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Biomedical subjects

Nicholas Moore

Publications and source records attributed to Nicholas Moore.

At least 37 records · Page 2Linked to original sources
PubMed2005

Prescription channeling of COX-2 inhibitors and traditional nonselective nonsteroidal anti-inflammatory drugs: a population-based case-control study.

This pharmacoepidemiologic study was conducted to determine whether risk factors for upper gastrointestinal bleeding influenced the prescription of cyclo-oxygenase (COX)-2 inhibitors and traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) at the time when COX-2 inhibitors were first included in the formulary of reimbursed medications. A population-based case-control study was conducted in which the prevalence of risk factors and the medical histories of patients prescribed COX-2 inhibitors and traditional nonselective NSAIDs were compared. The study population consisted of a random sample of members of the Quebec drug plan (age 18 years or older) who received at least one dispensation of celecoxib (n = 42,422; cases), rofecoxib (n = 25,674; cases), or traditional nonselective NSAIDs (n = 12,418; controls) during the year 2000. All study data were obtained from the Quebec health care databases. Adjusting for income level, Chronic Disease Score, prior use of low-dose acetylsalicylic acid, acetaminophen, antidepressants, benzodiazepines, prescriber specialty, and time period, the following factors were significantly associated with the prescription of COX-2 inhibitors: age 75 years or older (odds ratio [OR] 4.22, 95% confidence interval [CI] 3.95-4.51), age 55-74 years (OR 3.23, 95% CI 3.06-3.40), female sex (OR 1.52, 95% CI 1.45-1.58), prior diagnosis of gastropathy (OR 1.21, 95% CI 1.08-1.36) and prior dispensation of gastroprotective agents (OR 1.57, 95% CI 1.47-1.67). Patients who received a traditional nonselective NSAID recently were more likely to switch to a coxib, especially first-time users (OR 2.17, 95% CI 1.93-2.43). Associations were significantly greater for celecoxib than rofecoxib for age, chronic NSAID use, and last NSAID use between 1 and 3 months before the index date. At the time of introduction of COX-2 inhibitors into the formulary, prescription channeling could confound risk comparisons across products.

Adolescent↗
PubMed2005

Simplified ultraviolet liquid chromatographic method for determination of sertindole, dehydrosertindole and norsertindole, in human plasma.

An ultra-violet high-performance liquid chromatographic method was developed for the determination of sertindole, an atypical antipsychotic drug and its main metabolites dehydrosertindole and norsertindole, in human plasma. With a small sample volume, after a single-step liquid-liquid extraction, the compounds were separated on a reversed-phase XTerra RP(18) column, eluted with 45% of acetonitrile and 55% of ammonium acetate buffer (0.05 M, adjusted pH 8) and detected at 256 nm within 11 min. This method shows a good linearity for plasma concentration between 5-100 ng/ml and 100-1000 ng/ml, a good precision (inter and intra day CV < 11%) and a good inter-assay accuracy (bias < 11%). The limit of quantification concentration was 5 ng/ml. The absolute recovery of sertindole was higher than 99%. This rapid and sensitive method could be used for therapeutic drug monitoring as well as for overdose management.

Antipsychotic Agents↗
PubMed2005

A large simple clinical trial prototype for assessment of OTC drug effects using patient-reported data.

