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Biomedical subjects

A C G Egberts

Publications and source records attributed to A C G Egberts.

At least 19 recordsLinked to original sources
PubMed2006

VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement.

In a prospective follow-up study of the effects of VKORC1 and CYP2C9 genotypes on the anticoagulation status of patients, we assessed the CYP2C9 and the VKORC1 C1173T genotypes of patients during the initial 6 months of phenprocoumon treatment. We used linear regression models and Cox proportional hazard models to determine the effects of the VKORC1 and CYP2C9 genotypes on phenprocoumon dose requirements, overanticoagulation, and time to achieve stability. Allele frequencies of interest within the cohort (N=281) were 40.8% VKORC1 T-1173, 12.8% CYP2C9*2, and 6.9% CYP2C9*3. In patients with the VKORC1 CC genotype, carriers of a CYP2C9 polymorphism needed dosages that were nearly 30% lower than those for CYP2C9*1/*1 patients (P<0.001). In patients with a VKORC1 polymorphism, differences between carriers of a CYP2C9 polymorphism and CYP2C9*1/*1 were far smaller and largely not statistically significant. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (28.7% and 7.2%, respectively). Carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had a strongly increased risk of severe overanticoagulation (hazard ratio (HR) 7.20, P=0.002). Only carriers of a CYP2C9*2 allele had a decreased chance to achieve stability compared to CYP2C9*1/*1 patients (HR 0.61, P=0.004). In conclusion, the VKORC1 genotype modifies the effect of the CYP2C9 genotype on phenprocoumon dose requirements. A combination of polymorphisms of both genotypes is associated with a strongly increased risk of overanticoagulation, whereas delayed stabilization is mainly associated with the CYP2C9 genotype.

Aged↗
PubMed2006

Risk of ischemic complications related to the intensity of triptan and ergotamine use.

OBJECTIVE: To investigate whether the intensity of triptan and ergotamine use, in specific overuse, is associated with the risk of ischemic complications. METHODS: We conducted a retrospective nested case-control study using data from the PHARMO Record Linkage System. All patients with more than one prescription for either a triptan or ergotamine were initially identified. Cases were all patients who were admitted to the hospital for an ischemic complication. Matched controls were assigned the same index date as the cases. The determinant was the intensity of use of triptans and ergotamine during 1 year preceding the index date. Overuse was defined as use of > or =90 defined daily doses during that year. Conditional logistic regression was used to estimate odds ratios (ORs), adjusting for confounders. Stratified analysis was used to estimate the risk for both patients using and those not using cardiovascular drugs. RESULTS: A total of 17,439 patients received more than one prescription. A total of 188 cases and 689 controls were identified. Triptan overuse was not associated with an increased risk of ischemic complications (OR 0.96; 95% CI: 0.49 to 1.90). Overuse of triptans in patients concomitantly using cardiovascular drugs did not increase this risk. Overuse of ergotamine turned out to be a risk factor for ischemic complications (OR 2.55; 95% CI: 1.22 to 5.36). Patients overusing ergotamine and concomitantly using cardiovascular drugs were at highest risk (OR 8.52; 95% CI 2.57 to 28.2). CONCLUSIONS: In general practice, triptan overuse does not increase the risk of ischemic complications. Overuse of ergotamine may increase the risk of these complications, especially in those simultaneously using cardiovascular drugs.

Adolescent↗
PubMed2006

The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study.

The use of antipsychotics is associated with an increased risk of obesity. This consideration makes it important to search for determinants that can predict the risk for antipsychotic-induced obesity. In this cross-sectional study, we investigated whether polymorphisms in the HTR2C gene were associated with obesity (body mass index >30 kg/m2) in patients using antipsychotics. We examined polymorphisms in the promoter region of the HTR2C gene ((HTR2C:c.1-142948(GT)n, rs3813928 (-997 G/A), rs3813929 (-759 C/T), rs518147 (-697 G/C)) and an intragenic polymorphism (rs1414334:C>G). The results of the logistic regression were expressed as adjusted odds ratios (OR). In total, we included 127 patients mainly diagnosed with schizophrenia or schizoaffective disorder (89%). The results indicate that a combined genotype carrying the variant HTR2C:c.1-142948(GT)n 13 repeat allele, the common allele rs3813929 C, the variant allele rs518147 C and the variant allele rs1414334 C is significantly related to an increased risk of obesity (OR 3.71 (95% confidence interval: 1.24-11.12)).

