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Background/Aim: Prescription guidelines caution against chronic benzodiazepine (BZD) use. Nevertheless, chronic use among older adults, especially in nursing homes is widespread. We wanted to explore why it is difficult to implement discontinuation. We focused on individual residents that used BZDs and explored benefit and harm of chronic BZD use, willingness to try and barriers against the discontinuation of chronic BZD use. Methods: In this cross-sectional study, we selected nursing home residents with at least 3 months of BZD use. A resident-specific questionnaire was addressed to the GP and to the responsible nurse and questioned effectiveness, side effects, initiation and willingness to stop. For every resident, the GP and nurse had to score 8 barrier statements on a 10-point Likert scale. Additionally, we collected 10 general attitudes scored by GPs and nurses. Results: We received data for 109 chronic BZD users. GPs and nurses indicated that the BZD still had the desired effect in respectively 87% and 83% of the 109 residents and in 75% and 70% they observed no sideeffect. Dependence was seen in respectively 41% and 28%. Overall, the GPs had higher barriers than the nurses but indicated a higher willingness to stop (33% vs. 21%). Both caregivers were willing to stop in 13% of the residents. Conclusion: The perceived effectiveness, the absence of side-effects and the presence of dependence in most residents on chronic BZD use resulted in a low willingness to stop. Future discontinuation guidelines should consider all caregivers' perceptions and promote a multidisciplinary approach. (C) 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.

Summary What is known and objective Sunitinib, a CYP3A4 substrate, is standard of care treatment in metastatic renal cell carcinoma (mRCC) and is administered orally as a single dose of 50 mg, in a 4 weeks on/2 weeks off regimen. Frequently, dose reduction is necessary because of toxicity, as is the association of comedication to treat side effects. In addition, existing comorbidities in these patients necessitate the intake of various classes of chronic medication. Only limited data are available on the risk of drug–drug interactions (DDI). The objective of our paper was to evaluate prescribed dose, comedication, risk of drug–drug interactions and outcome among patients with mRCC treated with sunitinib. Methods A single-centre, retrospective analysis was performed for patients with mRCC treated with sunitinib. The drug interaction databases ‘Clinical Pharmacology’© and ‘Lexicomp’© were used to screen for possible interactions. Results and discussion The hospital files of 36 patients with mRCC were evaluated. Twenty-two patients received sunitinib as first-line treatment. Progression-free survival (PFS) in this first-line group was longer for patients that started with full-dose sunitinib (21·1 months; n = 12) than for patients started on reduced dose (3·5 months; n = 10). In the whole group of 36 patients, an average of 6·8 comedications was taken. Possible pharmacodynamic drug–drug interactions were most frequently found (47%) and reported as major interactions (QT prolongation). Risk of pharmacokinetic interactions due to co-administration of CYP inhibitors, CYP inducers, CYP substrates and PgP substrates was reported for 8%, 11%, 53% and 19%, respectively. These interactions were reported as major or moderate. What is new and conclusion Patients with mRCC under treatment with sunitinib at a reduced starting dose had a decreased PFS compared with patients started with full-dose sunitinib. Due to adverse drug reactions and comorbidity, patients under sunitinib, a CYP3A4 substrate, took an average of 6·8 comedications provoking an important risk of major-to-moderate drug–drug interactions. With the help of a multidisciplinary team, avoidance of drug–drug interactions could be obtained. Moreover, serial ECG monitoring is recommended for patients at high risk of QT prolongation.