PURPOSE: Innovative methods are needed to assess risks related to treatment for common medical conditions, where therapy is usually patient-directed or over-the-counter (OTC), and where tolerability, i.e. patient experienced events, may affect patterns of use. A large-scale, blinded, randomised trial was conducted to compare the tolerability of paracetamol (acetaminophen), aspirin and ibuprofen at OTC doses, with patient-reported adverse event (AE) data as the primary outcome. METHODS: Patients with mild to moderate pain were randomised to either: paracetamol up to 3 g/d, aspirin up to 3 g/d or ibuprofen up to 1200 mg/d for 7 days. Patients recorded AE and severity in a diary as the primary data source. After inclusion, contact with patients by general practitioner (GP) investigators was by telephone after 24 hours and 7-9 days, and unscheduled visits, when GPs recorded AE. The study outcome was the frequency of significant adverse event (SGAE) (serious, severe, moderate or undefined intensity, or resulting in withdrawal or an investigator visit). RESULTS: Of 8677 patients included, 44 patients were non-evaluable, leaving 8633 evaluable patients; 1347 patients reported SGAE (paracetamol: 14.5%, aspirin: 18.7%, ibuprofen: 13.7%). Completed diaries were returned by 98.5% of patients, and only 49 cases were lost to follow-up (0.6%). Almost all patients were contacted by telephone, 99.3% at the first call, and 98.5% at the second. Most SGAE were reported by patients; only 27 patients (2%) had a SGAE reported only by the GP. The tolerability rankings by treatment were consistent for all categories of SGAE: aspirin had the highest incidence of SGAE, and ibuprofen and paracetamol, lower, comparable incidences. CONCLUSIONS: A large, simple, randomised trial with patient-generated data can provide a sensitive source of information on AE, particularly in comparative safety assessments of OTC medications and other short-term therapies. This suggests reconsideration of the view that investigators are the most valid source for identifying and reporting AE.

Acetaminophen↗
PubMed2005

An easy to use method to approximate Poisson confidence limits.

Despite the ever larger choice of softwares and statistical packages allowing fast and accurate computation of binomial and Poisson confidence limits, there is always a need for a simple and reliable formula allowing non-computerized computations. The method proposed in this paper is derived from the Freeman and Tukey's variance stabilizing transformation for a random Poisson variable and adjusted for giving the best fit with the exact Poisson values. Despite its simplicity, allowing its use in any circumstances, this method provides very satisfactory results and a much better fit than classical formula based on the normal approximation, even if a continuity correction is used. It allows computation of Poisson confidence limits both for count or rates and proportions.

Biometry↗
PubMed2005

Fatigue, sleep restriction and driving performance.

We ran a randomized cross-over design study under sleep-deprived and non-sleep-deprived driving conditions to test the effects of sleep restriction on real driving performance. The study was performed in a sleep laboratory and on an open French highway. Twenty-two healthy male subjects (age = 21.5 +/- 2 years; distance driven per year = 12,225 +/- 4739 km (7641 +/- 2962 miles) [mean +/- S.D.]) drove 1000 km (625 miles) over 10 h during five 105 min sessions on an open highway. Self-rated fatigue and sleepiness before each session, number of inappropriate line crossings from video recordings and simple reaction time (RT) were measured. Total crossings increased after sleep restriction (535 crossings in the sleep-restricted condition versus 66 after non-restricted sleep (incidence rate ratio (IRR): 8.1; 95% confidence interval (95% CI): 3.2-20.5; p < 0.001)), from the first driving session. The interaction between the two factors (conditionxtime of day) was also significant (F(5, 105) = 3.229; p < 0.05). Increasing sleepiness score was associated with increasing crossings during the next driving session in the sleep-restricted (IRR: 1.9; 95% CI: 1.4-2.4) but not in the non-restricted condition (IRR: 1.0; 95% CI: 0.8-1.3). Increasing self-perceived fatigue was not associated with increasing crossings in either condition (IRR: 0.95; 95% CI: 0.93-0.98 and IRR: 1.0; 95% CI: 0.98-1.02). Rested subjects drove 1000 km with four shorts breaks with only a minor performance decrease. Sleep restriction induced important performance degradation even though time awake (8h) and session driving times (105 min) were relatively short. Major inter-individual differences were observed under sleep restriction. Performance degradation was associated with sleepiness and not fatigue. Sleepiness combined with fatigue significantly affected RT. Road safety campaigns should encourage drivers to avoid driving after sleep restriction, even on relatively short trips especially if they feel sleepy.

Adolescent↗
PubMed2005

Effects of armagnac or vodka on platelet aggregation in healthy volunteers: a randomized controlled clinical trial.