Adult↗
PubMed2006

Indications for antidepressant drug prescribing in general practice in the Netherlands.

BACKGROUND: The intensity of the use of antidepressants in large populations can nowadays relatively easily be estimated using databases encompassing prescription data. There are shortcomings when using prescription databases as they contain no clinical data on patient illness. Antidepressants are prescribed for different illnesses, thus information on the indications could help when interpreting results from database studies on antidepressant drug use. The aim of this study is to investigate for which indications antidepressants are being prescribed in general practice in the Netherlands. METHODS: Data were obtained from the Second Dutch National Survey of General Practice, carried out by NIVEL (N=385,461). Patients, 18 years and older, who received an antidepressant prescription from a general practitioner in 2001 were selected (N=13,835). Indications for antidepressant drug prescribing were identified using time windows of different lengths. RESULTS: Antidepressants are most often being prescribed for depression (45.5%) and anxiety/panic disorders (17.2%). For these indications lengthening the time window around prescription date from 0 to 180 days resulted in an increase of 20-40% in antidepressant drug users identified with these indications. LIMITATION: None of our selected indications could be identified in the physician-patient contact file for about a third of the antidepressant drug users. The study was performed in a general practice setting and did not include antidepressant users who consult psychiatrists. CONCLUSION: GPs prescribe antidepressants predominantly for treating depression. However, using antidepressant drug as a proxy for identifying depressed patients in a prescription database should be done with caution and when possible in combination with clinical data.

Adolescent↗
PubMed2006

Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy.

OBJECTIVE: To study the association between use of antiepileptic drugs (AEDs) and risk of fractures. METHODS: The authors obtained data from the General Practice Research Database (GPRD). A case-control study was nested within a cohort of patients with active epilepsy. Cases were patients with a first fracture after cohort entry. Up to four controls were matched to each case by practice, sex, year of birth, timing of first epilepsy diagnosis, index date, and duration of GPRD history. Cumulative exposure to AEDs was assessed by summing the duration of all AED prescriptions. A distinction was made between AEDs that induce the hepatic cytochrome P-450 enzyme system and AEDs that do not. Medical conditions and drugs known to be associated with bone metabolism or falls were evaluated as potential confounders. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs. RESULTS: The study population comprised 1,018 cases and 1,842 matched controls. The risk of fractures increased with cumulative duration of exposure (p for trend < 0.001), with the strongest association for greater than 12 years of use: adjusted OR 4.15 (95% CI 2.71 to 6.34). Risk estimates were higher in women than in men. There was no difference between users of AEDs that induce and AEDs that do not induce the hepatic cytochrome P-450 system. CONCLUSIONS: Long-term use of AEDs was associated with an increased risk of fractures, especially in women. More research on mechanisms of AED-induced bone breakdown and female vulnerability to the effects of AEDs on bone health is warranted.

Accidental Falls↗
PubMed2006

Comparison of urine and oral fluid as matrices for screening of thirty-three benzodiazepines and benzodiazepine-like substances using immunoassay and LC-MS(-MS).

Benzodiazepines are the most frequently detected medicinal drugs in drivers. The use of benzodiazepines is associated with an increased road accident risk. In this study, the presence of benzodiazepines detected by liquid chromatography-(tandem) mass spectrometry [LC-MS(-MS)] in oral fluid and urine samples obtained from drivers stopped during a roadside survey was compared. In addition, the sensitivity and selectivity of enzyme multiplied immunoassay technique (EMIT II Plus) relative to LC-MS(-MS) was determined for both matrices. A total number of 1,011 urine samples were collected and screened for benzodiazepines using immunoassay (IA) (EMIT II Plus; cutoff 300 ng/mL). In the IA-positive (n = 25) and a group of randomly selected negative urine samples (n = 79), the presence or absence of benzodiazepines was confirmed by LC-MS-MS after deglucuronidation. The corresponding oral fluid samples (n = 101, 3 samples omitted), were analyzed by LC-MS(-MS) and IA (EMIT II Plus; cutoff 10 ng/mL). The presence of benzodiazepines was demonstrated by LC-MS-(MS) in all IA-positive urine samples, but in only four corresponding oral fluid samples. Concentrations in oral fluid were, one substance excepted, lower than in urine. The sensitivity and specificity of EMIT II Plus were better by using urine as matrix for screening of benzodiazepines than by using oral fluid. The results show that benzodiazepines are detectable in oral fluid. More research has to be done to determine the pharmacokinetic profile of the different benzodiazepines in oral fluid and to study the relationship between dose, concentration (in oral fluid and blood), and impairment.