Introduction: Assessing arterial and haemodynamic properties in response to a physiological perturbation might provide additional information on an individual's "vascular health". The aim of this study was to assess the feasibility of measuring changes in carotid stiffness and haemodynamics in response to sympathetic nervous system stressors, such as the Hand Grip Test (HGT) and the Cold Pressor Test (CPT). Methods: A non-invasive protocol, consisting of two HGT's at 30% and 40% of maximal voluntary contraction and a CPT, was performed in 12 young healthy volunteers (6 males/6 females). Measurements included continuous finger blood pressure recordings (NexFin; non-dominant hand) and ultrasound measurement of common carotid diameter distension and flow velocity at discrete moments in time during the protocol (GE Vivid 7 system). Carotid distension (δD/D), local wave speed using the waterhammer equation (PWVWH) and reflection magnitude (RM; ratio of backward to forward diameter wave) were derived from the data. Results: Consistent with the overall increase in blood pressure, carotid diameter increased while δD/D decreased. PWVWH and RM showed high variability during both HGT's and CPT. Conclusion: It is feasible to monitor the carotid haemodynamic response to selected sympathetic nervous system stimulus. Moreover, the analysis showed supporting evidence of specific physiological response to regulate adequately each stress stimulus.

Background: Antipsychotic use for behavioural and psychological symptoms of dementia (BPSD) is controversial. Guidelines advise to reduce antipsychotics given the adverse effects and limited efficacy, to limit dose and treatment duration as well as to undertake discontinuation. Methods: A pilot study with 40 hospitalised geriatric cognitively impaired patients, in which the effects of abrupt antipsychotic discontinuation were investigated, using neuropsychiatric inventory (NPI) scores before and one month after discontinuation. Withdrawal symptoms were monitored thrice a day with a checklist during five consecutive days. Results: Participants (n¼40) had a mean age of 84 years (range 6795) and 53% were male. The total mean baseline NPI score was 21 (SD 12) with predominantly behavioural rather than psychological disturbances. After abrupt discontinuation, mild withdrawal symptoms were observed in 72% of the patients, with frequencies of symptoms peaking on day 2 (53%) and day 3 (48%). After one month, 31 patients (85%) were still off antipsychotics and improved on the majority of NPI domains, with a total mean NPI score decreasing from 18 (SD 13) to 12 (SD 8, p¼0.003). In the relapse group, there was no deterioration associated with the abrupt discontinuation and subsequent resumption of therapy with a total mean NPI score decreasing from 31 (SD 12) at baseline to 27 (SD 8) at one-month follow-up (p¼0.345). Conclusion: Abrupt antipsychotic discontinuation appears to be feasible in older individuals with BPSD. Systematically performed discontinuation efforts in clinical practice are needed to differentiate between patients where antipsychotics have no added value and patients where the benefits outweigh the risks.

Objective : To describe medication management among home-dwelling older adults. These data should allow us to identify potential problems and to indicate target areas for community pharmacist intervention. Design : Cross-sectional observational study. Setting : Community pharmacies (n=86) in Belgium. Participants : Home-dwelling older adults using at least one chronic medicine (n=338). Measurements : Data on drug use were taken from the electronic pharmacy databases, while drug adherence was measured by pill count, self-report and estimation by GP and pharmacist. Drug knowledge and practical drug management capacity were assessed by patient interview and questionnaire, respectively. Results : The study population (n=338) used a median of 5 chronic drugs per patient. Half of our sample (n=169) used psychotropic medication chronically, mainly benzodiazepines. In 100 patients (29.6%) at least one drug-drug interaction of potential clinical significance was observed. The overall mean adherence per patient was very high (98.1%), but 39.6% of individuals was underadherent with at least one medication. Seventy-six % of patients had an acceptable knowledge of the indication for at least 75% of their medication. In nearly 15 % of the study population cognitive impairment was suspected by the Mini-Cog Test. The participants reported several practical problems with drug taking; difficulties with vision (32.0%), blister opening (12.1%), tablet swallowing (14.8%), tablet splitting (29.7% [represents % of patients who have to split tablets]) and distinction between different drug packages (23.4%). Conclusion : This study identified the following aspects of medication management by home-dwelling older adults that could be improved by pharmaceutical care sendces; (i) assistance of cognitively impaired patients, (ii) management of practical drug taking problems, (iii) DDI screening, (iv) drug adherence, and (v) chronic benzodiazepine use.

