PubMed Health⌕ Search

Biomedical subjects

J Krska

Publications and source records attributed to J Krska.

18 recordsLinked to original sources
PubMed2002

Patient reporting of potential adverse drug reactions: a methodological study.

AIMS: To develop a systematic generic method of enabling patients to report symptoms which they believe to be due to a particular prescribed drug. METHODS: A piloted body system-based questionnaire was distributed to patients registered with 79 medical practices in Grampian prescribed one of nine recently marketed 'black triangle' drugs. These comprised four antidepressants, three antiepileptics and two analgesics. This requested respondents to identify any symptoms experienced over the previous year which they thought could be due to the 'black triangle' drug they had used. A sample of medical records was examined to compare symptoms recorded with those reported by patients. A classification system was developed for the study to enable the assessment of symptoms reported for their potential relationship to patients' drug therapy. All symptoms reported were classified, taking into account information provided by patients on their concomitant drugs and diseases. A specialist pharmacist independently re-classified a sample of the symptoms to validate the process. RESULTS: A 36.3% response rate was obtained (837/2307) with 742 respondents (88.6%) reporting at least one symptom. The median per patient was 6.0 (range 0--71), with almost half (406, 48.5%) reporting fewer than five symptoms. Most symptoms (71.0%) were classified as being probably or possibly related to the drugs studied. Agreement between researcher and specialist on the classification of 75.3% of 716 symptoms was obtained (Kappa=0.563). Responses from patients prescribed antidepressant drugs were more likely to include symptoms potentially caused by these drugs (74.5% of all symptoms reported) than those from patients prescribed analgesics (67.4%) or antiepileptics (65.1%, chi2 = 23.858, d.f. = 2, P < 0.001). Patients reporting large numbers of symptoms were more likely to report some which were classed as unlikely to be an ADR or unattributable (chi2 = 80.587, d.f. = 3, P < 0.001). Of the 742 reporting symptoms in questionnaires, 402 (54.2%) claimed to have reported some or all of these to their doctor. Only 162 (22.6%) of 716 patient-reported symptoms were documented in the primary care medical records of 103 patients prescribed tramadol or venlafaxine. CONCLUSIONS: Respondents were clearly willing to report symptoms, the majority of which were classed as possibly/probably related to the drugs studied. The results suggest that patients do not report all symptoms they suspect to be ADRs to their GP and that GPs do not record all symptoms which may be reported to them. The method could help to identify problems which patients perceive as being related to their drug therapy and contribute to increased ADR reporting.

Adverse Drug Reaction Reporting Systems↗
PubMed2001

Pharmacist-led medication review in patients over 65: a randomized, controlled trial in primary care.

BACKGROUND: regular medication review has been recommended for those over 75 and those on multiple drug therapy. Pharmacists are a potential source of assistance in reviewing medication. Evidence of the benefits of this process is needed. OBJECTIVE: to study the effect of medication review led by a pharmacist on resolution of pharmaceutical care issues, medicine costs, use of health and social services and health-related quality of life. DESIGN: randomized, controlled trial. SETTING: general medical practices in the Grampian region of Scotland. SUBJECTS: patients aged at least 65 years, with at least two chronic disease states who were taking at least four prescribed medicines regularly. METHODS: pharmacists reviewed the drug therapy of 332 patients, using information obtained from the practice computer, medical records and patient interviews. In 168 patients, a pharmaceutical care plan was then drawn up and implemented. The 164 control patients continued to receive normal care. All outcome measures were assessed at baseline and after 3 months. RESULTS: all patients had at least two pharmaceutical care issues at baseline. Half of these were identified from the prescription record, the rest from notes and patient interview. Of all the issues, 21% were resolved by information found in notes and 8.5% by patient interview. General practitioners agreed with 96% of all care issues documented on the care plans in the intervention group. At the time of follow-up, 70% of the remaining care issues had been resolved in the intervention group, while only 14% had been resolved in the control group. There were no changes in medicine costs or health-related quality of life in either group. There were small increases in contacts with health-care professionals and slightly fewer hospital admissions among the intervention group than the control group. CONCLUSIONS: pharmacist-led medication review has the capacity to identify and resolve pharmaceutical care issues and may have some impact on the use of other health services.