Benzodiazepines↗
PubMed2006

Right-to-left shunt and migraine: the strength of the relationship.

Several studies have shown that the prevalence of a cardial right-to-left shunt (RLS) in patients with migraine with aura is significantly higher than in patients without migraine. To assess the strength of the possible relationship between RLS and migraine, the literature concerning this subject was systematically reviewed. We identified seven relevant studies. Among patients with RLS migraine with aura was 3.5 times more prevalent than among subjects without RLS [Mantel-Haenszel odds ratio (ORMH) 3.5; 95% confidence interval (CI) 2.1, 5.8]. In patients with ischaemic stroke migraine was more than two times more prevalent in patients with RLS than in patients without RLS (ORMH 2.1; 95% CI 1.6, 2.9). Our review shows that there is a clear association between RLS and migraine, especially migraine with aura. The relationship between RLS and migraine is further substantiated by the observations of disappearance and improvement of migraine symptoms after closure of the foramen ovale. However, the mechanism as well as the question about causality of this association has to be further elucidated.

Brain Ischemia↗
PubMed2006

Quality improvement of oral medication administration in patients with enteral feeding tubes.

BACKGROUND: The correct administration of oral drugs to patients on enteral tube feeding presents a special challenge. As patients are usually unable to swallow oral drugs and many drugs should not be crushed, ways have to be found to administer them through the feeding tube. Measures to improve the quality of oral drug administration in patients with enteral feeding tubes may consist of introducing guidelines, training nurses, or giving patient-tailored advice by the pharmacy. An integrated program comprising all these measures is likely to result in the greatest improvements. METHODS: A study was undertaken in two Dutch hospitals to investigate the effect of such an integrated program. RESULTS: The integrated program in hospital I resulted in a decrease in the number of tube obstructions (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.047 to 1.05). There was a significant decrease in the number of administration errors per nurse in hospital II (OR 0.003, 95% CI 0.0005 to 0.02). CONCLUSIONS: This multidisciplinary program comprising several interventions to promote the correct administration of drugs through an enteral feeding tube results in substantial improvements. As errors concerning administration of drugs to patients with enteral feeding tubes may lead to adverse drug events and loss of effect, these improvements are likely to contribute to a decrease in patient morbidity.

Data Interpretation, Statistical↗
PubMed2005

Cost-effectiveness of add-on lamotrigine therapy in clinical practice.

OBJECTIVE: This retrospective study addresses the cost-effectiveness of add-on therapy with lamotrigine in clinical practice. METHODS: Two years' observational data of 165 patients were used. Seizure frequency, adverse effects and direct medical costs were recorded for the year before and the year after the start of lamotrigine add-on therapy. Therapy effectiveness was measured by: (1) reduction in seizure frequency and (2) retention time. The incremental cost-effectiveness ratio expressed the direct medical cost per patient treated effectively with lamotrigine. RESULTS: The cost of medication was 492 (95% CI: 399-583) higher after the start of lamotrigine therapy. The extra cost of lamotrigine therapy (622) was partly offset by a reduction of the cost of co-medication (-130; 95% CI: -210 to -50). Overall, the total medical cost was 453 higher in the first year of lamotrigine therapy than in the year before the start of lamotrigine. Lamotrigine was effective in 47% of all the patients, making the resultant incremental cost-effectiveness ratio 954 per year. DISCUSSION: Add-on therapy of lamotrigine for patients with uncontrolled epilepsy offers improved health outcomes. Lamotrigine therapy is associated with increased cost (453) and an annual incremental cost-effectiveness ratio of 954. These data, together with utility data published in the literature, support the notion that lamotrigine should be considered as an add-on therapy in for patients with refractory epilepsy.

