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Biomedical subjects

Nicholas Moore

Publications and source records attributed to Nicholas Moore.

72 records · Page 4Linked to original sources
PubMed2002

Neuroleptics and mortality in schizophrenia: prospective analysis of deaths in a French cohort of schizophrenic patients.

OBJECTIVE: The putative role of neuroleptics in the known excess mortality of subjects with schizophrenia remains disputed. The aim of this study was to assess the link between mortality and the class of neuroleptic. METHOD: Causes of death (suicide, cardiovascular, etc.) and exposure to neuroleptics were studied in a cohort of 3474 patients with schizophrenia followed from 1993 to 1997. RESULTS: From 1993 to 1997, 178 patients died. The risk of all-cause death (OR=1.59; 95% CI 1.02-2.50; p=0.04), and suicide (OR=2.22; 95% CI 1.24-3.97; p=0.006) were increased in users of thioxanthenes (alone or associated with other drugs), and increased risk of "other causes" of death was associated with use of atypical neuroleptics (OR=2.06; 95% CI 1.15-3.70; p=0.0016). CONCLUSION: Our findings suggest the existence of association between certain classes of neuroleptics and death, all cause or specific. This could be related to the drug itself or to patient selection.

Adult↗
PubMed2002

In vivo and in vitro myocardial binding of risperidone and 9-hydroxyrisperidone.

Antipsychotic drugs have been found to prolong the QT interval, a phenomenon that, when severe, may facilitate the occurrence of complex ventricular arrhythmia such as torsade de pointes. Concentration-dependent QT prolongation has been demonstrated in vitro with such recent drugs as risperidone on Purkinje fibers and in isolated feline hearts. In vivo, there appears to be a relationship between plasma levels and QTc prolongation. This study was designed to estimate cardiac levels in vivo during treatment. For that purpose, we examined both in vivo and in vitro the ratio between plasma and cardiac tissue concentrations of risperidone and its active metabolite 9-hydroxyrisperidone. Binding parameters for different concentrations were determined in vitro by equilibrium dialysis. In vivo, they were determined by intraperitoneal administration of three doses in the guinea pig. Drug concentrations were determined by a high-performance liquid chromatography method with UV detection developed for that purpose. For risperidone, plasma protein binding varied from 67 to 43% and cardiac homogenate binding varied from 90 to 78%. 9-Hydroxyrisperidone values were lower. Tissue levels were 4.5-fold higher than plasma levels. Binding parameters were similar both in vivo and in vitro. From this model, the relevance of in vitro electrophysiological studies to clinical plasma concentrations can be approached.

Animals↗
PubMed2002

Benzodiazepine use and risk of dementia: a nested case-control study.

The objective of this article was to examine the possible association between benzodiazepine use and the risk of dementia in the elderly. This was a nested case--control study set in community settings in Bordeaux area, France. The participants were a representative sample of 3,777 elderly persons (65 years of age and older) followed from 1989 to 1997. The main outcome measures were the use of benzodiazepines in incident cases of dementia versus nondemented controls. On the basis of medical and psychological data, 150 patients were diagnosed with dementia according to the criteria of the third revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of patient's medicine chest by a trained neuropsychologist. After controlling for age, gender, education level, living alone, wine consumption, psychiatric history, and depressive symptomatology, ever use of benzodiazepines was associated with a significantly increased risk of dementia [adjusted odds ratio (OR), 1.7; 95% confidence interval, 1.2-2.4]. Former use was associated with a significantly increased risk of dementia (adjusted OR, 2.3; 95% CI,1.2-4.5). No association was found between dementia and the current use of benzodiazepines (adjusted OR, 1.0; 95% CI, 0.6-1.6). Our finding suggest that former use of benzodiazepines could be a risk factor for dementia, but more detailed investigation are needed.

Aged↗
PubMed2002

High-performance liquid chromatographic method for the simultaneous determination of the six HIV-protease inhibitors and two non-nucleoside reverse transcriptase inhibitors in human plasma.

