Monitoring compliance in resistant hypertension: an important step in patient management.

Poor compliance with antihypertensive drug regimens is one recognized cause of inadequate blood pressure control. Compliance is difficult to measure, so poor adherence to treatment remains largely undiagnosed in clinical practice. When the therapeutic response to a drug is not the one expected, it is a major challenge for many physicians to decide whether the patient is a non-responder or a non-complier. Poor compliance is therefore often incorrectly interpreted as a lack of response to treatment. Not detecting non-compliance can lead to the wrong measures being taken. Electronic monitoring of compliance provides important longitudinal information about drug-intake behaviour that cannot be obtained in the clinic. Such monitoring can improve both compliance and blood pressure control, and help physicians to make more rational therapeutic decisions. A reliable assessment of compliance could have a great impact on medical costs by preventing unnecessary investigations or dose adaptations in patients who are not taking their drugs adequately, or potentially reducing the number of hospitalizations. Side-effects and lack of effectiveness are two frequent causes of poor compliance. The right choice of antihypertensive drug can therefore contribute to compliance. In this respect, it is important to find a drug regimen that is effective, long-acting and well tolerated. Long-acting antihypertensive drugs that provide good blood pressure control beyond the 24-h dosing period should perhaps be considered as drugs of choice in non-compliant patients with hypertension because they help to prevent the consequences of occasional drug omissions.

Use of non-invasive ambulatory blood pressure monitoring to screen for high-risk hypertensive patients.

Blood pressures measured casually by a doctor often differ considerably from those recorded during everyday activities away from the medical environment. In the present study, we compared office and ambulatory recorded pressures in 475 consecutive untreated patients diagnosed hypertensive by physicians. Blood pressure monitored non-invasively during the day was, on average 15/7 mmHg lower than the corresponding office pressures. The difference between office and ambulatory recorded pressure tended to be greatest in those patients with the highest office blood pressure levels, although the relationship between the two types of measurement was too weak (r = 0.50 and 0.38 for systolic and diastolic pressure, respectively) to have any predictive value in the individual patient. Office blood pressures were at least 10 mmHg higher than ambulatory pressures in 62% of patients for systolic and 42% for diastolic pressure. Blood pressure levels recorded during ambulatory monitoring were higher than in the doctor's office for 18% of patients for systolic and 22% for diastolic pressure. Among patients with systolic pressures of between 161 and 180 mmHg or diastolic pressures between 96 and 105 mmHg when facing a doctor, 27 and 37% respectively, showed markedly lower systolic (less than 140 mmHg) or diastolic (less than 90 mmHg) ambulatory recorded pressures. These data therefore indicate that ambulatory blood pressure monitoring may help to identify those truly hypertensive patients who are most likely to benefit from antihypertensive therapy.

Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells.

Immunotherapy of melanoma is aimed to mobilize cytolytic CD8+ T cells playing a central role in protective immunity. Despite numerous clinical vaccine trials, only few patients exhibited strong antigen-specific T-cell activation, stressing the need to improve vaccine strategies. For a rational development, we propose to focus on molecularly defined vaccine components, and evaluate their immunogenicity with highly reproducible and standardized methods for ex vivo immune monitoring. Careful immunogenicity comparison of vaccine formulations in phase I/II studies allow to select optimized vaccines for subsequent clinical efficacy testing in large scale phase III trials.

'Doctor, what would you do in my position?' Health professionals and the decision-making process in pregnancy monitoring.

OBJECTIVE: Routine prenatal screening for Down syndrome challenges professional non-directiveness and patient autonomy in daily clinical practices. This paper aims to describe how professionals negotiate their role when a pregnant woman asks them to become involved in the decision-making process implied by screening. METHODS: Forty-one semi-structured interviews were conducted with gynaecologists-obstetricians (n=26) and midwives (n=15) in a large Swiss city. RESULTS: Three professional profiles were constructed along a continuum that defines the relative distance or proximity towards patients' demands for professional involvement in the decision-making process. The first profile insists on enforcing patient responsibility, wherein the healthcare provider avoids any form of professional participation. A second profile defends the idea of a shared decision making between patients and professionals. The third highlights the intervening factors that justify professionals' involvement in decisions. CONCLUSIONS: These results illustrate various applications of the principle of autonomy and highlight the complexity of the doctor-patient relationship amidst medical decisions today.

Quantification of 4 antidepressants and a metabolite by LC-MS for therapeutic drug monitoring.

