Blood pressure in the Congolese adult population of South Kivu, Democratic Republic of Congo: Preliminary results from the Bukavu Observ Cohort Study.

BACKGROUND: 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. METHODS: 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. RESULTS: The average age of the entire group was 33.0±16.7 years. Compared to men, women had significantly higher obesity indices (P<0.0001), lower blood pressure between 20 and 39 years of age (P<0.0001) but higher blood pressure at 60 years of age and older (P<0.0001). 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. CONCLUSIONS: 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.

Sunitinib for metastatic renal cell cancer patients: observational study highlighting the risk of important drug-drug interactions.

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.

[Effectiveness of pharmaceutical care for patients with COPD: translated review of the recently published PHARMACOP trial]. / Efficacité des soins pharmaceutiques auprès de patients atteints de BPCO: compte-rendu de l'etude PHARMACOP récemment publiée.

BACKGROUND AND AIM: Few well-designed randomized controlled trials (RCT) regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with Chronic Obstructive Pulmonary Disease [COPD) have been conducted. We assessed the effectiveness of a pharmaceutical care program for patients with COPD. METHODS: The PHARMACOP-trial was a single-blind 3-month RCT, conducted in 170 community pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged > or = 50 years, and with a smoking history > or = 10 pack-years. A computer-generated randomization sequence allocated patients to intervention (n = 371), receiving protocol-defined pharmacist care, or control group (n = 363), receiving usual pharmacist care 11:1 ratio, stratified by center). Interventions, focusing on inhalation technique and adherence to maintenance therapy, were carried out at start of the trial and at one month follow-up. Primary outcomes were inhalation technique and medication adherence. Secondary outcomes were exacerbation rate, dyspnea, COPD specific and generic health status and smoking behavior. RESULTS: From December 2010 to April 2011, 734 patients were enrolled. 42 patients (5.7%) were lost to follow-up. At the end of the trial, inhalation score (Mean estimated difference [delta], 13.5%; 95% Confidence Interval [CI], 10.8-16.1; P < .0001] and medication adherence [(delta, 8.51%; 95% CI, 4.63-12.4; P < .0001) were significantly higher in the intervention group compared to the control group. In the intervention group, a significantly lower hospitalization rate was observed (9 vs 35 hospitalizations; Rate Ratio, 0.28; 95% CI, 0.12-0.64; P = .003). No other significant between-group differences were observed. CONCLUSION: The PHARMACOP-trial demonstrates that pragmatic pharmacist care programs improve both inhalation technique and medication adherence in patients with COPD and could reduce hospitalization rates. The protocolled intervention used in this trial was specifically designed for and evaluated in (Belgian) community pharmacies. This may facilitate future implementation in the Belgian context.

The effects of abrupt antipsychotic discontinuation in cognitively impaired older persons: a pilot study.

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 (n = 40) had a mean age of 84 years (range 67-95) 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, p = 0.003). 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 (p = 0.345). 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.

Self-medication of regular headache: a community pharmacy-based survey.

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.

[Self-medication of regular headache: a community pharmacy-based survey in Belgium]. / Automédication des céphalées fréquentes: étude dans les officines belges.

AIM: 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 ii) a questionnaire to assess current headache medication and previous physician diagnosis, (ii) the ID Migraine Screener [ID-M] and (iii) the MIDAS questionnaire. RESULTS: Forty-four % 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=51). 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 among subjects seeking self-medication for regular headache. Community pharmacists have a strategic position in education and referral of these self-medicating headache patients.

Geographical variation of COVID-19 vaccination coverage, ethnic diversity and population composition in Flanders.

