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B Boulanger

Publications and source records attributed to B Boulanger.

At least 19 recordsLinked to original sources
PubMed2006

Robustness testing of a chiral NACE method for R-timolol determination in S-timolol maleate and uncertainty assessment from quantitative data.

A robustness test of a capillary electrophoresis method for the chiral separation of timolol in nonaqueous acidified media was performed. A two-level Plackett-Burman design was applied in which one qualitative and six quantitative factors were examined. Resolution, migration times and relative migration times to pyridoxine (selected as internal standard) were examined as qualitative responses to evaluate electrophoretic performance. A quantitative response, the content of R-timolol in S-timolol maleate sample, was also considered. Even though some significant factor effects were observed on the qualitative responses, it was still possible to quantify the R-timolol in the S-timolol maleate samples properly. The quantitative response was not significantly affected by the selected factors, demonstrating the robustness of the procedure. However, the use of different HDMS-beta-CD batches seemed to affect both types of responses necessitating to introduce a warning in the procedure. Since the experiments of the Plackett-Burman design can be assimilated to laboratories in an interlaboratory study, uncertainty can be evaluated using the robustness test data. The robustness test was set-up in such a way that the required variances could be estimated.

Adrenergic beta-Antagonists↗
PubMed2006

The transfer of a LC-UV method for the determination of fenofibrate and fenofibric acid in Lidoses: use of total error as decision criterion.

Two new statistical approaches to assess the validity of the transfer of a LC-UV method for the determination of fenofibrate and fenofibric acid were investigated and compared to the conventional approaches generally used in this domain. These new approaches, namely the Tolerance Interval and the Risk approaches, are based on the simultaneous evaluation of the systematic (or trueness) and random (or precision) errors of the transfer into a single criterion called total error (or accuracy). The results of the transfer showed that only the total error based approaches fulfilled the objective of an analytical method transfer, i.e. to give guarantees that each future measurement made by the receiving laboratory will be close enough to the true value of the analyte in the sample. Furthermore the Risk approach was the most powerful one and allowed the estimation of the risk to have future measurements out of specification in the receiving laboratory, therefore being a risk management tool.

Chromatography, Liquid↗
PubMed2006

[Harmonisation of validation strategies and estimation of the associated uncertainty in the framework of assay laboratoires accreditation].

In order to achieve the harmonization of validation strategies, the interpretation of several validation criteria is proposed. Furthermore, a simple and visual decision tool to assess the validity of an analytical procedure is described: the accuracy profile based on the estimation of the total error of the measurements. This profile build with beta-expectation tolerance intervals can also compute with efficiency the uncertainty related to the results of a laboratory, which is an essential parameter for the accreditation of laboratories under ISO 17025.

Accreditation↗
PubMed2006

[Comparison of three approaches for uncertainty estimation].

Three different approaches for the estimation of uncertainty measurements using the same analytical method were compared, namely validation, robustness and inter-laboratory studies. The uncertainty obtained with the robustness study! predicted well the uncertainty of the inter-laboratory study. On the other hand, the uncertainty estimation obtained with the validation study is lower than those obtained with the two other approaches but is still acceptable as long as the analytical method will be used in a single laboratory.

Chromatography, Liquid↗
PubMed2004

Experimental demonstration of a pure third-order optical parametric downconversion process.

We report what is, to the best of our knowledge, the first experiment on third-order optical difference frequency generation. The nonlinear medium is a phase-matched KTiOPO4 crystal pumped at 532 and 1665 nm in the picosecond regime. The proposed experimental configuration leads to an efficient and pure cubic process, with generation of 4.5 microJ/pulse at 1474 nm. This result opens the way to new quantum experiments on three-photon Greenberger-Horne-Zeilinger entanglement.

Journal Article↗
PubMed2004

Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal--Part I.