BACKGROUND: Cardiovascular mortality is especially low in southwest France (the French Paradox). In previous experimental studies, we found that alcohol-free extracts of armagnac could inhibit human platelet function in vitro and experimental thrombosis in vivo. To test the possible relevance of these findings, we tested the effects of daily use of small quantities of armagnac against same alcohol strength, polyphenol-free vodka in healthy volunteers. METHOD: Randomized controlled trial comparing 5-year old armagnac (30 ml/day for 2 weeks) to same alcoholic strength vodka, in 20 healthy volunteers, on platelet aggregation induced by ADP, collagen, and thrombin, as well as bleeding time, partial thromboplastin time (pTT), and plasma lipids during and after consumption. Platelet testing was done blind. RESULTS: After 14 days, ADP-induced platelet aggregation was inhibited more in armagnac (-31+/-3.2% compared to pretreatment values, p<.01) than in vodka (-11.0+/-6.8%, NS) users (p<.05, armagnac vs. vodka). A rebound increase of aggregation was found 2 weeks later in vodka but not in armagnac users. The same pattern was found for thrombin-induced aggregation, including post-treatment rebound. No effect was found on collagen-induced aggregation, bleeding time, pTT, or plasma lipids. CONCLUSION: The chronic ingestion of moderate quantities of armagnac modified platelet aggregation to ADP in healthy volunteers. The difference with the effects of same alcohol degree vodka is in favour of an effect of the nonalcoholic fraction in the effects of armagnac, rather than just alcohol. All spirits may not be equal for cardioprotection.

Adenosine Diphosphate↗
PubMed2005

Fatigue, sleepiness, and performance in simulated versus real driving conditions.

STUDY OBJECTIVES: To determine whether real-life driving would produce different effects from those obtained in a driving simulator on fatigue, performances and sleepiness. DESIGN: Cross-over study involving real driving (1200 km) or simulated driving after controlled habitual sleep (8 hours) or restricted sleep (2 hours). SETTING: Sleep laboratory and open French Highway. PARTICIPANTS: Twelve healthy men (mean age +/- SD = 21.1 +/- 1.6 years, range 19-24 years, mean yearly driving distance +/- SD = 6563 +/- 1950 miles) free of sleep disorders. MEASUREMENTS: Self-rated fatigue and sleepiness, simple reaction time before and after each session, number of inappropriate line crossings from the driving simulator and from video-recordings of real driving. RESULTS: Line crossings were more frequent in the driving simulator than in real driving (P < .001) and were increased by sleep deprivation in both conditions. Reaction times (10% slowest) were slower during simulated driving (P = .004) and sleep deprivation (P = .004). Subjects had higher sleepiness scores in the driving simulator (P = .016) and in the sleep restricted condition (P = .001). Fatigue increased over time (P = .011) and with sleep deprivation (P = .000) but was similar in both driving conditions. CONCLUSIONS: Fatigue can be equally studied in real and simulated environments but reaction time and self-evaluation of sleepiness are more affected in a simulated environment. Real driving and driving simulators are comparable for measuring line crossings but the effects are of higher amplitude in the simulated condition. Driving simulator may need to be calibrated against real driving in various condition.

Adult↗
PubMed2005

Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder.

Pre-clinical studies, active-control clinical trials and meta-analyses indicate that escitalopram (S-citalopram) might be more effective than citalopram, the racemic mixture of S- and R-citalopram. The present study aimed to confirm the superior efficacy of escitalopram over citalopram. A double-blind, randomized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram (20 mg/day) with citalopram (40 mg/day) over 8 weeks in outpatients with major depressive disorder (MDD) [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Primary efficacy parameter was change from baseline to last assessment in the MADRS total score. Out of 138 (aged 44.1+/-10.9 years; initial MADRS score 36.3+/-4.8) and 142 (aged 46.2+/-11.1 years; initial MADRS score 35.7+/-4.4) evaluable patients who were randomized to escitalopram and citalopram, respectively, six and 15 withdrew prematurely (P=0.05). The MADRS score decreased more in the escitalopram than in the citalopram arm (-22.4+/-12.9 versus -20.3+/-12.7; P<0.05). There were more treatment responders with escitalopram (76.1%) than with citalopram (61.3%, P<0.01). Adjusted remitter rates were 56.1% and 43.6%, respectively (P<0.05). Tolerability was similar in both groups. This randomized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD.