A liquid chromatography method coupled to mass spectrometry was developed for the quantification of bupropion, its metabolite hydroxy-bupropion, moclobemide, reboxetine and trazodone in human plasma. The validation of the analytical procedure was assessed according to Société Française des Sciences et Techniques Pharmaceutiques and the latest Food and Drug Administration guidelines. The sample preparation was performed with 0.5mL of plasma extracted on a cation-exchange solid phase 96-well plate. The separation was achieved in 14min on a C18 XBridge column (2.1mm×100mm, 3.5μm) using a 50mM ammonium acetate pH 9/acetonitrile mobile phase in gradient mode. The compounds of interest were analysed in the single ion monitoring mode on a single quadrupole mass spectrometer working in positive electrospray ionisation mode. Two ions were selected per molecule to increase the number of identification points and to avoid as much as possible any false positives. Since selectivity is always a critical point for routine therapeutic drug monitoring, more than sixty common comedications for the psychiatric population were tested. For each analyte, the analytical procedure was validated to cover the common range of concentrations measured in plasma samples: 1-400ng/mL for reboxetine and bupropion, 2-2000ng/mL for hydroxy-bupropion, moclobemide, and trazodone. For all investigated compounds, reliable performance in terms of accuracy, precision, trueness, recovery, selectivity and stability was obtained. One year after its implementation in a routine process, this method demonstrated a high robustness with accurate values over the wide concentration range commonly observed among a psychiatric population.

A combined ear sensor for pulse oximetry and carbon dioxide tension monitoring: accuracy in critically ill children.

IMPLICATIONS: A new combined ear sensor was tested for accuracy in 20 critically ill children. It provides noninvasive and continuous monitoring of arterial oxygen saturation, arterial carbon dioxide tension, and pulse rate. The sensor proved to be clinically accurate in the tested range.

Quantification of typical antipsychotics in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

A selective and sensitive method was developed for the simultaneous quantification of seven typical antipsychotic drugs (cis-chlorprothixene, flupentixol, haloperidol, levomepromazine, pipamperone, promazine and zuclopenthixol) in human plasma. Ultra-high performance liquid chromatography (UHPLC) was used for complete separation of the compounds in less than 4.5min on an Acquity UPLC BEH C18 column (2.1mm×50mm; 1.7μm), with a gradient elution of ammonium formate buffer pH 4.0 and acetonitrile at a flow rate of 400μl/min. Detection was performed on a tandem quadrupole mass spectrometer (MS/MS) equipped with an electrospray ionization interface. A simple protein precipitation procedure with acetonitrile was used for sample preparation. Thanks to the use of stable isotope-labeled internal standards for all analytes, internal standard-normalized matrix effects were in the range of 92-108%. The method was fully validated to cover large concentration ranges of 0.2-90ng/ml for haloperidol, 0.5-90ng/ml for flupentixol, 1-450ng/ml for levomepromazine, promazine and zuclopenthixol and 2-900ng/ml for cis-chlorprothixene and pipamperone. Trueness (89.1-114.8%), repeatability (1.8-9.9%), intermediate precision (1.9-16.3%) and accuracy profiles (<30%) were in accordance with the latest international recommendations. The method was successfully used in our laboratory for routine quantification of more than 500 patient plasma samples for therapeutic drug monitoring. To the best of our knowledge, this is the first UHPLC-MS/MS method for the quantification of the studied drugs with a sample preparation based on protein precipitation.

Blood pressure monitoring through pharmacies and team-based care of hypertension.

In the last issue of Blood Pressure Monitoring, (James K, Dolan E, O'Brien E. Making ambulatory blood pressure monitoring accessible in pharmacies. Blood Press Monit 2014;19:134-139) elegantly reported for the first time the characteristics of patients attending pharmacies for ambulatory blood pressure measurement (ABPM) and showed that they were similar to those undergoing ABPM through primary care practices. The authors concluded that pharmacies could be a valuable resource to perform ABPM. In the continuity of this study, we would like to emphasize the results of recent studies as well as recommenda-tions of pharmacist involvement in the management of hypertension, more specifically in a team approach.

Monitoring multiple angiogenesis-related molecules in the blood of cancer patients shows a correlation between VEGF-A and MMP-9 levels before treatment and divergent changes after surgical vs. conservative therapy.

Anti-angiogenic therapies are currently in cancer clinical trials, but to date there are no established tests for evaluating the angiogenic status of a patient. We measured 11 circulating angiogenesis-associated molecules in cancer patients before and after local treatment. The purpose of our study was to screen for possible relationships among the different molecules and between individual molecules and tumor burden. We measured VEGF-A, PlGF, SCF, MMP-9, EDB+ -fibronectin, sVEGFR-2, sVEGFR-1, salphaVbeta3, sTie-2, IL-8 and CRP in the blood of 22 healthy volunteers, 17 early breast, 17 early colorectal, and 8 advanced sarcoma/melanoma cancer patients. Breast cancer patients had elevated levels of VEGF-A and sTie-2, colorectal cancer patients of VEGF-A, MMP-9, sTie-2, IL-8 and CRP, and melanoma/sarcoma patients of sVEGFR-1. salphaVbeta3 was decreased in colorectal cancer patients. A correlation between VEGF-A and MMP-9 was found. After tumor removal, MMP-9 and salphaVbeta3 significantly decreased in breast and CRP in colorectal cancer, whereas sVEGFR-1 increased in colorectal cancer patients. In sarcoma/melanoma patients treated regionally with TNF and chemotherapy we observed a rise in VEGF-A, SCF, VEGFR-2, MMP-9, Tie-2 and CRP, a correlation between CRP and IL-8, and a decreased in sVEGFR-1 levels. In conclusion, among all factors measured, only VEGF-A and MMP-9 consistently correlated to each other, elevated CRP levels were associated with tumor burden, whereas sVEGF-R1 increased after tumor removal in colorectal cancer. Treatment with chemotherapy and TNF induced changes consistent with an angiogenic switch. These results warrant a prospective study to compare the effect of surgical tumor removal vs. chemotherapy on some of these markers and to evaluate their prognostic/predictive value.

