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Nicholas Moore

Publications and source records attributed to Nicholas Moore.

At least 55 records · Page 3Linked to original sources
PubMed2004

Differences between clinical trials and postmarketing use.

AIMS: Clinical trials constitute the gold standard to assess the efficacy and safety of new medicines. However, because they are conducted in standardized conditions far from the real world of prescription and use, discrepancies in patient selection or treatment conditions may alter both the effectiveness and risks. On the basis of three examples, our objectives were to study the differences between the characteristics of treated populations and treatment patterns in clinical trials and in postmarketing settings and to discuss the potential consequences on actual efficacy and safety. METHODS: Treated populations were compared with patients included in premarketing clinical trials. Comparisons were made on the basis of demographic characteristics and treatment patterns. RESULTS: Whatever the indicator and the drug studied, differences were observed: from 0.04% to 63% for tacrine, from 0% to 37% for celecoxib and from 6% to 52% for simvastatin, with possible consequences on the effectiveness and safety of the drug concerned. Our results confirm the under-representation of women and elderly patients in premarketing clinical trials, e.g. an M : F ratio of 4.6 in clinical trails of simvastatin vs 1.0 in the joint population. Moreover, the concomitant use of medicines was made extremely restrictive by the protocols of these trials while this was not the case in the postmarketing phase. This has possible consequences on the effectiveness and safety of the drug concerned. CONCLUSIONS: These results plead for systematic ad hoc observational postmarketing studies for any novel and/or expensive medicine to assess the relevance of premarketing data.

Adult↗
PubMed2004

Intravesical capsaicin versus resiniferatoxin for the treatment of detrusor hyperreflexia in spinal cord injured patients: a double-blind, randomized, controlled study.

PURPOSE: Chemical defunctionalization of C-fiber bladder afferents with intravesical vanilloids such as capsaicin (CAP) or resiniferatoxin (RTX) improves detrusor hyperreflexia in humans and animals. The little existing data comparing the efficacy and tolerance of these 2 vanilloid agents seem to favor RTX in 10% alcohol over CAP, which is usually diluted in 30% alcohol. We compared the efficacy and tolerability of the 2 vanilloid agonists in what to our knowledge is the first randomized, controlled study comparing nonalcohol CAP vs RTX in 10% alcohol in neurogenic patients with detrusor hyperreflexia. MATERIALS AND METHODS: This single center, randomized, double-blind, parallel groups study included 39 spinal cord injured adults with detrusor hyperreflexia. On day 0 patients were randomized to receive 1, 100 ml intravesical instillation of 100 nMol/l RTX diluted in 10% ethanol or 1 mmol/l CAP diluted in glucidic solvent. Efficacy (voiding chart and cystomanometry) and tolerability were evaluated during a 3-month followup. RESULTS: On day 30 clinical and urodynamical improvement was found in 78% and 83% of patients with CAP vs 80% and 60% with RTX, respectively, without a significant difference between the 2 treated groups. The benefit remained in two-thirds of the 2 groups on day 90. There were no significant differences in regard to the incidence, nature or duration of side effects in CAP vs RTX treated patients. CONCLUSIONS: Our results strongly argue for the importance of accounting for the role of vanilloid solute when interpreting the efficacy and tolerance of vesical vanilloid instillation in detrusor hyperreflexia cases. They suggest that a glucidic solute is a valuable solvent for vanilloid instillation.

Administration, Intravesical↗
PubMed2004

Age, performance and sleep deprivation.

Young subjects are frequently involved in sleep-related accidents. They could be more affected than older drivers by sleep loss and therefore worsen their driving skills quicker, or have a different perception of their level of impairment. To test these hypotheses we studied variations of reaction time (RT), a fundamental prerequisite for safe performing, as measured by lapses, i.e. responses > or = 500 ms and self-assessment of performance and sleepiness after a night awake and after a night asleep in a balanced crossover design in young versus older healthy subjects. Ten young (20-25 years old) and 10 older volunteers (52-63 years old) were tested with and without 24 h of sleep deprivation. Without sleep deprivation, RTs were slower in older subjects than in the younger ones. However, after sleep deprivation, the RTs of young subjects increased while that of the older subjects remained almost unaffected. Sleepiness and self-perception of performance were equally affected in both age groups showing different perception of performance in the age groups. Our findings are discussed in terms of vulnerability to sleep-related accidents.