Adolescent↗
PubMed2005

Quantification of imatinib in human plasma by high-performance liquid chromatography-tandem mass spectrometry.

Imatinib, also known as Gleevec or Glivec, is a selective tyrosine kinase inhibitor currently used for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) and for other malignant pathologies. We have developed a LC-MS-MS [corrected] method that could be used for imatinib therapeutic drug monitoring in plasma. After a liquid-liquid extraction, the imatinib and its deuterated internal standard were eluted on an XTerra RP18 column with a gradient of acetonitrile-ammonium formiate buffer 4 mmol/L, pH 3.2. Imatinib was detected by electrospray ionization mass spectrometry with multiple reaction-monitoring mode. The calibration curves were linear over the range 10-5000 ng/mL. The limit of quantification was set at 10 ng/mL. The bias was lower than 8%. Intra-day and inter-day precisions were lower than 8%. The extraction recovery was higher than 90%. This method is simple, adapted to routine application, and allows accurate therapeutic monitoring of imatinib. It can be used to evaluate patient adherence to daily oral therapy, drug-drug interactions, or pharmacokinetic/pharmacodynamic relationships.

Antineoplastic Agents↗
PubMed2005

Cytotoxicity of abnormal Savda Munziq aqueous extract in human hepatoma (HepG2) cells.

Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation commonly used to treat diseases such as diabetes, cardiovascular diseases, chronic asthma and especially digestive cancer. Earlier studies have shown that ASMq is a free radical scavenger and could prevent mitochondrial and DNA oxidative damage. In this study, we tested the effects of aqueous extract of ASMq on human hepatoma cells (HepG2) to explore the possible mechanism of its putative anticancer properties. Aqueous extract of ASMq was tested on HepG2 proliferation (MTT assay) at 72 h, cell viability at 48 h (neutral red assay), lactate dehydrogenase release over 48 or 72 h as a measure of cytoplasmic leakage, lipid peroxidation (malondialdehyde-thiobarbituric acid adducts) at 48 h, and incorporation of [3H]-leucine, [3H]-thymidine and [3H]-uridine into cellular protein, DNA and RNA, respectively, at 24 or 48 h to assess the inhibition effects to cellular macromolecule synthesis. Our results showed a significant (P < 0.05) time- and concentration-dependent inhibition of HepG2 proliferation and viability, with increased cytoplasmic leakage, and time- and concentration-dependent inhibition of protein, DNA and RNA synthesis. No lipid peroxidation was found at these concentrations. The results of the present study suggest that the putative anticancer mechanisms of ASMq may at least involve cytotoxicity.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Increased heat shock protein 70 expression following toxicant-mediated cytotoxicity: a ubiquitous marker of toxicant exposure?

The up-regulation of heat shock protein (HSP) expression has been proposed as a general biomarker of cellular protection against various environmental stresses and chemicals. The present study investigated the possibility of using HSP70 up-regulation as a biomarker of toxicant exposure in vitro. Cells of a rat hepatoma cell line (FGC4) were exposed to concentrations of 1,3-dichloroacetone, duroquinone, diquat dibromide, menadione, hydrogen peroxide, cadmium chloride (CdCl2) and sodium (meta)arsenite (NaAsO2) that elicited 20-50% cytotoxicity over a 24-hour period, and HSP70 levels were measured by ELISA. Up-regulation of HSP70 expression was demonstrated following treatment with menadione, CdCl2 and NaAsO2, but not with the other chemicals tested. A shorter exposure time (6 hours) and/or the use of non-toxic concentrations reduced the level of HSP70 up-regulation with menadione, CdCl2 and NaAsO2, but did not uncover any up-regulation with the other chemicals. Although the toxicity of the majority of the chemicals tested is believed to involve an oxidative stress component, the results of this study clearly demonstrate that up-regulation of HSP70 expression cannot be used as a general biomarker of toxicant exposure in vitro.