Adult↗
PubMed2005

Discontinuation symptoms in users of selective serotonin reuptake inhibitors in clinical practice: tapering versus abrupt discontinuation.

OBJECTIVE: Tapering of selective serotonin reuptake inhibitor (SSRI) therapy, as opposed to abrupt discontinuation, has been recommended by several guidelines and in the literature in order to diminish the occurrence of discontinuation symptoms. However, the evidence of a favourable effect of tapering is limited, and it is unclear how patients ought to discontinue SSRIs in daily life. The aim of this study was to examine the way in which patients discontinue SSRI therapy in clinical practice and to compare the effect of tapering with that of abrupt discontinuation on the occurrence of discontinuation symptoms. METHODS: Patients (n = 74) who recently discontinued SSRI therapy completed a questionnaire containing questions about discontinuation symptoms (DESS events), the prescribed SSRI, reasons for discontinuation, way of discontinuation, knowledge of discontinuation symptoms, impact on daily life and patient counseling and education. The number of DESS events was compared among groups (abrupt discontinuation versus tapering; age; male versus female; paroxetine versus other SSRIs; knowledge of discontinuation symptoms at start of therapy versus lack of knowledge). RESULTS: A total of 66 patients were eligible for analysis. Of all patients ending SSRI therapy, 21% abruptly discontinued therapy. There was a significant difference in the number of DESS events between abrupt discontinuation and tapering of SSRI therapy (12.0 versus 5.9). There was also a tendency for an adverse effect of lack of knowledge of discontinuation symptoms at the start of therapy on the number of DESS events (8.9 versus 5.5). CONCLUSION: One in five patients abruptly discontinued their SSRI therapy in clinical practice. Abrupt discontinuation caused a larger increase in the number of discontinuation symptoms than tapering. We therefore advise tapering SSRI therapy in clinical practice to prevent unnecessary adverse effects of discontinuation.

Adult↗
PubMed2005

Drug use and the severity of a traffic accident.

Several studies have showed that driving under the influence of alcohol and/or certain illicit or medicinal drugs increases the risk of a (severe) crash. Data with respect to the question whether this also leads to a more severe accident are sparse. This study examines the relationship between the use of alcohol, illicit drugs and/or medicinal drugs and the severity of an accident within a group of drivers that were involved in a crash in The Netherlands. Blood samples of 993 drivers, collected in the period from October 1998 through September 1999, were linked to accident characteristics as available from the National Transport Research Centre. The outcome measure was the severity of the accident. An accident was considered severe when the accident had resulted in hospital admission or death. All the blood samples obtained after the accident were screened for the presence of alcohol, illicit drugs (opiates, amphetamines and amphetamine-like substances, cocaine and metabolites, methadone, cannabinoids) and medicinal drugs (benzodiazepines, barbiturates and tricyclic antidepressants). The strength of the associations between exposure to the different classes of alcohol/drugs/medicines and the severity of the accident was evaluated using logistic regression analysis and were expressed as odds ratios (OR), adjusted for age, gender, time of the day, day of the week and urban area. The most frequently detected drugs were cannabinoids, benzodiazepines and cocaine. Our results showed no clear association between the use of alcohol, illicit drug and/or medicinal drug use and the severity of the accident. Given the process of obtaining blood samples from drivers involved in accidents and the retrospective nature of the study, we cannot rule out the occurrence of selection bias. Therefore, our findings need further confirmation.

Accidents, Traffic↗
PubMed2005

Recruitment of a cohort of lamotrigine users through community pharmacists: differences between patients who gave informed consent and those who did not.