A selective and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the determination of the six human immunodeficiency virus (HIV)-protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) and the non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) in a single run. After a liquid-liquid extraction with diethyl ether, the six protease inhibitors and the two non-nucleoside reverse transcriptase inhibitors are separated on a Stability RP18 column eluted with a gradient of acetonitrile and phosphate buffer 50 mmol/L pH 5.65. A sequential ultraviolet detection (5-minute sequence set at 240 nm for nevirapine acquisition, 22-minute sequence set at 215 nm for other antiretroviral drugs acquisition followed by a sequence set at 260 nm for internal standard acquisition) allowed for simultaneous quantitation of the six protease inhibitors, nevirapine, and efavirenz. Calibration curves were linear in the range 100 ng/mL to 10,000 ng/mL. The limit of quantitation was 50 ng/mL for all drugs except nevirapine (100 ng/mL). Average accuracy at four concentrations ranged from 88.2% to 110.9%. Both interday and intraday coefficients of variation were less than 11% for all drugs. The extraction recoveries were greater than 62%. This method is simple and shows a good specificity with respect to commonly co-prescribed drugs. This method allows accurate therapeutic monitoring of amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, efavirenz, and nevirapine.

Alkynes↗
PubMed2002

Pharmacokinetic interaction between high-dose methotrexate and oxacillin.

An 18-year-old man received two high-dose methotrexate cycles for the treatment of an osteosarcoma. Fifteen grams of methotrexate were infused over 6 hours. During the second cycle, co-administration of oxacillin (1g/8h) resulted in prolonged and marked elevation of methotrexate plasma concentrations. The patient experienced acute toxicity with renal failure, myelosuppression, mucitis, fever, and dermatologic abnormalities. After an initial improvement with folinic acid rescue and hemodialysis, the patient died. Oxacillin may thus inhibit the elimination of methotrexate.

Adolescent↗
PubMedDate not supplied

The safety of drugs for OTC use: what evidence is required for an NSAID switch?

In recent years there has been a growing demand for safe and effective over-the-counter (OTC) drugs. The demonstration of the safety of OTC products in actual conditions of use is crucial for their wide distribution, since the circumstances of their use may be different from the prescription-only setting. A group of experts met in Geneva, Switzerland, with the aim of exploring the criteria required to show safety equivalence of OTC medications, with specific reference to low-dose non-steroidal anti-inflammatory drugs (NSAIDs) used for analgesia. It was agreed that an acceptable surrogate marker for safety as the primary endpoint in a study designed to show that a new NSAID was not inferior to a current NSAID would be any adverse event leading the patient to consult a physician. A sample size of 10,000 patients in each arm of a two-arm study would be sufficient to show non-inferiority with acceptable relative risk equal to 1.2 with at least 90% power for an event rate of 5%. An example of a possible pharmacy-based randomized study design to demonstrate safety equivalence of OTC analgesics is given.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Risk factors for adverse events in analgesic drug users: results from the PAIN study.

BACKGROUND: The relative influence of various risk factors for adverse events (AE) in analgesics users have never been precisely quantified. Advantage was taken of data generated in the paracetamol, aspirin and ibuprofen new tolerability (PAIN) study, a large randomized double-blinded trial of paracetamol, aspirin or ibuprofen for common pain in general practice to attempt this. OBJECTIVE: Identify and quantify factors associated with the occurrence of AE in users of analgesic drugs. METHOD: Multivariate logistic regression analysis of potential risk factors for all AE, clinically significant AE (SAE) and clinically significant gastro-intestinal AE (GI SAE). RESULTS: Of the 8677 patients included in the study, 8633 contributed data. The main risk factors for SAE were indication: compared to those treated for musculoskeletal pain, patients treated for menstrual pain had an odds ratio (95% Confidence Interval) of 0.4 (0.2-0.7), sore throat 0.6 (0.5-0.8), cold and flu 0.7 (0.6-0.8), headache 0.8 (0.7-1.0); concomitant use of medication contra-indicated in the drugs' labeling (OR: 2.2; 1.6-2.9); increasing number of other concomitant medications: 1: OR 1.5 (1.3-1.8); 2-3: OR 1.9 (1.6-2.3); more than 3: OR (2.7; 2.1-3.5); treatment with aspirin: OR 1.4; (1.2-1.6) but not ibuprofen: OR 0.9; (0.8-1.1) compared to paracetamol; history of previous GI disorder OR 1.4 (1.0-1.8); female gender: OR 1.3 (1.1-1.4). Age was not significantly associated with AE in the multivariate analysis. Risk factors for all AE and GI SAE were mostly the same as for significant AE, but there were fewer GI SAE with ibuprofen than with paracetamol (OR 0.8; 0.6-0.9). CONCLUSION: Apart from the analgesic used and its indication, the main risk factors identified for AE in users of first-line analgesics for common pain were the number and nature of concomitant medication.