Animals↗
PubMed2005

Potential impact of oral contraceptive choice on myocardial infarction mortality and deep vein thrombosis.

OBJECTIVES: To summarise the epidemiological evidence on the relationship between second- (OC2) and third-generation (OC3) oral contraceptives (OC) and the mortality associated with deep vein thrombosis (DVT) and myocardial infarction (MI), and to extrapolate and balance the evidence for these risks to the population of French OC users. METHODS: All studies published on the risk of MI during OC2 and OC3 use were analysed. For DVT the Committee for Proprietary Medicinal Products public assessment report published in 2001 and more recent studies published on this topic were used. The estimates of odds ratios (OR) for risk of death from DVT or MI were extracted from the published manuscripts. ORs were used to calculate the aetiological fraction of risk for death from DVT and MI in the population; the relative impact of OC3 compared to OC2 use was expressed as an excess risk of death overall and by age group for French women. RESULTS: Compared with OC2, the use of OC3 would prevent a maximum of 24 deaths from MI per year and induce a maximum of 16 deaths. Conversely, OC3 would induce 282-940 excess cases of DVT per year, resulting in 28-94 pulmonary embolisms and 3-19 deaths in the 4.7 million French OC users. CONCLUSION: Balancing the evidence, it is difficult to conclude that the overall cardiovascular risk is significantly lower for either of the two OC schemes.

Adult↗
PubMed2005

Atypical antipsychotics: from potassium channels to torsade de pointes and sudden death.

Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal dyskinesia) or the psychiatric disease itself. Cases have been described with most antipsychotics and have led to the withdrawal, temporary suspension from the market or restricted use of antipsychotics, such as sultopride, droperidol, sertindole or thioridazine. Reviewing the available data shows that all antipsychotics tested affect the cardiac potassium channel, with the concentration that produces 50% inhibition (IC50) ranging from 1 nmol/L (haloperidol) to 6 micromol/L (olanzapine). Experimental in vitro or in vivo electrophysiological studies have shown a dose-dependent increase in the duration of the action potential with various degrees of indicators of serious arrhythmogenicity. However, this does not always translate clinically into an increased duration of the QT interval or increased risk of torsade de pointes or sudden death in clinical trials or pharmacoepidemiological studies. In turn, QT prolongation in clinical trials does not always translate to an increased risk of torsade de pointes or sudden death. The reasons for these apparent discrepancies are unclear and could be related to insufficiently powered field studies, low plasma and tissue drug concentrations with reference to in vitro data or drug effects on other receptors or ion channels that have a protective effect. Alternatively, risks that were not apparent from preclinical or clinical data could be related to the use of the drug in high-risk patients, metabolic interactions or other factors that would only be encountered in large postmarketing populations. The assessment of cardiovascular safety, both preclinical and during premarketing clinical trials, needs to be supported by appropriately powered pharmacoepidemiology studies.

Animals↗
PubMed2004

Determination of myocardium to plasma concentration ratios of five antipsychotic drugs: comparison with their ability to induce arrhythmia and sudden death in clinical practice.

Reviewing available data shows that most of antipsychotic drugs are associated with arrhythmia and sudden death. Experimental studies have shown a HERG channel blockade, a dose-dependent increase in duration of action potential or of QT interval, with various degrees of indicators of serious arrhythmogenicity. However, it seems difficult to relate these in vitro and in vivo preclinical models to clinical findings, in part, because the relationship between concentrations used and in vivo tissue concentrations during treatment in man is not known. Consequently, we established the myocardium to plasma concentration ratios for a series of antipsychotic drugs by intraperitoneal administration of different level doses to the guinea pig. Then, we compared these values to their ability to induce arrhythmia or torsade de pointes in clinical practice. The myocardium to plasma concentration ratios were 2.2 for clozapine, 2.7 for olanzapine, 3.1 for sertindole, 4.5 for risperidone, and 6.4 for haloperidol. These data suggest that when the ratio is higher than 4, arrhythmia and sudden death may be expected. On the contrary, when the ratio is less than 3, little effect may be predicted. These results underscore the importance of interpreting HERG channel data and electrophysiological data in the context of other pharmacokinetic parameters such as myocardium to plasma distribution.