This paper is the first part of a summary report of a new commission of the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP). The main objective of this commission was the harmonization of approaches for the validation of quantitative analytical procedures. Indeed, the principle of the validation of theses procedures is today widely spread in all the domains of activities where measurements are made. Nevertheless, this simple question of acceptability or not of an analytical procedure for a given application, remains incompletely determined in several cases despite the various regulations relating to the good practices (GLP, GMP, ...) and other documents of normative character (ISO, ICH, FDA, ...). There are many official documents describing the criteria of validation to be tested, but they do not propose any experimental protocol and limit themselves most often to the general concepts. For those reasons, two previous SFSTP commissions elaborated validation guides to concretely help the industrial scientists in charge of drug development to apply those regulatory recommendations. If these two first guides widely contributed to the use and progress of analytical validations, they present, nevertheless, weaknesses regarding the conclusions of the performed statistical tests and the decisions to be made with respect to the acceptance limits defined by the use of an analytical procedure. The present paper proposes to review even the bases of the analytical validation for developing harmonized approach, by distinguishing notably the diagnosis rules and the decision rules. This latter rule is based on the use of the accuracy profile, uses the notion of total error and allows to simplify the approach of the validation of an analytical procedure while checking the associated risk to its usage. Thanks to this novel validation approach, it is possible to unambiguously demonstrate the fitness for purpose of a new method as stated in all regulatory documents.

Chemistry Techniques, Analytical↗
PubMed2003

An analysis of the SFSTP guide on validation of chromatographic bioanalytical methods: progress and limitations.

The Société Française des Sciences et Techniques Pharmaceutiques (SFSTP) published in 1997 a guide on the validation of chromatographic bio-analytical methods, which introduces new concepts in three different areas: stages of the validation, test of acceptability of a method and design of experiments to perform. In 'stages of validation', the SFSTP guide requires two phases to validate a method. The first phase, called 'prevalidation', is intended to (1) identify the model to use for the calibration curve; (2) evaluate the limits of quantitation; and (3) provide good estimates of the precision and bias of the method before designing the 'validation' phase per se. In the 'test of acceptability', the use of the interval hypotheses is envisaged by the SFSTP guide, not on the parameters of bias and precision, but on individual results by mixing mean bias and intermediate precision in a single test. The SFSTP guide also avoids the use of Satterthwaite's df for testing the acceptability. The reasons for those choices are discussed extensively. In 'design of experiments', much effort has been devoted to improving the quality of results by optimally designing and sizing the experiments to perform in validation. The rationale for using near D-optimal designs for the calibration curve is demonstrated and sample sizes are proposed to correctly size the validation experiments.

Chromatography↗
PubMed2001

Minimally invasive retrieval of a foreign body after penetrating lung injury.

Minimally invasive techniques are increasingly used in the management of trauma victims. We report the case of a young man in a motor vehicle crash who sustained a penetrating wound to the anterior left chest caused by the automobile stick shift. Subsequent imaging demonstrated a large foreign body in the left lung. The foreign body was removed successfully by videothoracoscopy, and the patient made a full recovery. This case demonstrates the inroads that minimally invasive surgery is making in care of the injured and highlights an excellent technique for dealing with pulmonary foreign bodies.

Accidents, Traffic↗
PubMed2001

Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine.

OBJECTIVE: Non-compliance presents a constant challenge to effective therapy. Many studies only investigate early treatment discontinuation and not other measures like adherence to treatment regimen. We compared adherence in depressed patients using either a selective serotonin reuptake inhibitor (fluoxetine) or a tricyclic antidepressant (amitriptyline), and examined its clinical relevance through adverse events, drop-out rates, and outcome. Adherence was measured electronically with the MEMS (Medication Event Monitoring System). DESIGN: Nine-week double blind, randomized controlled trial. SETTING: Ambulatory psychiatric care. PATIENTS: Random sample of 66 depressed (DSM-III-R criteria) patients. INTERVENTION: Fluoxetine 20 mg or amitriptyline 150 mg. MAIN OUTCOME MEASURES: Time course of adherence and its relation to severe adverse events, drop-outs and outcome. RESULTS: Non-adherence to the treatment regimen occurred frequently in both treatment groups: 31% of patients had at least one 3-day drug holiday, and 34% of patients had at least one episode of three pills in a 24-h period. Over-consumption occurred more frequently during the early phases of treatment while under-consumption occurred more frequently during the later phases. Patients on amitriptyline (P=0.03) and patients with a higher pill intake (P=0.01) experienced more severe adverse events. Patients on amitriptyline (P=0.009) and patients with a lower adherence to the treatment regimen (P=0.004) discontinued from treatment more frequently. The final Hamilton score was significantly predicted by a longer duration of treatment and by a better adherence, but only in amitriptyline users. CONCLUSIONS: Non-adherence to the treatment regimen has important clinical consequences. Pharmacodynamics and human behavior predict risk for severe adverse events and drop-outs. Moreover, in amitriptyline users but not in fluoxetine users, better adherence predicts a better outcome.