Accidents, Traffic↗
PubMed2004

Protective effects of Munziq and Mushil of abnormal Savda to mitochondrial oxidative damage.

Munziq and Mushil of Abnormal Savda are traditional Uighur herbal medicinal products, which could have antioxidant properties protecting mitochondria against oxidative damage. Mitochondria were isolated from rat livers. A FeSO4/VitC hydroxyl radical-generating system was used to induce mitochondrial oxidative damage. Alterations in mitochondrial membrane structure were observed by electron microscopy, and mitochondrial superoxide dismutase (SOD) activity, malondialdehyde (MDA) level and Ca2+-Mg2+-ATPase activity were measured. Muziq or Mushil were added, at concentrations ranging from 10(-5) to 10(-1) g/mL. Mitochondrial membrane structure was damaged after exposure to hydroxyl radical; mitochondrial SOD and Ca2+-Mg2+-ATPase activities decreased (by 80 and 55%, respectively, both P < 0.01), and MDA level increased 4.6-fold (P < 0.01). Munziq and Mushil protected mitochondrial membranes from structural damage. They inhibited the changes in mitochondrial functions in a dose-dependent manner. At the highest concentrations, values were equal to initial normal values. Munziq and Mushil of Abnormal Savda can reduce the oxidative damage induced by hydroxyl radical and protect the mitochondrial membrane structure and its functions.

Animals↗
PubMed2004

Interactions between aspirin and COX-2 inhibitors or NSAIDs in a rat thrombosis model.

Recent in vitro studies, clinical trials and epidemiological studies have suggested possible interactions between aspirin and other cyclo-oxygenase (COX) inhibitors, such as ibuprofen of the COX-2 inhibitors celecoxib and rofecoxib. The objective of this study was to test the effects of aspirin (1, 2.5 and 5 mg/kg), and ibuprofen (4 and 15 mg/kg), diclofenac (2.5 mg/kg), flurbiprofen (2 mg/kg), celecoxib (7.5 mg/kg), and rofecoxib (1 mg/kg), alone or combined on a rat model of arterial thrombosis. Drugs were given orally daily for 7 days, before insertion of an arterio-venous shunt thrombosis system, left in place for 15 min. Main parameter was thrombus weight. Five to 12 rats were used per experiment, and 35 controls overall. Aspirin inhibited thrombus formation in a dose-dependent manner. All NSAIDS given alone also inhibited thrombus formation to approximately the same level as aspirin 1 mg/kg/day. Ibuprofen, celecoxib and rofecoxib inhibited the effects of aspirin, but not diclofenac or flurbiprofen. The interactions with aspirin do not seem to affect all NSAIDs to equal levels. The clinical impact of this needs to be confirmed in adequately powered clinical trials or pharmaco-epidemiological studies.

Administration, Oral↗
PubMed2004

Comparison of patient questionnaires and plasma assays in intentional drug overdoses.

Our aim was to explore the agreement between clinically collected information on purported drug intake and plasma data in intentional drug overdose. We included all subjects with intentional drug overdose above 15 years of age consecutively admitted to the Emergency Department of the University Hospital during 4 months. Information about drugs used and sources of this information was collected and compared to presence of drug in plasma, concerning four drugs with high toxic potential (tricyclic antidepressants, meprobamate, paracetamol and ethanol). Sensitivity, specificity, predictive positive and negative values of all sources of information pooled were assessed for each drug. 413 intentional drug overdoses were included, 66% with more than one drug. According to clinical information, 8% took tricyclic antidepressants, 11% meprobamate, 9% paracetamol and 41% ethanol. Systematic plasma assays confirmed this in 59% of cases for tricyclic antidepressants, 76% for meprobamate and ethanol, and 77% for paracetamol. Plasma concentrations were considered toxic in 28% of cases for tricyclic antidepressants, 65% for meprobamate, 43% for ethanol and never for paracetamol. Tricyclic antidepressants and meprobamate were found unexpectedly in 3%, paracetamol in 7% and ethanol in 6%. Toxic concentrations were found only with meprobamate. The risk of erroneous, clinically collected information was greater by excess (25 to 40% false positives) than by lack (3 to 7% false negatives). Thus, the consequences of erroneous, clinically collected information were probably more excess cost for the institution than medical risk for the patients. However these results found at the population level may not be true at an individual level.