Animals↗
PubMed2004

Patterns and correlates of benzodiazepine use in the French general population.

OBJECTIVE: To investigate the prevalence of current use of benzodiazepines (BZDs) and related drugs in the French general population and factors associated with this use. METHODS: National cross-sectional telephone survey conducted between 25 April 2001 and 8 May 2001 in a representative sample of non-institutionalized adults of BZD use and duration, prescriber specialty, socio-demographic data and mood and anxiety disorders, using a structured diagnostic interview. RESULTS: The prevalence of current use of BZD was 7.5%. It was higher among women (9.7%) than men (5.2%). It increased with age and was higher in the jobless (10.9). Duration of BZD use was more than 6 months in 75.9% of users and increased with age. Of the 711 (17.7%) subjects with at least one mood or anxiety disorder, 122 (17%) used BZD compared with 180 (5.5%) of the 3296 subjects without mood or anxiety disorders. In multivariate analysis, factors associated with BZD use were age [odds ratio (OR): 3.6; 95% confidence interval (CI) 2.0-5.6], 6.5 (4.1-10.3) and 10.9 (6.9-17.1), respectively, for ages 35-44 years, 45-59 years and over 60 years compared with below 34 years, female gender (OR: 1.7; 95% CI 1.3-2.1), anxiety only (OR: 2.2; 95% CI 1.5-3.2), mood disorder only (OR: 4.4; 95% CI 2.7-7.1) or both mood and anxiety disorders (OR: 8.8; 95% CI 5.9-12.6). CONCLUSION: Despite precautions, warnings and attempts to limit use, there remains a high proportion of long-term BZD users in the general French population, especially in the elderly. Our findings add to the weight of opinion that messages concerning proper use of BZDs certainly need to be clarified and amplified.

Adult↗
PubMed2004

Fluvastatin reduces cardiac mortality in patients with coronary heart disease.

PURPOSE: To test the effectiveness of fluvastatin, 40-80 mg, in reducing the occurrence of cardiac and all-cause mortality in patients with coronary heart disease (CHD). METHODS: Meta-analysis of all clinical trials that assessed the effects of fluvastatin in CHD patients on major adverse cardiac events (MACE) as a prespecified endpoint was performed. A pooled analysis of four studies (n = 3525) was performed on an intent-to-treat basis. Clinical endpoints were the incidence, and time to first occurrence, of MACE (cardiac death, nonfatal MI, revascularization), noncardiac death, or all-cause death. Lipid parameters were also analyzed. RESULTS: Fluvastatin treatment significantly prolonged the time to cardiac death (p = 0.0174) and the time to cardiac death or nonfatal MI (p = 0.0055) compared with placebo. Fluvastatin significantly reduced the risk of any MACE (Cox risk ratio [RR], 0.85; 95% confidence interval [CI], 0.73-0.98), cardiac death (RR, 0.53; 95% CI, 0.31-0.90), cardiac death or MI (RR, 0.66; 95% CI, 0.49-0.89), all-cause death (RR, 0.65; 95% CI, 0.45-0.94) and all-cause death or MI (RR, 0.69; 95% CI, 0.53-0.90). Fluvastatin significantly lowered total cholesterol and low-density lipoprotein cholesterol levels and was well tolerated, with no cases of rhabdomyolysis in any of the studies assessed in the meta-analysis. CONCLUSIONS: This meta-analysis demonstrates clear beneficial effects of fluvastatin on cardiac and all-cause mortality in CHD patients, and supports the use of fluvastatin to reduce the incidence of MACE in a wide range of at-risk patients.

Aged↗