12 results on '"Hekster, Yechiel"'
Search Results
2. Influence of Chemical Structure on Hypersensitivity Reactions Induced by Antiepileptic Drugs: The Role of the Aromatic Ring.
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Handoko, Kim B., van Puijenbroek, Eugène P., Bijl, Annemarie H., Hermens, Walter A. J. J., Zwart-van Rijkom, Jeannette E. F., Hekster, Yechiel A., and Egberts, Toine C. G.
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ANTICONVULSANTS ,ALLERGIES ,DRUG side effects ,DRUG allergy ,DRUGS - Abstract
OBJECTIVE: Antiepileptic drugs (AEDs) can cause various idiosyncratic hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain symptoms of hypersensitivity. METHODS: Between January 1985 and January 2007, all adverse drug reactions (ADRs) reported to the Netherlands Pharmacovigilance Centre Lareb related to AEDs as suspected drugs were included in this study. ADRs were analysed using a case/non-case design. Cases were defined as those patients with ADRs involving symptoms of hypersensitivity. Non-cases were patients with all other ADR reports. Symptoms of hypersensitivity were classified according to the Gell and Coombs classification (type IIV) and the organ involved (e.g. cutaneous, hepatic). AEDs were classified as aromatic anticonvulsant if their chemical structure contained at least one aromatic ring. All other AEDs were classified as non-aromatic. We assessed the strength of the association between aromatic AEDs versus non-aromatic AEDs and reported hypersensitivity reactions with logistic regression analysis and expressed these as reporting odds ratios (RORs). RESULTS: In total, 303 cases of hypersensitivity associated with the use of AEDs were reported. Aromatic AEDs were suspected in 64.4% of these reports versus 41.3% (574/1389) of the non-hypersensitivity reports. A significant ROR of 2.15 (95% CI 1.63, 2.82) was found for aromatic AEDs and all hypersensitivity reactions. Aromatic AEDs were significantly associated with immunoglobin E-mediated type I hypersensitivity reactions (ROR 2.15; 95% CI 1.23, 3.78) and T-cell-mediated type IV reactions (ROR 6.06; 95% CI 3.41, 10.75). Type II and III reactions did not show an association. Cutaneous symptoms represented 39.9% of the hypersensitivity-related ADRs. Aromatic AEDs were significantly associated with cutaneous hypersensitivity reactions (ROR 5.81; 95% CI 3.38, 9.99). CONCLUSION: This study confirms that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains apparent idiosyncratic hypersensitivity reactions. Symptoms of hypersensitivity were reported twice as frequently with aromatic AEDs than with non-aromatic AEDs. Strong associations for aromatic AEDs versus non-aromatic AEDs were found for T-cell-mediated (type IV) reactions, as well as for cutaneous reactions. [ABSTRACT FROM AUTHOR]
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- 2008
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3. Therapeutic Drug Monitoring: An Aid to Optimising Response to Antiretroviral Drugs?
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Aarnoutse, Rob E., Schapiro, Jonathan M., Boucher, Charles A.B., Hekster, Yechiel A., and Burger, David M.
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DRUG monitoring ,DRUG analysis ,THERAPEUTICS ,HIV infections ,RETROVIRUS disease treatment - Abstract
Therapeutic drug monitoring (TDM) has been proposed as a means to optimise response to highly active antiretroviral therapy (HAART) in HIV infection. Protease inhibitors (PIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine satisfy many criteria for TDM. Nucleoside reverse transcriptase inhibitors (NRTIs) are not suitable candidates for TDM, since no clear plasma concentration-effect relationships have been established for these drugs. Several important limitations to the application of TDM for antiretroviral drugs should be recognised, including uncertainty about the best pharmacokinetic predictor of response and insufficient validation of target concentrations for individual PIs and NNRTIs. Data from two clinical trials support the use of TDM in treatment-naive HIV-infected patients who start with an indinavir- or nelfinavir-based regimen. TDM either prevented virological failures (presumably by preventing the development of resistance) or treatment discontinuations due to concentration-related toxicity. Application of routine TDM in other patient groups (treatment-experienced patients) or for drugs other than indinavir or nelfinavir (NNRTIs, other PIs, combination of PIs) is speculative at this moment. However, TDM can be used in selected patient groups (children, pregnant women, patients with renal or hepatic dysfunction) to confirm adequate drug concentrations, and for management of drug-drug interactions. TDM in treatment-experienced patients may be optimally used in conjunction with resistance testing. The integration of pharmacological and virological measures in the inhibitory quotient (IQ) needs to be standardised and elaborated further. TDM should be accompanied by careful assessment of adherence and can itself help identify non-adherence, although a drug concentration only reflects the last few drug doses taken by a patient. Additional clinical trials are needed before routine TDM can be adopted as standard of care in the treatment of HIV infection. [ABSTRACT FROM AUTHOR]
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- 2003
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4. The need for clinical pharmacy.