Background: This observational community pharmacy-based study aimed to investigate headache characteristics and medication use of persons with regular headache presenting for self-medication. Methods: Participants (n = 1205) completed (i) a questionnaire to assess current headache medication and previous physician diagnosis, (ii) the ID Migraine Screener (ID-M), and (iii) the Migraine Disability Assessment questionnaire. Results: Forty-four percentage of the study population (n = 528) did not have a physician diagnosis of their headache, and 225 of them (225/528, 42.6%) were found to be ID-M positive. The most commonly used acute headache drugs were paracetamol (used by 62% of the study population), NSAIDs (39%), and combination analgesics (36%). Only 12% of patients physician-diagnosed with migraine used prophylactic migraine medication, and 25% used triptans. About 24% of our sample (n = 292) chronically overused acute medication, which was combination analgesic overuse (n = 166), simple analgesic overuse (n = 130), triptan overuse (n = 19), ergot overuse (n = 6), and opioid overuse (n = 5). Only 14.5% was ever advised to limit intake frequency of acute headache treatments. Conclusions: This study identified underdiagnosis of migraine, low use of migraine prophylaxis and triptans, and high prevalence of medication overuse amongst subjects seeking self-medication for regular headache. Community pharmacists have a strategic position in education and referral of these self-medicating headache patients.

Using the Sphygmocor device it is recommended that the radial pressure wave is calibrated for brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP). However it has been suggested that brachial-to-radial pressure amplification causes underestimation of central blood pressures (BPs) using this calibration. In the present study we examined if different calibrations had an impact on estimates of central BPs and on the clinical interpretation of our results. On the basis of ambulatory BP measurements, patients were categorized into patients with controlled, uncontrolled or resistant hypertension. We first calibrated the radial pressure wave as recommended and afterwards recalibrated the same pressure wave using brachial DBP and calculated mean arterial pressure. Recalibration of the pressure wave generated significantly higher estimates of central SBP (P=0.0003 and P

Summary What is known and Objective: There is little evidence from well-designed randomized controlled trials of the impact of community pharmacist intervention on the clinical management of patients with type 2 diabetes. It is also not known how sustainable any observed effects on glycaemic control are, over time. This study was initiated to address both these issues. Methods: A 6-month, randomized, controlled parallel-group trial in 66 community pharmacies was conducted in Belgium. Patients were randomly assigned to receive usual pharmacist care (n = 135) or a predefined pharmacist intervention (n = 153). The intervention mainly focused on correct medication use, medication adherence and healthy lifestyle promotion. Primary outcome was glycaemic control, as measured by fasting plasma glucose and HbA1c. Sustainability of changes in glycaemic control was assessed by additional glucose measurements 18 months after the end of the study. Results and Discussion: The intervention significantly reduced HbA1c (between-group difference: 0·5%, P = 0.009). The largest impact on HbA1c was observed when pharmacotherapy changes (i.e., type and/or dose of hypoglycaemic agents) initiated by the physician were sustained with pharmaceutical care: HbA1c was reduced by 1·05% in the intervention group, whose medication was changed, compared with a reduction of 0·02% in the therapy-modification only, group. It was also found that the diabetes education program resulted in improved self-management and better knowledge of diabetes. Eighteen months after the end of the formal study period, the mean HbA1c of the intervention group did not differ significantly from the control group (7·4% vs. 7·2%). What is new and Conclusion: This study provides new evidence, from a randomized controlled trial, of the beneficial effect of community pharmacist intervention in the clinical management of type 2 diabetic patients. However, questions remain about the sustainability of the observed improvements.

Vaginal delivery of 200 mg or 25 mg dapivirine from intravaginal rings (IVRs) was evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008, respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was generally safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Across both studies, dapivirine concentrations in vaginal fluids measured at the introitus, cervix, and ring area were within the mean range of 0.7-7.1 microg/ml. Mean dapivirine concentrations in vaginal and cervical tissues on day 7 were 0.3-0.7 microg/g in IPM001 and 1.5-3.5 microg/g in IPM008. Mean plasma concentrations of dapivirine were50 pg/ml. Dapivirine from both IVRs was successfully distributed throughout the lower genital tract at concentrations1000x the EC(50) against wild-type HIV-1 (LAI) in MT4 cells suggesting that IVR delivery of microbicides is a viable option meriting further study.