Aged↗
PubMed2000

Drug utilization evaluation of nonprescription H2-receptor antagonists and alginate-containing preparations for dyspepsia.

AIMS: To evaluate the use, efficacy and adverse effects of nonprescription H2-receptor antagonists and alginate-containing preparations obtained from community pharmacies. METHODS: Questionnaires were distributed to customers from 39 pharmacies in Scotland and Wales. RESULTS: Of 767 customers recruited, 608 (79.3%) returned an initial questionnaire and 472 (61.5%) customers a second questionnaire. The vast majority of respondents (424, 69.7%) had suffered their symptoms on three or more occasions and 369 (60.7%) had previously tried medicines to relieve their symptoms. Referrals to a doctor were less frequent than recommended in guidelines and few of those who were referred actually saw a doctor. Over a quarter of those returning the second questionnaire claimed to be taking more than one product simultaneously for symptom control. Eight customers who were taking prescribed ulcer-healing drugs obtained H2-receptor antagonists. The majority of respondents (355/472, 75. 2%) obtained some or complete symptom relief using the product obtained and 369/472 (78.2%) were completely satisfied with their product. H2-receptor antagonists were more likely to produce complete relief of symptoms than alginate-containing preparations (P < 0.05). Only 14 respondents (3.0%) reported side-effects from the product used which were mostly gastro-intestinal. CONCLUSIONS: The study demonstrated that drug utilization studies are feasible to carry out in a community pharmacy setting. While the results support published evidence of the efficacy and minimal toxicity of these products, they also highlight the possibility of H2-receptor antagonists being used outwith their licenced indications.

Adult↗
PubMed1999

Withdrawal of peripheral vasodilators in primary care.

AIMS: To investigate the use of peripheral vasodilators in selected practices in primary care and to observe the effect of withdrawing therapy in a sample of patients. METHODS: Patients receiving repeat prescriptions for peripheral vasodilators, identified from two practices in Grampian, were interviewed prior to and following withdrawal of therapy. RESULTS: Of the 35 patients, review of the continued need for therapy was documented in the medical notes of only one patient. Treatment was successfully withdrawn from 17 patients, generating considerable savings. CONCLUSIONS: Review of peripheral vasodilators merits further attention in larger numbers of patients.

Adult↗
PubMed1996

Adherence to the Grampian joint drug formulary in general practice.

A joint drug formulary covering both hospital and general practice prescribing has been in existence in Grampian since 1990. The aims of this study were to measure adherence to this formulary in general practice and to identify who had initiated non-formulary drugs. The drug therapy of elderly patients on presentation to hospital was compared to the formulary. Of the 449 drugs prescribed 377 (84%) were recommended in the formulary. The main areas of non-formulary prescribing were antidepressants, hypnotics, nitrates and diuretics, with some non-formulary drugs being initiated by hospital prescribers. The method described was found to be extremely simple and had the advantage that it reflected actual prescribing at the time of the study.

Aged↗
PubMed1995

Sleep quality and the use of benzodiazepine hypnotics in general practice.

The aim of the study was to determine the usage patterns of benzodiazepine hypnotics, the use of other ways of improving sleep and general sleep characteristics in patients prescribed these drugs on a regular basis and in a control group of age- and sex-matched patients not receiving hypnotics. Patients receiving regular benzodiazepine hypnotic prescriptions and a control group matched for age and sex were identified from a general practice computer. They were interviewed in their own homes about their habits relating to sleep, hypnotic use and attitudes to sleep and hypnotics. None of the recommended methods of improving sleep differed significantly in frequency between the two groups or had an effect on sleep parameters. Only daytime napping was found to be slightly more frequent in hypnotic users, but had no apparent effect on self-estimates of sleep duration or latency. The hypnotic users claimed a longer sleep latency and a shorter sleep duration than non-users. More patients who took hypnotics also perceived them to be beneficial and more convenient than other ways of promoting sleep. The recommendation of sleep-promoting methods such as caffeine and alcohol avoidance and regular exercise may not be helpful in patients attempting to avoid hypnotics, as many patients already claim to use such methods.