The vaccination coverage in Flanders is high, but some regions show lower vaccination willingness as compared to the overall vaccination coverage. Beginning November of 2021, the vaccination rate in Flanders was above 93% in age groups above 45 years, and around 85% in the age groups 12 to 44 years. Apart from Flanders as a whole, focus here is on the health sector Maasland, which has a slightly lower vaccination rate, especially in the age groups 12 to 44 years. In the Maasland region, located on the eastern border of Flanders, there are between 1% and 10% less vaccinated individuals than expected according to the vaccination rate in the whole of Flanders, with lowest vaccination rates in the south of the Maasland region. We study the impact of ethnic diversity in the population, population composition with respect to the ethnicity of individuals (in the sense of how the local population composition differs from the Flemish average), and socio-economic status on the vaccination rate at the level of the statistical sector, apart from the effect of age. We explain the statistical methods to investigate geographical differences and illustrate how one can deal with incomplete information in vaccination registries. Ethnic diversity in a region is associated with lower vaccination rates, as is a lower regional socio-economic status. The composition of the population in Maasland is associated with a 35% reduction in the odds to get vaccinated as compared to the overall Flemish population.

Effectiveness of a community pharmacist intervention in diabetes care: a randomized controlled trial.

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.

Efficacy, tolerability and safety of nebivolol in patients with hypertension and diabetes: a post-marketing surveillance study.

BACKGROUND AND OBJECTIVES: Hypertension is a widely prevalent condition of elevated blood pressure (BP) and is the leading risk factor for the development of cardiovascular disease (CVD). Many patients have additional risk factors such as diabetes mellitus (DM) or previous history of CVD. Nebivolol is a third-generation beta (beta)-blockers which has been shown not to influence metabolic parameters in patients with DM. This postmarketing surveillance study aimed to collect information on the efficacy, safety and tolerability of nebivolol in hypertensive patients with concomitant DM. PATIENTS AND METHODS: Hypertensive patients with DM followed by 52 cardiologists, internal medicine specialists and general practitioners, between 24 August 2003 and 9 January 2007 in The Netherlands were included in this study. Physicians were asked to survey nebivolol treatment for 6 months. RESULTS: A total of 510 patients were enrolled. Overall, 93.3% of patients were diagnosed with essential hypertension and 6.7% with secondary hypertension. All patients were co-diagnosed with DM. Nebivolol therapy was associated with a significant reduction in both systolic blood pressure (BP) and diastolic BP versus baseline (p < 0.001 for both). These reductions were seen regardless of reason for initiation of nebivolol (i.e. first diagnosis of hypertension, resistance or intolerance to previous antihypertensive medication, or other reasons). A significant improvement in blood glucose was seen at 4 months (-0.6 mmol/L; p = 0.021). Significant reductions in total cholesterol (-1.45 mmol/L; p = 0.006), low density lipoprotein (LDL) cholesterol (-1.32 mmol/L; p = 0.003) and LDL/high density lipoprotein (HDL) cholesterol ratio (-0.77; p = 0.011) were observed at 2 months. No significant changes were seen in HDL cholesterol and triglycerides. CONCLUSION: Nebivolol treatment was associated with a significantly reduced BP, improved blood glucose and LDL cholesterol levels and was well tolerated in hypertensive patients with concomitant DM.

[Management of COPD in community pharmacy]. / Traitement de la BPCO: quel est le rôle du pharmacien d'officine?

BACKGROUND: This observational study aimed to provide a detailed description of (i) drug therapy, (ii) drug adherence, (iii) inhalation technique, and (iv) health status of COPD patients recruited via community pharmacies. Based on these results, problem areas can be detected and targeted pharmacist interventions for improvement of COPD management could be developed. METHOD: We conducted a cross-sectional, observational study in 93 pharmacies (Belgium). Participants (n = 555) completed a questionnaire collecting personal characteristics, smoking history, influenza vaccination, COPD medication and side effects. Adherence to COPD maintenance medication was analysed 1 year-retrospectively through prescription refill rates. Inhalation technique was scored using a checklist. RESULTS: The COPD patients had a mean age of 68.6 yr, 73.7% were men and 37.2% were current smokers. The influenza vaccination status was significantly lower in patients aged < 65 yr (65.7%) than in patients aged > or = 65 years (86.2%) (p < 0.001). Fixed combinations of inhaled corticosteroids and long-acting beta2-agonists were the most frequently used COPD medications (75.4%). About 48% of patients was underadherent (< 80% adherence), 47% was adherent (80-120% adherence) and 5% was overadherent (> 120% adherence). Twenty-one % of patients made major inhalation technique errors with rescue medication; these were all errors in handling pressurized metered dose inhalers (pMDI's). CONCLUSION: This study on COPD management in primary care highlights 4 main aspects which could be improved: (i) drug adherence, (ii) inhalation technique with pMDI's, (iii) influenza vaccination in COPD patients < yr and (iv) smoking cessation.