Quinine sulphate (QS), like most other antimalarials, is in tablet form designed for adults. In children, treatment is based on breaking the tablets to adapt the dose to the child's bodyweight. However, poor breakability owing to the tablet design or the absence of a score line can lead to inaccurate dosage. Furthermore, QS is very bitter which reduces its acceptability to children. QS taste-masked pellets have been developed which offer more flexibility in adapting dosage to a child's weight.To evaluate the oral bio-availability of QS taste-masked pellets in healthy adult volunteers and to determine steady-state plasma concentrations in children aged5 years with uncomplicated Plasmodium falciparum malaria.Healthy adult volunteers at Kigali University Hospital received a single dose of 600 mg QS as taste-masked pellets or as commercially available tablets. A total of 56 children5 years with uncomplicated P. falciparum malaria were recruited among patients attending Butare University Hospital and nearby health centres and treated with QS taste-masked pellets, 10-12.5 mg/kg every 8 h for 7 days. Quinine steady-state plasma concentrations were assessed on the 4th day of treatment.Following administration of taste-masked pellets to healthy adult volunteers, peak plasma concentration (C(max)) and area-under-the-curve (AUC) (C(max) 4.7 microg x ml(-1), AUC(0-24) 63.5 microg x h x ml(-1)) were significantly higher (p0.05) than for tablets (C(max) 3.7 microg x ml(-1), AUC(0-24) 52.4 microg x h x ml(-1)), but still within the limits reported for quinine. The steady-state concentrations in children were in the therapeutic range for quinine. All the children recovered and completed the 14-day follow-up.QS taste-masked pellets offered the possibility to easily adjust the dose to the bodyweight of the child and can be used as an alternative to dividing tablets.

Objective This study was performed to determine whether students who are trained in developing a personal formulary become more competent in rational prescribing than students who have only learned to use existing formularies. Methods This was a multicentre, randomised, controlled study conducted in eight universities in India, Indonesia, the Netherlands, the Russian Federation, Slovakia, South Africa, Spain and Yemen. Five hundred and eighty-three medical students were randomised into three groups: the personal formulary group (PF; 94), the existing formulary group (EF; 98) and the control group (C; 191). The PF group was taught how to develop and use a personal formulary, whereas e the EF group was taught how to review and use an existing formulary. The C group received no additional training and participated only in the tests. Student’s prescribing skills were measured by scoring their treatment plans for written patient cases. Results The mean PF group score increased by 23% compared with 19% for the EF group (p

Summary The aim of this study was to describe medication use and disease management of asthmatic patients and to evaluate the usefulness of the Asthma Control Test (ACT) in community pharmacies. In 54 Flemish community pharmacies 166 asthmatic patients were included in the study. At inclusion, the study persons completed a survey to assess subject characteristics, symptoms and asthma attacks, and peak expiratory flow (PEF) was measured. Furthermore, the actual level of asthma control was assessed by ACT, a clinically validated measure of asthma control. Prescribed medicine data of the patients were 1 year retrospectively analysed from the prescriptions. Mean age of the sample was 36.8 year, 23% were smokers. As maintenance treatment, 63% of the patients used a combination product containing an inhaled corticosteroid and a long-acting β 2 -agonist in a single inhaler. According to ACT, 49.1% of the patients were insufficiently controlled. Only 4.9% of the patients had a maximal ACT score of 25, indicating complete asthma control; 46.0% of the study population obtained an ACT score between 20 and 24, meaning that their asthma is well controlled. In contrast, 30.7% of the patients had a score between 15 and 19, indicating uncontrolled asthma. In all, 18.4% obtained ACT scores of less than 15, meaning that their asthma was seriously out of control and necessitating referral to their general practitioner or lung specialist. Importantly, the correlation between the self-perceived level of asthma control and the objective assessment of the asthma control level was poor: 82.3% of the patients believed their asthma to be totally or well controlled, while this was the fact for only 50.9% of the patients. In conclusion, the ACT appears to be a useful tool to determine rapidly and accurately the level of asthma control in patients presenting at community pharmacies.