Adult↗
PubMed2001

Development and validation of an automated method for the liquid chromatographic determination of sotalol in plasma using dialysis and trace enrichment on a cation-exchange pre-column as on-line sample preparation.

A fully automated method for the determination of sotalol in human plasma was developed, involving dialysis through a cellulose acetate membrane, clean-up and enrichment of the dialysate on a strong cation-exchange pre-column and subsequent liquid chromatographic (LC) analysis with UV detection. All sample handling operations were carried out by means of an ASTED system. Before starting dialysis, the trace enrichment column (TEC) was conditioned. The plasma sample, to which the internal standard (atenolol) was automatically added, was then loaded in the donor channel and was kept static while the dialysis liquid, consisting of 0.017 M acetic acid, was passed through the acceptor channel in successive pulses. After each pulse, the dialysate was dispensed onto the TEC. When dialysis was discontinued, the analytes were eluted from the TEC by the LC mobile phase by rotation of a switching valve and transferred to the analytical column packed with octyl silica. The LC mobile phase was a mixture of methanol and pH 7.0 phosphate buffer containing 1-octanesulfonate at a concentration of 7.5 x 10(-4) M (19:81; v/v). The UV detection was performed at 230 nm. The influence of several parameters of the dialysis and trace enrichment processes on analyte recovery and method selectivity was investigated. The method was then validated. The mean absolute recovery for sotalol was about 60%. The limit of quantitation was 25 ng/ml and R.S.D. for repeatability and intermediate precision obtained at a concentration level of 50 ng/ml were 4.3 and 5.8%, respectively.

Automation↗
PubMed2001

Telemedicine: a solution to the followup of rural trauma patients?

BACKGROUND: Outpatient followup of rural trauma patients is problematic for physicians and patients. Our hypothesis was that telemedicine-based followup of trauma patients discharged to remote areas is feasible and is associated with high patient and physician satisfaction. STUDY DESIGN: We chose 11 counties in Kentucky surrounding a remote telemedicine site as our region of interest. Any adult trauma patient who was discharged from our Level I trauma center to this geographic region was eligible to have routine followup appointment(s) at the TeleTrauma Clinic. Patients were examined and interviewed with the assistance of a nurse, an electronic stethoscope, and a close-up imaging instrument. Radiographs performed at the telemedicine site were viewed. Patients and physicians completed a survey after the appointment. RESULTS: To date, we have conducted 22 telemedicine-based followup assessments of trauma patients. The average age and Injury Severity Score were 42 years and 18, respectively. Plain radiographs were reviewed in 13 cases. Our patient surveys indicated a high degree of satisfaction with the teleappointment. In 15 of 22 patients, no further clinical followup was arranged. The differences in travel distances and times for an appointment at the TeleTrauma Clinic versus an appointment at our Level I trauma center were significant. The average and median duration of the appointments was 14 minutes. All telemedicine encounters were done by two physicians, who recorded a high level of satisfaction. CONCLUSIONS: Our early experience with the outpatient followup of remote trauma victims by telemedicine is encouraging. Patient surveys indicate a high degree of satisfaction. As a result of our favorable experience, telemedicine-based followup may be expanded to other regions of Kentucky.

Adolescent↗
PubMed2001

Compliance with antidepressants in a primary care setting, 1: Beyond lack of efficacy and adverse events.