Monitoring of illicit pill distribution networks using an image collection exploration framework

This paper proposes a novel approach for the analysis of illicit tablets based on their visual characteristics. In particular, the paper concentrates on the problem of ecstasy pill seizure profiling and monitoring. The presented method extracts the visual information from pill images and builds a representation of it, i.e. it builds a pill profile based on the pill visual appearance. Different visual features are used to build different image similarity measures, which are the basis for a pill monitoring strategy based on both discriminative and clustering models. The discriminative model permits to infer whether two pills come from the same seizure, while the clustering models groups of pills that share similar visual characteristics. The resulting clustering structure allows to perform a visual identification of the relationships between different seizures. The proposed approach was evaluated using a data set of 621 Ecstasy pill pictures. The results demonstrate that this is a feasible and cost effective method for performing pill profiling and monitoring.

Non-invasive monitoring of diaphragmatic timing by means of surface contact sensors: an experimental study in dogs

Background: Non-invasive monitoring of respiratory muscle function is an area of increasing research interest, resulting in the appearance of new monitoring devices, one of these being piezoelectric contact sensors. The present study was designed to test whether the use of piezoelectric contact (non-invasive) sensors could be useful in respiratory monitoring, in particular in measuring the timing of diaphragmatic contraction.Methods: Experiments were performed in an animal model: three pentobarbital anesthetized mongrel dogs. The motion of the thoracic cage was acquired by means of a piezoelectric contact sensor placed on the costal wall. This signal is compared with direct measurements of the diaphragmatic muscle length, made by sonomicrometry. Furthermore, to assess the diaphragmatic function other respiratory signals were acquired: respiratory airflow and transdiaphragmatic pressure. Diaphragm contraction time was estimated with these four signals. Using diaphragm length signal as reference, contraction times estimated with the other three signals were compared with the contraction time estimated with diaphragm length signal.Results: The contraction time estimated with the TM signal tends to give a reading 0.06 seconds lower than the measure made with the DL signal (-0.21 and 0.00 for FL and DP signals, respectively), with a standard deviation of 0.05 seconds (0.08 and 0.06 for FL and DP signals, respectively). Correlation coefficients indicated a close link between time contraction estimated with TM signal and contraction time estimated with DL signal (a Pearson correlation coefficient of 0.98, a reliability coefficient of 0.95, a slope of 1.01 and a Spearman's rank-order coefficient of 0.98). In general, correlation coefficients and mean and standard deviation of the difference were better in the inspiratory load respiratory test than in spontaneous ventilation tests.Conclusion: The technique presented in this work provides a non-invasive method to assess the timing of diaphragmatic contraction in canines, using a piezoelectric contact sensor placed on the costal wall.

Status of eye lens radiation dose monitoring in European hospitals.

A questionnaire was developed by the members of WG12 of EURADOS in order to establish an overview of the current status of eye lens radiation dose monitoring in hospitals. The questionnaire was sent to medical physicists and radiation protection officers in hospitals across Europe. Specific topics were addressed in the questionnaire such as: knowledge of the proposed eye lens dose limit; monitoring and dosimetry issues; training and radiation protection measures. The results of the survey highlighted that the new eye lens dose limit can be exceeded in interventional radiology procedures and that eye lens protection is crucial. Personnel should be properly trained in how to use protective equipment in order to keep eye lens doses as low as reasonably achievable. Finally, the results also highlighted the need to improve the design of eye dosemeters in order to ensure satisfactory use by workers.

Propranolol in infantile haemangioma: simplifying pretreatment monitoring.

BACKGROUND: Infantile haemangiomas (IHs) are very common vascular tumours. Propranolol is at present the first-line treatment for problematic and complicated haemangioma. In accordance with a Swiss protocol, children are monitored for 2 days at the start of the treatment to detect possible side effects of this drug. Our study advocates a simplification of the pretreatment monitoring process. METHODS: All children with a problematic and complicated haemangioma treated with propranolol between September 2009 and September 2012 were included in the study. All patients were hospitalised under constant nurse supervision for 48 hours at the start of the treatment and subjected to cardiac and blood measurements. The dosage of propranolol was 1 mg/kg/day on the first day and 2 mg/kg/day from the second day. Demographic data, clinical features, treatment outcome and complications were analysed. RESULTS: Twenty-nine infants were included in our study. Of these, 86.2% responded immediately to the treatment. There were no severe adverse reactions. Six patients presented transient side effects such as bradycardia, hypotension after the first dose and hypoglycaemia later. No side effects occurred after the second dose. Treatment was never interrupted. CONCLUSION: Propranolol (a β-blocker) is a safe treatment for problematic IH. Side effects may occur after the first dose. A strict 48 hour monitoring in hospital is expensive and may be unnecessary as long as the contraindications for the drug are respected.