Symposium "Clinical Pharmacology Anno 2008". 10th Heymans Memorial Lecture.

Genetic factors have been suggested depending on the drug, to account for 20 to 95 % of the variability in drug disposition and effects. Pharmacogenetics is defined as the study of interindividual variations in DNA sequence related to drug disposition or drug action that can influence clinical response. In contrast, pharmacogenomics is defined more broadly as the application of genomics to elucidate disease susceptibility, drug discovery, pharmacological function, drug disposition and therapeutic response. The best recognized examples of genetic polymorphisms that influence drug response in humans are highly penetrant monogenic traits of drug metabolizing enzymes (DME). Inherited difference in a single gene of DME has such a profound effect on the pharmacokinetics of a drug resulting in more than a 100 fold difference in systemic drug exposure with clinically important effect on drug response. Loss of function or gene duplication of DME genes have been identified as mechanisms of severe and life-threatening toxicity and poor treatment response, respectively. There is a growing list of genetic polymorphisms in drug transporters and targets that have been shown to influence drug response. However, drug response involves many genes and therefore new strategies are needed to identify, for a given drug, the relevant genes and genetic polymorphisms and the pathways and processes in their interaction. These new strategies include genome-wide haplotype mapping, gene expression analyses, proteomic methods. In addition nongenetic factors will modify drug response. A major limitation in implementing pharmacogenetic testing in the clinical setting is the lack of clinical trials demonstrating that such testing can improve drug therapy by reducing toxicity and increasing efficacy.

The paradox of scored tablets: a cost-saving risk.

One of the cornerstones of pharmacotherapy is the proper dose of medicine, which should ideally be tailored to the individual patient. However, even if clinically possible, this is economically not feasible as a too large number of different dosage strengths would be required. Therefore, a balance is required between the patient's benefit/risk and the cost to the individual and society on the other hand. Scored or splitted tablets were, and still are, often used strategies to these opposite interests, enabling more dose-flexibility, but also at the same time increasing the dose-variability as a consequence of the breaking process. The question of how to deal with this paradox was investigated by exploring the prevalence and classification of scored tablets as well as the cost-benefits. A strategy for clinical pharmacologists is presented to improve the outcome of this paradox.

[The good use of home blood pressure monitoring. Consensus document]. / Document de consensus. Du bon usage de l'automesure tensionnelle.

Self or home blood pressure measurement (HBPM) is increasingly popular. Its prognostic value and clinical interest in the diagnosis and follow-up of hypertension are well established. In addition, experts widely agree on the fact that it improves hypertension management and therapeutic compliance. In particular, HBPM often allows to detect white coat hypertension (to be confirmed by 24-hour ambulatory blood pressure measurement). Unfortunately, a large part of HBPM devices in the European Union have not fulfilled independent validation criteria. Furthermore, many patients buy and use such devices without medical supervision. This consensus document summarizes the advantages and disadvantages of HBPM and the conditions of a proper use, in agreement with the recent European and American guidelines.

Effectiveness of pharmacist intervention for asthma control improvement.

Education on optimal medication use is an essential strategy to improve asthma control. The current authors investigated whether pharmacist interventions, focused on appropriate use of asthma medication and tailor-made to the patient's current asthma control, would improve asthma control in adult patients. A 6-month randomised, controlled, parallel-group trial was conducted in 66 community pharmacies in Belgium. Patients were randomly assigned to receive usual pharmacist care (n = 94) or a pre-defined pharmacist intervention (n = 107). This intervention mainly focused on improving inhalation technique and medication adherence. Primary outcome was the level of asthma control, as assessed by the Asthma Control Test (ACT). Mean ACT scores did not change from baseline for both study groups. However, a pre-defined subgroup analysis of patients having insufficiently controlled asthma at baseline showed that the intervention had significantly increased the ACT score after 6 months compared with usual care. The intervention also reduced, for the complete study group, reliever medication use and the frequency of night-time awakenings due to asthma. Inhalation technique and adherence to controller medication were significantly better in the intervention group. In conclusion, pragmatic community pharmacy-based programmes can significantly improve therapeutic outcomes in adult asthma patients.