Adult↗
PubMed1993

Nucleotide sequence analysis and heterologous expression of the Erysipelothrix rhusiopathiae dnaJ gene.

DNA sequence analysis of chromosomal DNA from the Gram-positive facultative intracellular pathogen, Erysipelothrix rhusiopathiae has identified a dnaJ heat shock gene homolog. A 1109-bp open reading frame encoding dnaJ is located immediately 3' to the E. rhusiopathiae dnaK gene. The deduced DnaJ amino acid sequence exhibits the modular structure of other members of the DnaJ protein class including a glycine-rich region and the repeating consensus sequence CXXCXGXGX. Heterologous expression of the dnaJ sequence in Escherichia coli resulted in accumulation of a unique 38.9-kDa protein with an isoelectric point of 8.0. Deletion analysis of the dnaJ gene was used to confirm that the overproduced protein was encoded by the dnaJ sequence.

Amino Acid Sequence↗
PubMed1993

Cloning, heterologous expression, and characterization of the Erysipelothrix rhusiopathiae DnaK protein.

The dnaK (hsp70) gene from the facultative intracellular pathogen Erysipelothrix rhusiopathiae was cloned by heterologous DNA hybridization of a genomic library using the Escherichia coli dnaK gene as a probe. A 3.2-kb fragment which encoded an 1,800-bp open reading frame was recovered. The deduced amino acid sequence of this open reading frame shares 56% identity with the E. coli DnaK protein. Expression of the encoded protein in E. coli by using the phage T7 promoter/polymerase system resulted in accumulation of a unique 65-kDa protein. Western blot (immunoblot) analysis of extracts from a recombinant E. coli strain using anti-E. coli DnaK polyclonal antibodies confirmed that the cloned gene encodes a DnaK homolog. The recombinant E. rhusiopathiae DnaK protein was purified to 80% homogeneity by ATP affinity chromatography. The purified material hydrolyzed ATP with a specific activity of 100 nmol min-1 mg of protein-1. Analysis of total protein extracts from E. rhusiopathiae indicates that DnaK is a highly expressed protein in this organism.

Adenosine Triphosphate↗
PubMed1993

Monoclonal antibody recognition and function of a DnaK (HSP70) epitope found in gram-negative bacteria.

The isolation and characterization of a monoclonal antibody (MAb 2G5) specific for the bacterial DnaK (HSP70) protein is described. The 2G5 MAb was initially selected because of its ability to bind to DnaK under denaturing conditions. Isotype analyses indicated that 2G5 was an immunoglobulin G2a. Dose-response Western blot (immunoblot) experiments with purified but unconcentrated 2G5 permitted detection of 10 ng of pure DnaK protein. The DnaK epitope was determined by Western blot analysis of a series of truncated DnaK fragments overproduced in Escherichia coli using 5' and 3' dnaK-deleted expression plasmids. The epitope mapped to a 22-amino-acid region spanning DnaK residues 288 and 310. Phylogenetic distribution of the epitope was examined by Western blot analysis of a wide variety of bacterial species and indicated that the epitope was uniquely present in gram-negative organisms. The proximity of the epitope to the presumed DnaK ATP-binding pocket suggested that MAb binding might inhibit DnaK ATPase activity. In vitro analysis supported this prediction and demonstrated that MAb-mediated inhibition of ATPase activity was antibody specific and occurred at stoichiometric molar ratios of MAb to DnaK. Possible mechanisms to explain the ability of the 2G5 MAb to inhibit DnaK activity are discussed.

Adenosine Triphosphatases↗
PubMed1992

Serum drug level monitoring in affective disorders.

This study surveyed serum level monitoring of lithium and carbamazepine in three psychiatric hospitals, to determine how the service is used with respect to affective disorders. The monitoring of lithium serum levels appears to be carried out in relatively close adherence to recommended guidelines. Carbamazepine serum levels are monitored with a similar frequency to lithium, despite the lack of an established therapeutic window for indications other than epilepsy. Changes in drug therapy, which are consequent upon monitoring of serum drug levels, occurred after only 7.5% of lithium and 13.7% of carbamazepine samples. Changes were made independently of serum level results with greater frequency in carbamazepine-treated patients, although less frequently with lithium-treated patients. Adverse consequences of such changes occurred only once, involving lithium. More research is needed to determine the potential benefits of carbamazepine serum level monitoring in affective disorders because the service appears to be overutilized at present.