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Floor Schreudering, Annemieke, Alós Almiñana, Manuel, Hekster, Yechiel, Huon, Yvan, and Scroccaro, Giovanna
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- 2000
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5. Evaluation of drug treatment outcome in epilepsy: a clinical perspectiv.
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Schobben, Fred, Hekster, Yechiel, and van Zwieten Boot, Barbara
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For the approval of any new medicinal product quality, safety and efficacy are essential requirements. This manuscript focusses on the clinical development programme. For the investigation of antiepileptic drugs some international guidelines are of special importance. They are based on the knowledge of many experts and can be seen as a consensus on minimal requirements; deviations must be thoroughly justified. In phases II and III, usually randomised, double blind add on studies versus placebo in patients with therapy-resistant seizures are used to get an impression of the efficacy and certain safety issues. A clear dose-response relationship may be a good indication for efficacy. However, assessment of safety of the new product in add on studies is difficult. Therefore comparative phase III monotherapy studies versus established antiepileptic drugs are essential to confirm the results obtained in add on studies and are needed for a proper judgement of the efficacy/safety balance. The percentage of reduction of seizure frequency has played a dominating role as efficacy criterium. Nowadays preference is being given to the percentage responders. Which parameter is the most relevant for the given group of patients and what change is considered clinically relevant must be thoroughly argued. The definition of responder should focus on major benefit for the patients involved. [ABSTRACT FROM AUTHOR]
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- 1997
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6. Scenario analysis of the future of clinical pharmacy.
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Leufkens, Hubert, Hekster, Yechiel, and Hudson, Steve
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The role of clinical pharmacy in the health care system is changing rapidly. This change is almost universal among different countries and is related to developments in medical technology, health economics, informatics, socio economic status, and professional relations.Transitions to new systems of clinical pharmacy are difficult to anticipate. Even with well defined targets, it remains uncertain what the future of clinical pharmacy will bring us. The construction of plausible scenarios may help us better in preparing for the 'new world' ahead. At the annual congresses of ESCP in Prague 1995 (24th) and Lisbon 1996 (25th), a number of scenario analysis workshops with respect to the future of clinical pharmacy were organized. This paper gives a report of the results of these scenario sessions and reflects on the implications for future policy making. After we identified the driving forces behind the future of clinical pharmacy, various sets of assumptions were made and from them scenarios were constructed which are plausible: they 'could' happen. This analysis provided a logical framework in which we ultimately depicted three alternating stories of the future of clinical pharmacy, named 'CLERK', 'CONTROLLER' and 'CARE MANAGER'. These scenarios are intended to help clinical pharmasists to break free of familiar mental maps and to stimulate creative thinking on the future. [ABSTRACT FROM AUTHOR]
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- 1997
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7. Feasibility of an antibiotic order form. First experience in the department of internal medicine of a university hospital.
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Blok, Willem, Gyssens, Inge, Hekster, Yechiel, Koopmans, Peter, and Meer, Jos
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Inadequate control of antimicrobial drug use may lead to excessive expenditure for antimicrobial drugs and improper prescribing. It may also result in the emergence of multiresistant bacteria. An antibiotic order form may improve the quality of prescriptions by increasing the awareness of the physician of the antimicrobial spectrum needed (i.e. which microorganism is expected in a given patient), the desired duration of treatment, the potential need to adjust dosage, and the potential allergy of the patient to the drug. Furthermore, such an antibiotic order form facilitates prospective evaluation of both the quantity and the quality of prescribing practice. However, the introduction of yet another form to fill in may be met with opposition from prescribers. We have developed an easy-to-use antibiotic order form that incorporated the conventional medication order that was already in use in our hospital. Compliance (percentage of antimicrobial drug prescriptions for which an order form was used) was on average 58% in the first two weeks after introduction, and remained thereafter between 60% and 90%, varying between the different wards. Data retrieved from the antibiotic order forms could be used for surveillance. We conclude that this antibiotic order form was feasible in a large department of internal medicine of a university hospital. Future usefulness will depend on compliance and on personnel support for data processing and intervention. [ABSTRACT FROM AUTHOR]
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- 1996
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8. Analysis of total parenteral nutrition utilization in intensive-care patients.
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Frankfort, Ellen, Zimmerman, Cees, Borm, George, Dalen, Roelof, and Hekster, Yechiel
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The objective of this study is to validate an all-in-one defined daily dose (DDD) methodology for studying the utilization of total parenteral nutrition (TPN) with patient-linked data. Furthermore, the utilization of TPN in intensive-care patients is described. In a prospective survey, conducted from March to August 1992 on two intensive-care units, 47 patients using TPN were followed. Adapted ratios of prescribed daily dose (PDD) and DDD for amino acids, fat emulsion, and carbohydrates were 0.76±0.22, 0.69±0.30 and 1.07±0.23 (mean±SD), respectively. The ratio of the number of TPN DDD's to the number of TPN treatment days was 0.84±0.18. The prescription rate of TPN was 19.9 DDD/100 beddays, composed of 5.9 DDD/100 beddays for amino acids, 5.8 for fat emulsion, and 8.2 (or carbohydrates. It was shown that the proposed all-in-one DDD methodology can be used to describe the utilization of TPN and its components. The DDD's for amino acids, fat emulsion, and carbohydrates are valid for use in intensive-care patients. [ABSTRACT FROM AUTHOR]
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- 1994
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9. Utilization patterns of total parenteral nutrition in a university hospital.