Acetaminophen↗
PubMedDate not supplied

A simple method for the determination of ethylene-thiourea (ETU) in biological samples.

A direct, simple, and rapid high-performance liquid chromatographic method has been developed for the determination of ethylene-thiourea (ETU) in biological fluids. Samples were chromatographed on a Lichrosorb RP8 (5 pm) column after extraction with dichloromethane. The mobile phase was a mixture of hexane/isopropyl alcohol/ethyl alcohol (93:6:1 v/v) added with 0.6 mL/L butylamine. Detection was done with a UV detector set at 243 nm. This method was validated to standard criteria. Calibration curves for ETU in 100 microL of 0.9% saline, 500 microL plasma, and 10 mL urine were linear (r2 > 0.99) from 0.05 to 30 microg/mL, 0.025 to 30 microg/mL, and 1 to 100 ng/mL, respectively. The lower limit of detection was 20 ng/mL in plasma, 25 ng/mL in 0.9% saline, and 0.5 ng/mL in urine.

Animals↗
PubMedDate not supplied

Identification and quantitation by high-performance liquid chromatography of mancozeb following derivatization by 1,2-benzenedithiol.

Ethylenebisdithiocarbamate (EBDC) fungicides are the most important class of organic fungicides and exhibit a high degree of carcinogenicity, mutagenicity, and neurotoxicity. For that reason, the safe application of these fungicides in practice requires a convenient method for their determination, applicable to biological fluids. We describe a high-performance liquid chromatography (HPLC) assay. After elimination of the metal which defines the product (maneb, mancozeb, zineb.) with EDTA, the resulting EBDC is derivatized with 1,2-benzenedithiol to yield a cyclocondensation product, 1,3-benzodithiole-2-thione, which can then be quantitated by reversed-phase HPLC at 365 nm using a microBondapak C18 column. The mobile phase was methanol/H2O (70:30, v/v). The assay was linear from 0.25 to 100 microg/mL. Within- and between-day precision and accuracy for this assay were better than 9% and 6%, respectively. The lower limits of detection and quantitation were estimated to be 0.1 and 0.25 microg/mL, respectively. This simple new method has been applied to determine mancozeb concentration in rat urine samples from urinary excretion studies.

Animals↗
PubMedDate not supplied

[Real-life use of inhaler devices for chronic obstructive pulmonary disease in primary care].

The correct use of inhalation devices is an inclusion criterion in many comparative studies. However, patients can make errors, thus compromising the effectiveness of their own inhaler. The aim of the study is to evaluate inhaler use by patients with chronic obstructive pulmonary disease (COPD) [n = 984]. General practitioners assessed inhalation technique, using a specific checklist previously established for each inhaler model (Aerolizer, Autohaler, Diskus, a pressurised metered-dose inhaler (pMDI) or a Turbuhaler). A total of 24% of the patients using a pMDI did not make an error compared with 34-40% of those using breath-actuated devices. The frequency of critical errors varied according to the device: 11.5-14.9% of the subjects using an Aerolizer, Autohaler or Diskus versus 37.4% and 38.1% of the patients using a pMDI and a Turbuhaler, respectively. The proper use of the Turbuhaler is often overestimated (24.7%) compared with the pMDI (2.1%). The development of educational programmes for patients and prescribers is needed to improve the management of COPD.

Aged↗
PubMedDate not supplied

NSAID use profiles derived from reimbursement data in France.

Because extrapolation of adverse event rates from clinical trials to the general population relies on the assumption of similar drug-usage patterns, we have studied usage patterns for nonsteroidal anti-inflammatory drugs (NSAIDs) from the National Health Insurance claims database. Reimbursement patterns of NSAIDs and analgesics were studied in a cohort of 232 users, half selected from authorisations of reimbursed spa cures, and the other half - strictly matched according to age and gender - who had redeemed at study onset at least one prescription for NSAIDs, analgesics or other antirheumatic drugs. Drug utilisation was measured as the total number of defined daily doses (DDD) bought over the 9-month study period. Over this time, the patients bought a median 45 DDD of NSAIDs out of the 270 needed to cover the whole period. Only two patients bought 270 DDD or more. Median paracetamol use (alone or combined) was 26 days. This study shows that patients use NSAIDs either intermittently or at lower than recommended doses, which is consistent with a primarily symptomatic use. Intermittent or on-demand use of NSAIDs, or at doses lower than full, could partly explain the lower rates of gastrointestinal bleeding and other ulcer complications in postmarketing epidemiological studies than could be expected from the findings of clinical trials.

