vary with age from 0.50 to 0.70. The CAFE study, a spin-off of the ASCOT trial, showed that the central blood pressure decreased more than the peripheral blood pressure with the association amlodipine-perindopril as compared with atenolol and a thiazide diuretic. The capacity of an antihypertensive drug or an association of antihypertensives to decrease the central blood pressure could be a pertinent factor of evaluation to be taken into account in the interpretation of clinical trials. The study of the Italian cohort PAMELA showed a progressive increase in cardiovascular and global mortality with respect to the findings of increased blood pressure by one, two or three methods of measurement (at the office, at home, ambulatory) compared with patients declared normotensive by the same methods. This registry confirmed the implication of masked hypertension on cardiovascular prognosis and also showed that "white coat" hypertension was not completely benign. The "3 cities" study is a French epidemiological study of persons over 65 years of age. The control of the blood pressure of the treated elderly hypertensives was 57% in men and 70% in women when the cut-off was 160/95 mmHg and 31% for all patients in a cut-off level of 140/90 mmHg. Lafontan et al. are studying the mobilisation of fat induced by exercise, resistant to betablockers therapy and attributed to natriuretic peptides. This metabolic pathway could be of relevance in the metabolic syndrome and in cardiac failure. Renin inhibitors, such as aliskiren, are being developed. The outlook is the possible use of these drugs with ACE inhibitors or angiotensin II inhibitors, taking into account the risk/benefit ratio.

Association of eNOS Glu298Asp gene polymorphism with circadian blood pressure rhythm.

Hypertensive patients with altered circadian blood pressure (BP) profile experience greater repercussion of hypertension on target organs and a higher risk of cardiovascular events, compared with those with physiological variations in BP. It has been demonstrated in animal models, that circadian variations in BP depend on several regulatory systems, in particular the nitric oxide-cGMP pathway. eNOS298 Glu/Asp polymorphism is a functional variant and may alter the amount of NO generated or eNOS activity. The objective of the present study was to find out whether eNOS298 gene polymorphism affects circadian BP regulation in 110 healthy subjects and 155 never-treated hypertensive patients recruited at Hypertension Units in Grenoble, Toulouse and Lille (France).