Acetaminophen↗
PubMed2003

Effects of armagnac extracts on human platelet function in vitro and on rat arteriovenous shunt thrombosis in vivo.

INTRODUCTION: The "French paradox", a low cardiovascular mortality compared to the prevalent risk factors, has been attributed to the regular use of red wine, and to the polyphenols it contains. These have among other effects an antioxidant and antithrombotic effect. The French paradox is maximal in southwest France, a region which is the region of production of armagnac, an oak cask aged spirit also rich in polyphenols. METHOD: We tested the effects of a freeze-dried extract of 12-year-old armagnac (EA88) on in vitro human platelet adhesion, and on aggregation induced by collagen or ADP, in the presence or absence of hypoxanthine-xanthine oxidase (HX/XO), at concentrations ranging from 5 x 10(-9) to 5 x 10(-3) g/l, after 15-60 min incubation. We also tested the effects of 2-week oral treatment with 1, 5 and 25 mg/kg EA88 in a rat arteriovenous shunt thrombosis model. RESULTS: EA88 inhibited ADP-induced but not collagen-induced human platelet aggregation in vitro in a concentration- and incubation time-dependent manner, which was greater in the presence of HX/XO. In vivo, giving rats a daily oral dose of EA88 for 2 weeks inhibited thrombus formation in a dose-dependent manner, for doses consistent with the habitual human use of armagnac. CONCLUSION: Armagnac extract EA88 had an antiplatelet and antithrombotic effect that if confirmed in man could contribute to explain the intensity of the French paradox in southwest France.

Adenosine Diphosphate↗
PubMed2003

Fatigue, sleep restriction, and performance in automobile drivers: a controlled study in a natural environment.

OBJECTIVES: To test the neurobehavioral consequences of sleep restriction combined with fatigue from long-distance driving (1000 Km/600 miles). DESIGN: Counterbalanced study involving 3 experimental conditions: laboratory after controlled habitual sleep (8.5 hours), driving after controlled habitual sleep (8.5 hours) (Road 1), and driving after reduced sleep (2 hours) (Road 2). SETTING: Sleep laboratory and open French highway. PARTICIPANTS: 10 male participants (mean age 22 years, range 18-24 years, mean driving distance per year 15000 Km/9000 miles) free of sleep disorders. MEASUREMENTS: Simple reaction time, prospective self-assessment of performance, and instantaneous fatigue and sleepiness ratings measured at 2-hour intervals. RESULTS: A two-way repeated ANOVA with time of day and condition indicated a significant main effect for time of day (p < 0.05). The interaction between the two factors (condition * time of day) was also significant (p < 0.05). The effects of time of day were significant only in the condition of driving after sleep restriction, (p < 0.05). Under sleep restriction, some drivers presented an increase of 650 milliseconds compared to the laboratory condition, representing an increase of 23 meters in breaking distance at a speed of 75 miles per hour. Correlation analyses showed a significant linear correlation between self-assessment and reaction time in the laboratory condition (r = -0.58, p < 0.01) but not in the road conditions. Self-ratings during the breaks showed a significant increase in instantaneous self-rated fatigue and sleepiness between Road 1 and Road 2 conditions (Wilcoxon's test, Z = - 6.47, p < 0.0001 and Z = - 6.26, p < 0.0001). CONCLUSIONS: Sleep restriction combined with fatigue significantly affects reaction time. The lack of correspondence between reaction time and prospective self-evaluation of performance suggests that self-monitoring in real conditions is poorly reliable.

Adolescent↗
PubMed2003

Biases affecting the proportional reporting ratio (PPR) in spontaneous reports pharmacovigilance databases: the example of sertindole.