OBJECTIVE: Community pharmacists may function as intermediaries in the recruitment of a population-based cohort of patients using specific drugs. In this study, baseline characteristics and the retention rate of patients that gave informed consent, refused and did not answer were compared. METHODS: A total of 1819 patients using the new antiepileptic drug (AED) lamotrigine were asked to provide informed consent for a retrospective chart study via their individual pharmacist. Four possible reactions resulted from the consent question: active consent, active refusal, passive refusal and non-informed. Patient characteristics and lamotrigine retention rate of the different groups were compared. RESULTS: Pharmacists did not inform a total of 183 patients (10%). Of the remaining patients, a total of 968 (59%) gave consent; 101 (6%) actively refused and 567 (35%) did not respond. Age, burden of illness, psychotropic co-medication and continuation of lamotrigine therapy were related to active consent. Lamotrigine retention rate in patients that gave consent was higher than in other patients. CONCLUSIONS: Patient recruitment with community pharmacists as intermediaries for observational studies on the effects of (new) drugs is feasible, and allows access to a broad population of patients. The recruitment procedure, however, may lead to selection bias.

Adolescent↗
PubMed2005

Effectiveness of lamotrigine in clinical practice: results of a retrospective population-based study.

OBJECTIVE: Evaluation of the effectiveness of lamotrigine in a population-based cohort of epilepsy patients. METHODS: Medical charts of 360 patients treated in 37 centres in The Netherlands were reviewed. Effectiveness of lamotrigine therapy was assessed during the first year of use, with patients serving as their own controls. Effectiveness was measured by reduction in seizure frequency and retention time. RESULTS: Effectiveness could only be assessed in 165 patients; assessment in remaining patients was not possible due to various reasons, such as insufficient medical chart information. Lamotrigine was effective in 40% of patients who had been prescribed lamotrigine because of insufficient seizure control (n=112), and 14% of these 112 patients became seizure free. Duration of epilepsy, baseline seizure frequency, valproate use, drug load and number of antiepileptic drugs (AED) used were related to effectiveness of lamotrigine. In this group, 36% continued lamotrigine (LTG) throughout the first year without experiencing a >50% seizure reduction. Lamotrigine was effective in 63% of patients who received the drug because of poor tolerability of other antiepileptic drugs (n=53). DISCUSSION: Lamotrigine is an effective drug in clinical practice. Use of retention time measures only may not correctly reflect the efficacy of antiepileptic drugs.

Adult↗
PubMed2004

Diffusion of the new antiepileptic drug lamotrigine in Dutch clinical practice.

INTRODUCTION: Lamotrigine is one of the recently introduced antiepileptic drugs (AEDs) licensed in the Netherlands in 1995. The objective of this study was to examine the diffusion of lamotrigine into clinical practice. Three different aspects of this diffusion process were examined: incidence of use, patient characteristics and changes in prescription patterns in the first 5 years following its introduction. METHODS: A retrospective follow-up study has been conducted using drug prescription data from the database of the Dutch Drug Information Project (GIP database). Patients were included who started with lamotrigine, carbamazepine, phenytoin or valproate in the period between January 1996 and December 2000. Incidence of use was calculated for the four drugs. Multiple logistic regression analysis was used to determine differences in baseline characteristics. The Chi-square test was used to analyse changes in the usage patterns of lamotrigine. RESULTS: The study population consisted of a total of 29,718 patients who were prescribed carbamazepine, phenytoin, valproate or lamotrigine for the first time in the study period. Carbamazepine and valproate accounted for the majority of all new prescriptions; the incidence of lamotrigine use remained stable with 4.4 patients per 100,000 per year. Baseline characteristics of lamotrigine differed depending on the patient's age and gender (OR 3.7, 95% CI 3.3-4.2; OR 1.4, 95% CI 1.3-1.5) relative to the conventional AEDs. In a large majority of cases, lamotrigine was used as a second-line or third-line AED. Physicians prescribing lamotrigine were predominantly neurologists, in contrast to prescribers of conventional AEDs. The prevalence of psychotropic medication and migraine-abortive drugs was significantly lower in users of lamotrigine than in users of conventional AEDs. During follow-up, several significant trends were noticed in the prescribing of lamotrigine with regard to age groups, gender, antiepileptic history and off-label use. DISCUSSION: Lamotrigine is prescribed to a population different from that using conventional AEDs. The uptake of lamotrigine in clinical practice is slow, for reasons probably related to characteristics of the drug itself and the prescribers. During the observation period, lamotrigine diffused gradually towards more first-line use as an AED and more off-label use.