BACKGROUND: Treatment guidelines recommend antidepressant treatment be continued for at least 6 months to ensure maximal improvement and to prevent relapse. Naturalistic studies show that the average length of treatment is shorter than 6 months and that dropout rates are high. Factors leading patients to discontinuation of therapy are not well understood. This study investigates when and why patients stop treatment and whether they inform their doctors. METHOD: Patients (N = 272) receiving antidepressant therapy due to an episode of major depressive disorder (DSM-IV) were asked to complete an antidepressant compliance questionnaire. Patients were then telephoned monthly while they continued on antidepressant therapy, up to 6 months. During each call, patients were asked standard questions. RESULTS: By endpoint, 53% of patients had discontinued antidepressant treatment. The most common reason given was "feeling better." However, different dropout reasons were prevalent at different times after initiation of therapy. Overall, 24% of the patients did not inform their physician about stopping the antidepressant medication. The likelihood of patients' informing their physicians differed according to the patients' reasons for discontinuation and according to the patients' perceptions of their relationship with their physicians. CONCLUSION: These results provide new guidelines for improving compliance. Strategy should be adapted to the stage of treatment, as patients' reasons for discontinuation vary as treatment progresses. The attitude of the physician and the information provided by the physician significantly influence whether patients inform the physician when they discontinue antidepressant therapy.

Adult↗
PubMed2001

Compliance with antidepressants in a primary care setting, 2: the influence of gender and type of impairment.

BACKGROUND: DSM-IV diagnosis of major depressive disorder includes a requirement that symptoms result in significant clinical distress or impairment. This criterion is difficult to assess and is often overlooked. This study examines the use of the Sheehan Disability Scale as a possible method of assessing impairment, as well as the relationship between functioning and discontinuation of antidepressant medication. METHOD: Patients (N = 272) receiving antidepressant therapy due to an episode of major depressive disorder were asked to complete an antidepressant compliance questionnaire. Patients were telephoned monthly while they continued on antidepressant therapy, up to 6 months. During each call, the Sheehan Disability Scale was administered. RESULTS: Of patients referred to this study, 94.8% met DSM-IV criteria of at least 5 symptoms of major depressive disorder. Most patients had initial scores ranging from 5 to 8 on all 3 Sheehan disability subscales (occupational, social, and family functioning); 72% of patients had at least moderate impairment (scores > or = 4) on all 3 subscales. After 8 weeks of treatment, 42% of patients had scores < 4 on all 3 subscales (recovery); after 24 weeks, 64% of patients had scores < 4 on all 3 subscales. Dropout risk in men was related to improvement in occupational, social, and family functioning, whereas dropout risk in women was related only to improvement in family functioning. CONCLUSION: The Sheehan Disability Scale can be valuable in assessing impairment and thus in correctly diagnosing major depressive disorder. We suggest that scores of 4 or more (moderate impairment) on all 3 subscales indicate sufficient impairment for a strict diagnosis of major depressive disorder. Functional symptoms continued to improve for up to 24 weeks on antidepressant therapy, suggesting 6 months or more of therapy is necessary for maximum functional improvement. Premature discontinuation of antidepressant therapy is more likely to occur in women who experience significant improvement in family functioning or men who experience significant improvement in any functional area.

Adult↗
PubMed2000

Relationship between pericardial pressure and lymphatic pericardial fluid transport in sheep.

We investigated the relationship between pericardial pressure and the volumetric lymphatic clearance rate of pericardial fluid in sheep. A single catheter perfusion system was established to deliver tracer to the pericardial cavity and control pericardial pressure. In addition, catheters were placed into the thoracic duct and into the jugular vein at the base of the neck. (125)I-human serum albumin (HSA) was administered into the pericardial perfusate to serve as the lymph flow marker and its concentration monitored in the effluent from the outflow end of the perfusion system. (131)I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, estimates of total pericardial clearance into lymphatics increased significantly as pericardial pressures were elevated in 2. 5 cm H(2)O increments from 2.5 to 12.5 cm H(2)O (P = 0.018). Pericardial lymph transport ranged from 0.89 +/- 0.10 to 3.09 +/- 0. 66 ml/h at 2.5 and 12.5 cm H(2)O pericardial pressure, respectively. The majority of transport occurred through mediastinal vessels with a small proportion (10.3 to 23.9%) being cleared into lymphatics leading to the thoracic duct. We conclude that lymphatic pericardial fluid transport increases approximately 3.5-fold over a pericardial pressure range that encompasses the transition between the shallow and steep portions of the pericardial pressure-volume relationship.