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Frankfort, Ellen, Zimmerman, Cees, Dalen, Roelof, and Hekster, Yechiel
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To study the utilization of total parenteral nutrition, using methodology recommended by the World Health Organization, classification of components in accordance with the anatomical therapeutic chemical classification and defined daily dose system is necessary. Anatomical therapeutic chemical indices are available but defined daily dose values have not been established yet. In this article, a methodology to study both the total utilization of total parenteral nutrition, the utilization of individual substances and the composition of total parenteral nutrition is presented. To validate the proposed methodology, the utilization of total parenteral nutrition in a teaching hospital is studied, based on pharmacy computer data. The total utilization of total parenteral nutrition in the hospital in 1990 is 1.4 defined daily doses/100 beddays. The composition of total parenteral nutrition varied greatly between the clusters. In this study we showed that utilization of total parenteral nutrition can be measured with the proposed methodology, using a defined daily dose for total parenteral nutrition in concurrence with a defined daily dose for the individual components. [ABSTRACT FROM AUTHOR]
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- 1993
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10. Cost of hospital antimicrobial chemotherapy.
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Gyssens, Inge, Lennards, Christianne, Hekster, Yechiel, and Meer, Jos
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We will describe the method of cost-identification analysis, which was performed in a Dutch hospital during a review of antimicrobial drugs usage. In the present Dutch hospital budget system, in-patients' drug costs generate no revenues. Efforts to diminish drug costs result in financial benefit for the institution. To maximize cost containment, efforts are to be directed to all cost components. We chose wholesale purchase prices of antimicrobial drugs and national prices for salaries and hospital costs. Global cost comparison shows the most cost effective system of intravenous administration. Push injection is the most economic way to administer intravenous drugs which do not require dilution or prolonged infusion time. For stable solutions, such as metronidazole, ready-to-infuse bags are the most economic system. A global cost calculation is listed for commonly used antimicrobial drugs for in-patients. A cost comparison is given for vancomycin CP and teicoplanin, two antistaphyloccocal drugs, which are probably equieffective. The result of global cost comparison contributes to the decision to include new drugs into the hospital formulary or to replace older ones. [ABSTRACT FROM AUTHOR]
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- 1991
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11. Utilization patterns of non-steroidal anti-inflammatory drugs in an open Dutch population.
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Leufkens, Hubert, Ameling, Caroline, Hekster, Yechiel, and Bakker, A.
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Non-steroidal anti-inflammatory drugs represent an important drug class in ambulatory care. A utilization study among half a million persons showed that 8.6% could be identified as having used one or more non-steroidal anti-inflammatory drugs (excluding salicylates) in 1987. Data were drawn from a representative sample of pharmacy records which comprise full medication histories of individual patients. Overall utilization of non-steroidal antiinflammatory drugs was 10.8 defined daily doses/(1000 persons · day). Approximately three quarters of the patients are 'incidental' users and receive non-steroidal anti-inflammatory drugs for a relatively short time (30 days or less). Patients who were identified as 'regular' (31-210 days of therapy) and 'heavy' (>210 days of therapy) users, accounted for 21.2% respectively 4.8% of all users. 'Heavy' users are responsible for 17.3% of all non-steroidal anti-inflammatory drug prescriptions. Especially the elderly and females are prone to be 'heavy' users. Five drugs account for 90.4% of all prescriptions (diclofenac, ibuprofen, naproxen, piroxicam, indometacin). A total of 71.1% of the patients with more than one prescription for non-steroidal anti-inflammatory drugs switched in therapy. There are two classes of concomitant drug use especially relevant with respect to detecting non-steroidal anti-inflammatory drugs-associated risks: H blockers and antacids (belonging to anatomical therapeutic and chemical anatomic class A) and diuretics (belonging to anatomical therapeutical chemcial anatomic class C). More than half of the 'heavy' users showed concomitant use of drugs in these classes. [ABSTRACT FROM AUTHOR]
- Published
- 1990
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12. Neuropsychiatric symptoms during cefepime treatment.
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Diemont, Willem, MacKenzie, Marius, Sxhaap, Nicolaas, Goverde, Gerard, van Heereveld, Hedwig, Hekster, Yechiel, and van Grootheest, Kees
- Published
- 2001
- Full Text
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