Adolescent↗
PubMed2004

Quantitative analysis of 33 benzodiazepines, metabolites and benzodiazepine-like substances in whole blood by liquid chromatography-(tandem) mass spectrometry.

A quantitative method using high-performance liquid chromatography-mass spectrometry (LC-MS, ion trap) after matrix supported liquid-liquid extraction is described for the simultaneous determination in whole blood of 33 benzodiazepines including metabolites and benzodiazepine-like substances. The limits of detection (LOD) range from 0.0001 to 0.0126 mg/l. Linearity is satisfactory for all compounds. The extraction recoveries for the benzodiazepines in whole blood are between 60 and 91%, desmethyldiazepam, OH-bromazepam and brotizolam excepted. Selectivity, accuracy and precision are satisfactory for clinical and forensic purposes.

Benzodiazepines↗
PubMed2004

Increased psychotropic drug consumption by children in the Netherlands during 1995-2001 is caused by increased use of methylphenidate by boys.

OBJECTIVE: The aim of the study was to determine the changes in consumption of psychotropic drugs by children aged less than 18 years during the years 1995 to 2001 in the Netherlands. METHODS: The year prevalence of antipsychotics, benzodiazepines, antidepressants and psychostimulants for boys and girls under 18 years was determined using electronic pharmacy dispensing records obtained from the PHARMO database. RESULTS: The overall prevalence of psychotropic drugs increased from 11.1 per 1000 in 1995 to 22.9 per 1000 in 2001. This increase could almost completely be attributed to the increase in the use of psychostimulants, i.e. methylphenidate, which increased from 1.7 per 1000 children in 1995 to 10.0 per 1000 in 2001. For the other psychotropic drugs, no or only a small increase was seen. For both boys and girls, the use of psychostimulants was highest in the age group of 5-14 years. CONCLUSION: During the years 1995-2001, the consumption of psychotropic drugs by children in the Netherlands has more than doubled. This increase could largely be attributed to an increased use of the psychostimulant methylphenidate by boys of the age 5-14 years.

Adolescent↗
PubMed2004

Psychoactive substance use and the risk of motor vehicle accidents.

The driving performance is easily impaired as a consequence of the use of alcohol and/or licit and illicit drugs. However, the role of drugs other than alcohol in motor vehicle accidents has not been well established. The objective of this study was to estimate the association between psychoactive drug use and motor vehicle accidents requiring hospitalisation. A prospective observational case-control study was conducted in the Tilburg region of The Netherlands from May 2000 to August 2001. Cases were car or van drivers involved in road crashes needing hospitalisation. Demographic and trauma related data was collected from hospital and ambulance records. Urine and/or blood samples were collected on admission. Controls were drivers recruited at random while driving on public roads. Sampling was conducted by researchers, in close collaboration with the Tilburg police, covering different days of the week and times of the day. Respondents were interviewed and asked for a urine sample. If no urine sample could be collected, a blood sample was requested. All blood and urine samples were tested for alcohol and a number of licit and illicit drugs. The main outcome measures were odds ratios (OR) for injury crash associated with single or multiple use of several drugs by drivers. The risk for road trauma was increased for single use of benzodiazepines (adjusted OR 5.1 (95% Cl: 1.8-14.0)) and alcohol (blood alcohol concentrations of 0.50-0.79 g/l, adjusted OR 5.5 (95% Cl: 1.3-23.2) and >or=0.8 g/l, adjusted OR 15.5 (95% Cl: 7.1-33.9)). High relative risks were estimated for drivers using combinations of drugs (adjusted OR 6.1 (95% Cl: 2.6-14.1)) and those using a combination of drugs and alcohol (OR 112.2 (95% Cl: 14.1-892)). Increased risks, although not statistically significantly, were assessed for drivers using amphetamines, cocaine, or opiates. No increased risk for road trauma was found for drivers exposed to cannabis. The study concludes that drug use, especially alcohol, benzodiazepines and multiple drug use and drug-alcohol combinations, among vehicle drivers increases the risk for a road trauma accident requiring hospitalisation.

Accidents, Traffic↗