Adult↗
PubMedDate not supplied

[Celecoxib prescription: data from the "Sécurité Sociale" database of the Aquitaine Region, South-Western, France].

OBJECTIVE: The objective of this study was to describe the characteristics of subjects beginning celecoxib treatment and the evolution of treatment over a 6-month period. METHODS: All the subjects (n = 14 323) for whom reimbursement of celecoxib was submitted to the "Sécurité Sociale" d'Aquitaine in December 2000 were included in the study. Their mean age was 61.9 years, and the male/female sex ratio was equal to 0.45. Almost two-thirds of the subjects were previous typical nonsteroidal anti-inflammatory drug users (NSAIDs-typical). RESULTS: Fifteen percent of the subjects had a gastroprotective agent prescribed, either on the same form as celecoxib or during the following 30 days. New reimbursements of celecoxib involved 41% of the subjects. Among the subjects who received a repeat prescription of celecoxib, 41% had used a gastroprotective agent at least once during the 6 months before study inclusion and 44% during the 6 months after inclusion. Among the subjects who did not renew their celecoxib prescription, the respective proportions were 32.2% and 33.7%. DISCUSSION: These results show that celecoxib is mainly prescribed to previous NSAIDs-typical users. The small difference in the prescription of gastroprotective agents between the period preceding and that following the initiation of celecoxib treatment does not indicate an advantage of celecoxib in terms of a lower rate of use of gastroprotective agents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

[Antidepressant adverse effects in the elderly: analysis of spontaneous reports in France].

The prescription of antidepressants in the elderly has changed since the marketing of new antidepressants such as selective serotonin reuptake inhibitors (SSRIs). We analysed the adverse effects associated with antidepressants in subjects aged > or =75 years reported to the pharmacovigilance centres in France. Among the 2381 cases recorded between 1985 and 2001, the distribution of adverse effects may reflect sales figures: 1040 for SSRIs (44%), 586 for tricyclic and related antidepressants (25%), 46 for monoamine oxidase inhibitors (2%) and 654 for other antidepressants (27%). Adverse effect patterns differed according to antidepressant class. For SSRIs, hyponatraemia was predominant (30%), followed by psychiatric (13%) and nervous system (10%) effects. For tricyclic antidepressants, psychiatric effects (confusion, agitation) [21%] were the most frequent followed by cardiovascular effects (15%). However, the consequences of adverse effects such as hyponatraemia are far from negligible in the elderly.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

Less use of NSAIDs in long-term than in recent chondroitin sulphate users in osteoarthritis: a pharmacy-based observational study in France.

In clinical trials, long-term use of a specific chondroitin sulphate, Chondrosult 400 (CS400) has demonstrated symptomatic efficacy in osteoarthritis comparable to that of nonsteroidal anti-inflammatory drugs (NSAIDs) with significantly fewer side-effects. CS400 could therefore reduce the use of and risks associated with NSAIDs. A cross-sectional observational study was therefore devised in 199 randomly selected pharmacies in France to verify the concomitant use of analgesic and NSAIDs medication in patients prescribed CS400. Consecutive patients filling a prescription for CS400 were prospectively recruited and classified into recent users (3 months or less of continuous use) and long-term users (more than 3 months of continuous use) of CS400. The main outcome measure was current and long-term use of analgesics and NSAIDs. The 844 participating patients included 623 (73.8%) women and 221 (26.2%) men. Mean age was 65.9 years. Ninety eight (11.6%) patients did not use any analgesic or NSAIDs for osteoarthritis: 746 (88.4%) reported the use of at least one of these drugs. Compared to recent users, long-term users of CS400 had a significantly lower current (44.4 versus 52.5%, p < 0.05) and long-term use of NSAIDs (11.8% versus 18.5%, p < 0.05), and of analgesics (70.3 versus 79.3%, p < 0.01).

Aged↗