Arterial structure and function and environmental exposure to cadmium.

OBJECTIVES: Few studies have addressed the effect of cadmium toxicity on arterial properties. METHODS: We investigated the possible association of 24 h urinary cadmium excretion (an index of lifetime exposure) with measures of arterial function in a randomly selected population sample (n = 557) from two rural areas with low and high environmental exposure to cadmium. RESULTS: 24 h urinary cadmium excretion was significantly higher in the high compared with the low exposure group (p<0.001). Even though systolic (p = 0.42), diastolic (p = 0.14) and mean arterial pressure (p = 0.68) did not differ between the high and low exposure groups, aortic pulse wave velocity (p = 0.008), brachial pulse pressure (p = 0.026) and femoral pulse pressure (p = 0.008) were significantly lower in the high exposure group. Additionally, femoral distensibility (p<0.001) and compliance (p = 0.001) were significantly higher with high exposure. Across quartiles of 24 h urinary cadmium excretion (adjusted for sex and age), brachial (p for trend = 0.015) and femoral (p for trend = 0.018) pulse pressure significantly decreased and femoral distensibility (p for trend = 0.008) and compliance (p for trend = 0.007) significantly increased with higher cadmium excretion. After full adjustment, the partial regression coefficients confirmed these associations. Pulse wave velocity (beta = -0.79+/-0.27; p = 0.004) and carotid (beta = -4.20+/-1.51; p = 0.006), brachial (beta = -5.43+/-1.41; p = 0.001) and femoral (beta = -4.72+/-1.74; p = 0.007) pulse pressures correlated negatively, whereas femoral compliance (beta = 0.11+/-0.05; p = 0.016) and distensibility (beta = 1.70+/-0.70; p = 0.014) correlated positively with cadmium excretion. CONCLUSION: Increased cadmium body burden is associated with lower aortic pulse wave velocity, lower pulse pressure throughout the arterial system, and higher femoral distensibility.

Naftidrofuryl for intermittent claudication.

BACKGROUND: Lifestyle changes and cardiovascular prevention measures are a primary treatment for intermittent claudication (IC). Symptomatic treatment with vasoactive agents (Anatomic Therapeutic Chemical Classification (ATC) for medicines from the World Health Organisation class CO4A) is controversial. OBJECTIVES: To evaluate evidence on the efficacy and safety of oral naftidrofuryl (ATC CO4 21) versus placebo on the pain-free walking distance (PFWD) of people with IC by using a meta-analysis based on individual patient data (IPD). SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Trials Register (last searched December 2007) and CENTRAL (last searched 2007, Issue 4). We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts, the Science Citation Index and contacted the authors and checked the reference lists of retrieved articles. We asked the manufacturing company for IPD. SELECTION CRITERIA: We included only randomized controlled trials (RCTs) with low or moderate risk of bias for which the IPD were available. DATA COLLECTION AND ANALYSIS: We collected data from the electronic data file or from the case report form and checked the data by a statistical quality control procedure. All randomized patients were analyzed following the intention-to-treat (ITT) principle. The geometric mean of the relative improvement in PFWD was calculated for both treatment groups in all identified studies. The effect of the drug was assessed compared with placebo on final walking distance (WDf) using multilevel and random-effect models and adjusting for baseline walking distance (WD0). For the responder analysis, therapeutic success was defined as an improvement of walking distance of at least 50%. MAIN RESULTS: We included seven studies in the IPD (n = 1266 patients). One of these studies (n = 183) was only used in the sensitivity analysis so that the main analysis included 1083 patients. The ratio of the relative improvement in PFWD (naftidrofuryl compared with placebo) was 1.37 (95% confidence interval (CI) 1.32 to 1.51, P < 0.001). The absolute difference in responder rate, or proportion successfully treated, was 22.3% (95% CI 17.1% to 27.6%). The calculated number needed to treat was 4.5 (95% CI 3.6 to 5.8). AUTHORS' CONCLUSIONS: Naftidrofuryl has a statistically significant and clinically meaningful effect of improving walking distance in the six months after initiation of therapy for people with intermittent claudication. Access by researchers to data from RCTs that is suitable for IPD analysis should be possible through repositories of data from pharmacological trials. Regular formal appraisal of the balance of risk and benefit is needed for older pharmaceutical products.