Carbamazepine↗
PubMed1992

Rationalizing neuroleptic polypharmacy in chronic schizophrenics: effects of changing to a single depot preparation.

This study investigated the effects of transferring patients on combined depot and oral neuroleptics to a single depot preparation; a secondary objective was to assess the effects of transferring patients from one depot neuroleptic to another. It was found that, whereas transferring from one depot preparation (flupenthixol) to another (fluphenazine) had no clear disadvantage for the patients, changing over from a combined oral and depot (fluphenazine) regimen to equivalent doses of depot alone resulted in an unacceptably high rate of relapse. The reasons for this may relate to either the unique pharmacokinetics of these drugs or subtle qualitative differences between them. It is suggested that caution is necessary whenever attempts are made to rationalize polypharmacy in schizophrenic patients.

Administration, Oral↗
PubMed1992

Physiological consequences of DnaK and DnaJ overproduction in Escherichia coli.

The physiological consequences of molecular chaperone overproduction in Escherichia coli are presented. Constitutive overproduction of DnaK from a multicopy plasmid containing large chromosomal fragments spanning the dnaK region resulted in plasmid instability. Co-overproduction of DnaJ with DnaK stabilized plasmid levels. To examine the effects of altered levels of DnaK and DnaJ in a more specific manner, an inducible expression system for dnaK and dnaJ was constructed and characterized. Differential rates of DnaK synthesis were determined by quantitative Western blot (immunoblot) analysis. Moderate levels of DnaK overproduction resulted in a defect in cell septation and formation of cell filaments, but co-overproduction of DnaJ overcame this effect. Further increases in the level of DnaK terminated culture growth despite increased levels of DnaJ. DnaK overproduction was found to be bacteriocidal, and this effect was also partially suppressed by DnaJ. The bacteriocidal effect was apparent only with cultures which were allowed to enter stationary phase, indicating that DnaK toxicity is growth phase dependent.

Blotting, Western↗
PubMed1986

Determination of chlorpromazine in serum by radioreceptor assay and HPLC.

A radioreceptor assay for chlorpromazine in serum, which is based on binding to dopamine receptors, is described. This method has been postulated to measure all active metabolites as well as the parent drug. We have compared this method with an HPLC method for chlorpromazine. Dopamine-blocking activity, measured in serum samples from schizophrenic patients receiving chlorpromazine, was 1.85-9.1 times higher than serum chlorpromazine level measured by HPLC. The correlation between the two methods was 0.75. Dopamine-blocking activity was related more closely to dose of drug and to serum prolactin level than was serum chlorpromazine level measured by HPLC.

Chlorpromazine↗
PubMed1986

Radio receptor assay of serum neuroleptic levels in psychiatric patients.

The radioreceptor assay for the measurement of neuroleptic drugs in serum has been used to study the relationship between dose and serum level in schizophrenic patients receiving these drugs. The assay was found to be reproducible and capable of detecting neuroleptics in the sera of patients receiving a range of both oral and depot drugs, with the exception of trifluoperazine spansules. Linear correlations were obtained between daily dose and serum level for each drug both in individual patients on different doses and between patients on a stable dose. Extrapyramidal side effects were related to the serum neuroleptic level within, but not between, patients. The assay may be of use in clinical practice, including the assessment of compliance or poor response to neuroleptics.

Antipsychotic Agents↗
PubMed1986

Interactions between procyclidine and neuroleptic drugs. Some pharmacological and clinical aspects.

Procyclidine was administered to 25 chronic psychotic inpatients, stabilised on chlorpromazine, haloperidol or fluphenazine decanoate injection. We observed a significant reduction in mean serum levels of all three neuroleptic drugs which was reversed on stopping procyclidine and was inversely correlated with mean serum procyclidine levels. No significant alterations occurred on the BPRS scores or in serum prolactin levels throughout the study in any of the three groups. Possible mechanisms of this interaction and its clinical relevance are discussed.

Adult↗