Early return of reflected pressure waves increases the load on central arteries and may increase the risk of aortic rupture in patients with Marfan's syndrome (MFS). To assess whether wave reflection is elevated in MFS, we used ultrasound and MRI to measure central pressure and flow waveforms in 26 patients (13–54 yr of age) and 26 age- and gender-matched controls. Aortic systolic and diastolic cross-sectional areas were measured at the ascending and descending aorta (AA and DA), diaphragm (DIA), and lower abdominal aorta (AB). From these measurements, local characteristic impedance ( Z0- xx) and local reflection coefficients (Γ xx-yy) were calculated. Calculated global wave reflection indexes were the augmentation index (AIx) and the ratio of backward to forward pressure wave (Pb/Pf). The aorta was wider in MFS patients at AA ( P < 0.01) and DA ( P < 0.01). Aortic pulse wave velocity was 42 cm/s higher in MFS patients ( P < 0.05). Z0- xx was not different between groups, except at DA, where it was lower in MFS patients. In controls, ΓAA-DA was 0.31 ± 0.08, ΓDA-DIA was 0.00 ± 0.11, and ΓDIA-AB was 0.31 ± 0.16. Mean values of Γ xx-yy were not different between MFS patients and controls. In controls, aging diminished ΓAA-DA but increased ΓDIA-AB. Clear age-related patterns were absent in MFS patients. AIx or Pb/Pf was not higher in MFS patients than in controls. There were indications for enhanced wave reflection in young MFS patients. Our data demonstrated that the major determinants of AIx were pulse wave velocity and the effective length of the arterial system and, to a lesser degree, HR and Pb/Pf.

This review addresses the pharmacotherapy of antidepressants in the elderly. We performed a search based on Medline and the Cochrane Library. In addition to a meta-analysis of 17 randomised controlled studies, 36 randomised controlled trials of patients over the age of 60 published between 1980 and 2005 in English met the selection criteria and were included. Existing evidence suggests that no one class of antidepressant drugs has been found to be more effective than another in the treatment of depression in the elderly. Although newer antidepressants are not more effective than older ones, they are better tolerated and are safe especially in overdose. The adverse effect data suggest modest superiority of selective serotonin reuptake inhibitors over tricyclic antidepressants. The evidence available indicates that antidepressant treatment of four weeks has a beneficial effect compared to placebo. As to prevention of relapse and recurrence, antidepressants should be continued for at least six months after good initial response. In patients with high risk of relapse, treatment should be continued for at least two years. Long-term efficacy has been shown for dosulepin, nortriptyline and citalopram. In patients with dementia with persistent and significant symptoms antidepressant treatment may be indicated. At present, clomipramine, citalopram and sertraline have been reported as being superior to placebo. There is a paucity of data on the use of antidepressants in very elderly individuals, patients with significant comorbidity and patients with dementia. More data on the effect of antidepressants in the elderly, especially in the over 80-age group are needed.

Providing factual data about non-communicable diseases (NCDs) is of utmost importance in the sub-Saharan African countries where NCDs and arterial hypertension data remain scattered, scarce, and less representative given the region's heterogeneous population. Within this context, the interuniversity cooperation VLIR-UOS/Catholic University of Bukavu (Democratic Republic of Congo) has established an integrated project for monitoring hypertension and cardiovascular risk factors in the population of South Kivu. The aim of the study was to present the basic results of the determinants of blood pressure in the cohort studied.In 2013 and 2014, trained interviewers collected the anthropometric parameters, blood pressure, and medical history of 7405 adults (3060 in urban areas and 4345 in rural areas) including 3162 males and 4243 females; the cohort is expected to be followed for 9 years.The average age of the entire group was 33.0±16.7 years. Compared to men, women had significantly higher obesity indices (P0.0001), lower blood pressure between 20 and 39 years of age (P0.0001) but higher blood pressure at 60 years of age and older (P0.0001). Blood pressure was positively correlated with body mass index, waist circumference, and paradoxically with consumption of vegetables, but negatively correlated with the consumption of fruit, intense physical activity, and relaxation at home.These results show that a cohort study is feasible in the Democratic Republic of Congo. The factual data analysis can contribute to health policy orientation and setting up of preventive measures. Since most correlated risk factors are preventable, recommendations can already be made in the fight against high blood pressure in this population.