Determining carotid artery pressure from scaled diameter waveforms: comparison and validation of calibration techniques in 2026 subjects.

Calibrated diameter distension waveforms could provide an alternative for local arterial pressure assessment more widely applicable than applanation tonometry. We compared linearly and exponentially calibrated carotid diameter waveforms to tonometry readings. Local carotid pressures measured by tonometry and diameter waveforms measured by ultrasound were obtained in 2026 subjects participating in the Asklepios study protocol. Diameter waveforms were calibrated using a linear and an exponential calibration scheme and compared to measured tonometry waveforms by examining the mean root-mean-squared error (RMSE), carotid systolic blood pressure (SBPcar) and augmentation index (AIx) of calibrated and measured pressures. Mean RMSE was 5.2(3.3) mmHg (mean(stdev)) for linear and 4.6(3.6) mmHg for exponential calibration. Linear calibration yielded an underestimation of SBPcar by 6.4(4.1) mmHg which was strongly correlated to values of brachial pulse pressure (PPbra) (R = 0.4, P < 0.05). Exponential calibration underestimated true SBPcar by 1.9(3.9) mmHg, independent of PPbra. AIx was overestimated by linear calibration by 1.9(10.1)%, the difference significantly increasing with increasing AIx (R = 0.25, P < 0.001) and by exponential calibration by 5.4(10.6)%, independently of the value of AIx. Properly calibrated diameter waveforms offer a viable alternative for local pressure estimation at the carotid artery. Compared to linear calibration, exponential calibration significantly improves the pressure estimation.

Three- and four-element Windkessel models: assessment of their fitting performance in a large cohort of healthy middle-aged individuals.

Lumped-parameter models are used to estimate the global arterial properties by fitting the model to measured (aortic) pressure and flow. Different model configurations coexist, and it is still an open question as to which model optimally reflects the arterial tree and leads to correct estimates of arterial properties. An assessment was made of the performance of (a) the three-element Windkessel model (WK3) consisting of vascular resistance R, total arterial compliance C, and characteristic impedance Zc; (b) a four-element model with an inertance element L placed in parallel with Zc (WK4-p); and (c) a four-element model with L placed in series with Zc (WK4-s). Models were fitted to data measured non-invasively in 2404 healthy subjects, aged between 35 and 55 years. It was found that model performance segregated into two groups. In a group containing 20 per cent of the dataset (characterized by low blood pressure and wave reflection) the WK4-p model outperformed the other models, with model behaviour as envisioned by its promoters. In these cases, the WK3 and WK4-s models led to increased overestimation of total arterial compliance and underestimation of characteristic impedance. However, in about 80 per cent of the cases, the WK4-p model showed a behaviour that was very similar to that of the WK3 and WK4-s models. Here, the WK4-s model yielded the best quality of fit, although model parameters reached physically impossible values for L in about 12 per cent of all cases. The debate about which lumped-parameter model is the better approximation of the arterial tree is therefore still not fully resolved.

Medication use and disease control of asthmatic patients in Flanders: a cross-sectional community pharmacy study.

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 beta2-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.

Remodeling of the vascular tree in hypertension: drug effects.

The primary aim of current antihypertensive therapy is to lower blood pressure through the reduction of peripheral vascular resistance. Resistance reduction is achieved primarily by interference with acutely acting pressor stimuli. However, recent research has stressed the importance of slow pressor stimuli, which act by gradually remodeling the vascular tree. Long-term remodeling is achieved by a chronic change in vessel number, vascular diameter or wall thickness, involving both physical and chemical factors. The chemical mediators belong to a group of endogenous growth-affecting factors. As Harry Struyker Boudier and colleagues explain in this review, although there are thus far no specific drugs to antagonize the effects of these factors, several therapeutically used antihypertensives influence their action. Moreover, the concept that vascular remodeling is important in hypertension offers exciting new therapeutic targets.