BACKGROUND: Automated measures of reporting disproportionality in databases of spontaneous reports of adverse drug reactions are an emerging tool to identify drug-related alerts. Sertindole, a new atypical neuroleptic known to prolong the QT interval, was suspended in November 1998 because the proportion of reports of fatal reactions suggesting arrhythmia among all reports with sertindole was almost ten times higher than that for other atypical neuroleptics in the UK. This excess risk was not predicted in preclinical data and had not been found in premarketing trials. METHOD: Reporting patterns over time were analysed. Prescription Event Monitoring (PEM) studies and a large retrospective cohort allowed for the comparison of actual death rates with atypical neuroleptics, and to assess which proportion of the deaths that occurred were reported. RESULTS: There were indications of possible skewing of reporting related to notoriety, surveillance and market size effects. Death rates in PEM studies were essentially similar between sertindole and other neuroleptics. Cardiac deaths had been two to three times more often reported than other causes of death. CONCLUSION: Proportional reporting ratios indicate differential reporting of possible reactions, not necessarily differential occurrence. There was no indication of an actual increase of risk of all causes or cardiac deaths during sertindole treatment, but only an increased risk of its being reported. The suspension of sertindole was rescinded by Committee on Proprietary Medicinal Products (CPMP) in October 2001.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Benzodiazepine utilization patterns in Alzheimer's disease patients.

BACKGROUND: Benzodiazepines (BZD) are commonly prescribed in the elderly. Persons with dementia may be at a greater risk of adverse reactions of BZD such as cognitive impairment. OBJECTIVE: To assess the prevalence of BZD use in Alzheimer's disease patients and to examine patient and drug-characteristics associated with this use. DESIGN: Cross-sectional study. PARTICIPANTS: Five thousand community-dwelling and institutionalized patients initiating a treatment with tacrine for a mild to moderate Alzheimer's disease and included in the tacrine-study (Paco cohort). MEASUREMENTS: Patient characteristics and BZD use recorded at the inclusion. MAIN OUTCOME: Use of BZD during the 3 months prior to inclusion. RESULTS: The 3-month prevalence of ever use of BZD was 20%. After controlling for age and gender, there was a non-significant inverse association between BZD use and a score of Mini-Mental Status Evaluation (MMSE) below 24 (OR: 0.88, 95% CI: 0.71-1.09), and significant inverse association with an increased number of chronic conditions (OR: 0.73, 95% CI: 0.58-0.91). Higher use of BZD was associated with higher level of overall drug consumption (OR: 2.3, 95% CI: 1.97-2.80). CONCLUSION: Alzheimer's disease patients are frequently prescribed BZD. A low score of MMSE (< 24) is associated with a decreased use of BZD. These results suggest important differences in BZD use patterns among persons with Alzheimer's disease.

Adult↗
PubMed2003

Effect of age of Armagnac extract and duration of treatment on antithrombotic effects in a rat thrombosis model.

In a previous study, we had shown that freeze-dried extracts of 12-year-old Armagnac could inhibit ADP-induced platelet aggregation in a dose- and duration-dependent manner, and reduce thrombus weight in an experimental rat arteriovenous shunt thrombosis model after 2-week oral treatment. Polyphenol content could however vary with age and origin of the brandy, and the onset and offset of the effect were not defined. To this end, we studied the effects of extracts of 5-, 10- and 15-year-old Armagnac from two different producers at 1, 5 and 25 mg/kg orally for 15 days, on the same rat arteriovenous shunt thrombosis model. We then studied the effects of 1, 3, 7 and 15 days of oral treatment with 5 mg/kg extracts of a 5-year-old Armagnac, and the effect 1, 3 and 7 days after a 1-week oral treatment of the same extract at the same dose. There was a dose-dependent decrease in thrombus weight, which was similar for both Armagnac origins for all ages. Extracts of 5- and 10-year-old Armagnac were similar, and more potent than extracts from 15-year-old Armagnac. There was a progressive decrease in thrombus weight over duration of treatment to 7 days, to about 50% of initial thrombus weight. The effect disappeared within 3 days after stopping a 7-day treatment. We confirm the dose-, age- and duration-dependent inhibition of arteriovenous shunt thrombosis in vivo by Armagnac extracts in rats.

Administration, Oral↗
PubMed2003

A simple method to estimate sample sizes for safety equivalence studies using inverse sampling.

Safety equivalence studies may be required to demonstrate that a new procedure or process is at least as safe as a previous one. They usually involve low or very low outcome rates that are often not precisely determined, making patient-based sample sizing uncertain. Using a reverse sampling approach, a method is derived from standard equations to estimate the number of events that need to be observed to demonstrate equivalence using the confidence interval approach. For instance, for a one-sided (nonsuperiority) hypothesis, 5% alpha risk, and 80% power, almost 100 events need to be observed in each study arm to demonstrate equivalence within 30%, or 250 events for 20% equivalence. The number of patients to be included can be derived directly from expected event rates.