No longitudinal study addressed whether systolic blood pressure level (SBPL) or within-visit variability (SBPV) predict arterial properties or vice versa. In families randomly recruited from a Flemish population, we determined SBPL and SBPV from five consecutive blood pressure readings. The indexes of SBPV were variability independent of the mean, the difference between maximum and minimum SBPL, and average real variability. We measured carotid intima-media thickness and distensibility by ultrasound and carotid-femoral pulse wave velocity by tonometry (SphygmoCor, version 8.2). Effect sizes were computed for 1-s.d. increments in the predictors, while accounting for covariables and family clusters. Among 1087 participants (50.4% women; mean age, 41.8 years), followed up for 2.55 years (median), higher SBPL predicted (P0.019) higher carotid intima-media thickness (+15 μm), lower carotid distensibility (-1.53 10(-3) kPa(-1)) and faster carotid-femoral pulse wave velocity (+0.285 m s(-1)) at follow-up, whereas none of the SBPV indexes predicted the arterial traits at follow-up (P0.11). In a subset of 713 participants, followed up for another 3.14 years, lower carotid distensibility predicted (P

Contains fulltext : 81348.pdf (Publisher’s version ) (Closed access) Recent position papers addressing the profession of clinical pharmacology have expressed concerns about the decline of interest in the field among clinicians and medical educators in the United Kingdom and other Western countries, whether clinical pharmacology is actually therapeutics, and whether the profession should be limited to physicians. The Dutch Society for Clinical Pharmacology and Biopharmacy offers answers to these questions and presents a new model for clinical pharmacology.

Objectives: To compare quality of life with the selective β1-blocker bisoprolol and the thiazide diuretic bendrofluazide in patients with mild to moderate hypertension. Design and setting: Multi centric, randomised, double-blind, two-way crossover study carried out at six general practice centres. Subjects: Eighty-one patients with newly diagnosed or previously treated hypertension, who had a mean diastolic blood pressure (BP) of 95–120 mm Hg after receiving placebo for 4–6 weeks. Interventions: In random order, patients received bisoprolol (5 mg once daily) or bendrofluazide (2.5 mg once daily) for 8 weeks. Main outcome measures: Quality of life and antihypertensive effect. Results: Decrease in systolic/diastolic BP did not differ between bisoprolol (10 ± 2/13 ± 1 mm Hg) and bendrofluazide (9 ± 2/11 ± 1 mm Hg). Between bisoprolol and bendrofluazide neither in the intention-to-treat nor in the efficacy analysis any difference was found in quality of life variables, such as Health Status Index, somatic symptoms, anxiety, depression, total psychiatric morbidity, cognitive symptoms and hostility score. Compared to baseline the Health Status Index improved (P