Animals↗
PubMed1999

Pericardial fluid absorption into lymphatic vessels in sheep.

We estimated the volumetric lymphatic clearance rate of pericardial fluid in sheep. In the first group of studies, 125I-human serum albumin (HSA) was injected into the pericardial cavity and after 4 h, various lymph nodes and tissues were excised and counted for radioactivity. Several lymphatic drainage pathways existed defined by elevated 125I-HSA in the middle and caudal mediastinal, intercostal, and the cardiac nodes located near the root of the aorta. In a second group of experiments, the plasma recovery of intrapericardially administered tracer was compared in sheep with intact lymphatics and in animals in which thoracic duct lymph was diverted and other relevant lymphatics ligated. The 4-h plasma recoveries were reduced significantly from an average of 12.2 +/- 3. 4% injected dose in the lymph-intact group to 3.0 +/- 1.1% injected dose in the diverted/ligated group (an inhibition of approximately 75%). In order to estimate the volumetric clearance of pericardial fluid through lymphatics in conscious sheep, 125I-HSA was administered into the pericardial cavity to serve as the lymph flow marker. 131I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, total pericardial clearance into lymphatics averaged 1.50 +/- 0.43 ml/h or approximately 1.13 ml/h if one was to assume that the average 25% recovered plasma tracer in lymph diverted/ligated animals was due to nonlymphatic transport. In conclusion, mediastinal lymphatic pathways remove a volume equivalent to the pericardial volume (8.1 +/- 1.1 ml) every 5.4 to 7. 2 h.

Absorption↗
PubMed1999

Construction of an optimal destructive sampling design for noncompartmental AUC estimation.

Based on toxicokinetic studies of a destructive sampling design, this work was aimed at selecting the number of time points, their locations, and the number of replicates per time point in order to obtain the most accurate and precise noncompartmental estimate of the area under the concentration-time curve (AUC). From a prior population pharmacokinetic model, the design is selected to minimize the scaled mean squared error of AUC. Designs are found for various sample sizes, number of time points, and a distribution of animals across time points from being very unbalanced to balanced. Their efficiencies are compared both theoretically and based on simulations. An algorithm has been implemented for this purpose using the symbolic resolution and numerical minimization capabilities of Mathematica and an example of its use is provided. This method provides efficient tools for constructing, validating, and comparing optimal sampling designs for destructive sampled toxicokinetic studies.

Algorithms↗
PubMed1998

Simultaneous determination of methylphenobarbital enantiomers and phenobarbital in human plasma by on-line coupling of an achiral precolumn to a chiral liquid chromatographic column.

A fully automated liquid chromatographic (LC) method for the simultaneous determination of methylphenobarbital enantiomers and phenobarbital in human plasma has been developed. The method is based on the use of a precolumn packed with an internal-surface reversed-phase packing material (LiChrospher ADS) for sample clean-up coupled to LC analysis on a cellulose tris(4-methylbenzoate) based chiral stationary phase (Chiralcel OJ-R). A 100-microliter plasma sample was injected directly on the precolumn packed with LiChrospher RP-18 ADS using a mixture of pH 5.0 phosphate buffer-methanol (97:3, v/v) as washing liquid. The analytes were then eluted in the back-flush mode with the LC mobile phase. The enantiomeric separation of methylphenobarbital was achieved on Chiralcel OJ-R). The retention times were modelled using a D-optimal design with ten experimental points in order to optimise the LC mobile phase for the separation of phenobarbital from the enantiomers of mephobarbital. The factors selected were the acetonitrile content, the pH and the sodium perchlorate concentration in the mobile phase. A Derringer's desirability function was used to find an optimal and robust solution within the experimental domain. The mobile phase selected consisted of a mixture of pH 7.0 phosphate buffer-acetonitrile (60:40, v/v). The elution profiles of phenobarbital, methylphenobarbital and blank plasma samples on the precolumn and the time needed for analyte transfer from the precolumn to the analytical column were then determined. Finally, the method developed was validated.

Chromatography, Liquid↗