Confidence Intervals↗
PubMed2003

High-performance liquid chromatographic method with diode array detection for identification and quantification of the eight new antidepressants and five of their active metabolites in plasma after overdose.

A high-performance liquid chromatographic method is described for the determination of selective serotonin reuptake inhibitors (fluvoxamine, paroxetine, sertraline, fluoxetine, citalopram, mirtazapine), serotonin norepinephrine reuptake inhibitors (milnacipram, venlafaxine), a noradrenergic and specific serotoninergic antidepressant (mirtazapine), and five pharmacologically active metabolites (desmethylcitalopram, didesmethylcitalopram, norfluoxetine, O-desmethylvenlafaxine, desmethylmirtazapine). After a double-step liquid-liquid extraction, compounds are separated on a Symmetry C8 column eluted with a gradient of acetonitrile-phosphate buffer 10 mM pH 3.8 and detected at 230 nm and 290 nm. Calibration curves were linear in the range 25 to 500 ng/mL (100-2000 ng/mL for venlafaxine and its metabolite). The limit of quantification was 25 ng/mL (100 ng/mL for venlafaxine and its metabolite). For all quality controls good accuracy was achieved (93% to 99.5%) with intraday and interday variation coefficients less than 12%. This method allows simple and rapid (run time 18 min) identification and quantification of the eight new antidepressants and five of their active metabolites. This method can be used for toxicologic purpose.

Antidepressive Agents↗
PubMed2003

Place of OTC analgesics and NSAIDs in osteoarthritis.

The risk related to the use of non-steroid anti-inflammatory drugs (NSAIDs) depends on the dose and duration of their use, in addition to the nature of the drug, and patient characteristics. The measures of risk and recent promotion of safer drugs have been mostly based on the results of clinical trials using continuous full-dose use of NSAIDs for periods up to 12 months which may not reflect real-life use and risks of the drugs. To assess this we did two studies of the utilisation of NSAIDs, one in a claims database to measure the amount of drugs dispensed to OA patients over 9 months, which showed that only a small fraction of patients actually bought enough analgesics or NSAIDs to cover the whole study period. On average, patients bought enough NSAIDs to cover 60 of 270 days. The second study was a survey of General Practitioners and rheumatologists to assess the number of users of NSAIDs seen over 2 days' consultations, the indications for and patterns of NSAIDs use. 11% of GP patients and 26% of rheumatologists' patients used NSAIDs, one-third for osteoarthritis (OA), about 8-10% for rheumatoid arthritis (RA) and the rest for various painful conditions. In OA and other conditions patients, more than 70% of patients had been taking their NSAIDs for less than 15 days at the time of consultation, whereas 42% of RA patients had been taking them for more than 6 months.

Journal Article↗
PubMed2003

Forty years of ibuprofen use.

Low-dose ibuprofen is as effective as aspirin and paracetamol for the indications normally treated with over-the-counter (OTC) medications and is associated with the lowest risk of gastrointestinal toxicity of any non-steroidal anti-inflammatory drug. By contrast, even low-dose aspirin is associated with an appreciable risk of gastrointestinal toxicity. Paracetamol is well tolerated and effective in treating mild to moderate pain but there is growing concern about a possible risk of gastrointestinal toxicity and a possible link with asthma in children. The PAIN (Paracetamol, Aspirin, Ibuprofen New tolerability) study was a blinded randomised comparison of the tolerability of OTC analgesics in the treatment of common types of acute pain encountered in the community. A total of 8,677 adults were randomised to treatment with ibuprofen 1200 mg/day, paracetamol 3 g/day or aspirin 3 g/day for 1-7 days. The most common indications for treatment were musculoskeletal conditions (31-33%), colds or flu (19-20%), backache (15-17%), sore throat (11-12%) and headache (10-11%). Significant adverse events were more common with aspirin (10.1%) than ibuprofen (7.0%) (P<0.001) or paracetamol (7.8%). Significant gastrointestinal events were less frequent with ibuprofen (4.0%) than with aspirin (7.1%, P<0.001) or paracetamol (5.3%) (P=0.025). For every 100 patients treated, five more will experience significant adverse events if they are taking aspirin rather than ibuprofen, and four more than if they were taking paracetamol.

Acetaminophen↗