With aging, pulse pressure increases. A high pulse pressure has been recognised as an important cardiovascular risk factor. The increase in pulse pressure with aging is mainly due to a decrease in large artery compliance. Compliance and distensibility are large artery wall properties. Compliance is the buffering capacity of the vessel. Distensibility reflects much more the elasticity of the artery. Compliance is related to distensibility and arterial diameter. These large artery wall properties can be measured non-invasively using new echo-tracking techniques. With these techniques it has been shown that the elasticity (distensibility) and the buffering capacity (compliance) of the common carotid artery is decreasing with aging, while diameter of the artery increases. This increase in diameter might be a compensating mechanism to limit the decrease in compliance. There are indications that the effect of aging on large artery wall properties may not be similar at all vascular territories. A decrease in compliance leads to a high pulse pressure and isolated systolic hypertension. The drug of choice for the treatment of isolated systolic hypertension should increase large artery compliance with no, or only minor effect on resistance vessels. This would lead to a decrease in pulse pressure without decreasing mean blood pressure. As a result, systolic but not diastolic blood pressure decreases. It appears that nitrates better than other anti-hypertensive drugs can decrease pulse pressure. They therefore have been advocated for the treatment of isolated systolic hypertension.

Nitrates decrease pulse pressure more than mean arterial pressure (MAP) and are advocated for the treatment of isolated systolic hypertension (ISH). Nitrates show drug tolerance during chronic treatment so an asymmetric dosing regimen may prevent loss of effect of nitrates. This study investigates the anti-hypertensive effect of isosorbide dinitrate (ISDN) given in a twice daily asymmetric dosing regimen in elderly patients with ISH. After a 6-week placebo run-in period, patients entered the double-blind study. Ten patients received placebo and 11 patients ISDN 20 mg b.i.d. for 8 weeks. This dose could be doubled once. Office systolic and diastolic blood pressures (SBP/DBP) and ambulatory BP were measured. Pulse pressure was calculated as SBP-DBP. Office pulse pressure was more reduced during ISDN (17.9%) than with placebo (5%; P < 0.05). SBP and MAP decreased compared to baseline, but the changes were not statistically significant between the two groups. DBP tended to increase with ISDN compared to placebo. Mean 24-h, mean daytime and mean night-time pulse pressure decreased after treatment with ISDN (10.7%, 12.1%, 7.9%, respectively). Pulse pressure tended to decrease more during the day than during the night with ISDN. No changes could be demonstrated with placebo. In conclusion, pulse pressure decreased with ISDN, resulting in a lower SBP without a decrease in DBP. The latter may preserve coronary perfusion in ISH. With the asymmetric dosing regimen the decrease in pulse pressure was not clear at night. Whether a decrease in nocturnal BP, in addition to the spontaneous decrease, is advisable in ISH remains a matter of debate.

Objective: Studies on changes in arterial stiffness and wave reflections during pregnancy are limited to cross-sectional studies. Our aim was to investigate maternal hemodynamic and cardiovascular adaptations at each trimester of pregnancy in a prospective longitudinal case-control study. Methods: Cardiovascular measurements were performed at 12, 20 and 35 weeks of gestation, and included peripheral (Omron M6) and central (Sphygmocor) blood pressures, wave reflection and arterial stiffness measures (Sphygmocor and Esaote AU5 Wall track system). Results: 109 healthy women with a normal pregnancy (mean age 29.3y, range 21–42) and 26 healthy non-pregnant control subjects (mean age 28.4y, range 21–40) were included. Except for peripheral and central systolic blood pressure, all cardiovascular parameters showed significant (p

Objective: Atherosclerotic disease is caused by a combination of systemic, and local factors. The influence of local geometry (affecting local flow conditions) is often neglected. In contrast to the carotid artery, at the iliac-femoral artery region, a large degree of bilateral asymmetry exists. Therefore, our aim was to determine the influence of body side on the prevalence of atherosclerosis (i.e. plaque and intima-media thickening; IMT) at the carotid and femoral arteries. Methods: Data were used from the ASKLEPIOS study, including 2524 apparently healthy subjects with a mean age of 46 year (range 35–55). Echographic images were obtained bilaterally at the common carotid and common femoral arteries. A single observer approach was used for the acquisition and quantification of plaques and IMT. Results: The carotid artery displays almost no left-right difference in IMT values nor plaques. In contrast, the femoral artery displays substantially more atherosclerosis on the right side. Specifically, the IMT distribution at the right common femoral artery is more skewed (Percentile 90 right: 1.11 mm, left 1.01 mm; p