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J K Jones

Publications and source records attributed to J K Jones.

106 records · Page 6Linked to original sources
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Pharmacogenetics and pharmacoepidemiology.

This paper seeks to stimulate consideration of the short- and long-term possibilities raised by research into pharmacogenetics and pharmacoepidemiology, to identify potential tissue databanks linked to population data, and to summarize our ethical responsibilities. Short term, we might identify selected disorders or risk factors, such as for drug-associated serious events, and might find selected target populations. Long term, we might incorporate genomics techniques into population data and map genetic risk factors for diseases and drug responses. Tissue specimens that might be linked to clinical data lie in certain data resources: clinical trials, ad hoc cohorts, case registries, and cross-sectional and longitudinal population samples. Specific areas must be addressed in research using human tissue and genetic material, including the ethical threat to privacy. We must avoid misuse of genetic information by breaching confidentiality and putting at risk specific genetically identifiable groups. The National Bioethics Advisory Commission recently addressed the issue of serum and tissue data banks in a published report summarized in this paper. Social, methodologic, and ethical issues relate to any protocol using serum and tissue, and indicate a need for broad educational efforts. We must set guidelines as pharmacogenetics research becomes a dimension of pharmacoepidemiology.

Cohort Studies↗
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Risk of selected serious cardiac events among new users of antihistamines.

This retrospective cohort study examined the risk of selected serious cardiac events in new users of either astemizole or sedating antihistamines identified from the COMPASS Ohio Medicaid population of approximately 1 million active lives per year (1986-1992). (COMPASS is an automated claims database.) There were 15,585 patients in the astemizole group and 30,105 in the sedating antihistamines group. Reports of ventricular arrhythmia or sudden death occurring within 30 days of the first antihistamine claim were identified from Medicaid claims. Medical records were obtained and reviewed by a clinician for validity of diagnoses. Records for patients without a full 30 days of follow-up were sought in the National Death Index. Death certificates were obtained for all patients who died within 30 days of the first antihistamine claim. Of 53 cases identified, 6 were in the astemizole group and 47 in the sedating antihistamines group. The relative risk for all selected cardiac events among astemizole users compared with sedating antihistamine users was 0.25 (95% confidence interval: 0.11 to 0.58), and this estimate did not change substantially when adjusted for age; sex; race; recent history of cardiovascular disease, arrhythmias, asthma/pulmonary disease, or malignant neoplasms; or concomitant prescription of other drugs. This study provided no evidence that astemizole users are at increased risk for cardiac events in the first month of use when compared with users of sedating antihistamines.

Adolescent↗
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MgATP binding changes neither the shape nor the flexibility of the heads of single myosin molecules.

The structural mechanism by which myosin heads exert force is unknown. One possibility is that the tight binding of the heads to actin drives them into a force-generating configuration. Another possibility is that the force-generating conformational change is inherent to the myosin heads. In this case the heads would make force by changing their shape according to the species of nucleotide in their active sites, the tight attachment to actin serving only to provide traction. To test this latter possibility, we used negative stain electron microscopy to search for a MgATP-induced shape change in the heads of single myosin molecules. We compared the heads of 10S smooth muscle myosin monomers (wherein MgATP is trapped at the active site) with the MgATP-free heads of 6S monomers. We found that to a resolution of about 2 nm, MgATP binding to the unrestrained myosin head does not drive it to change its shape or its flexibility. This result suggests that the head makes force by virtue of an induced fit to actin.

Adenosine Triphosphate↗
PubMedDate not supplied

Prescribing of selective serotonin reuptake inhibitors, anxiolytics, and sedative-hypnotics by general practitioners in The Netherlands: a multivariate analysis.

A study of the prescribing of anxiolytics and sedative-hypnotics and the occurrence of anxiety or sleep disorders before and after the initiation of selective serotonin reuptake inhibitor (SSRI) therapy may provide insight into differences in individual SSRIs. The purpose of our study was to evaluate whether and in what way the likelihood of being prescribed an anxiolytic or sedative-hypnotic or receiving a diagnosis of an anxiety or sleep disorder differed in patients prescribed either fluoxetine or paroxetine by a general practitioner (GP) in the Netherlands, where these two agents are the most commonly prescribed SSRIs. Episodes of SSRI treatment were constructed from a recently available GP database in the Netherlands. Logistic regression analysis was used to determine whether, after controlling for other observable factors, the receipt of paroxetine or fluoxetine was a statistically significant determinant for receipt of an anxiolytic or sedative-hypnotic or a diagnosis of an anxiety or sleep disorder. We found that patients who were prescribed fluoxetine as their index drug were less likely to receive a concomitant sedative-hypnotic on their index date compared with patients receiving paroxetine. After controlling for other observable factors, such as use of anxiolytics and sedative-hypnotics before SSRI therapy or on the index date or the existence of comorbid anxiety or sleep disorders, patients starting fluoxetine therapy were no more likely than patients starting paroxetine therapy to receive an anxiolytic or sedative-hypnotic or a diagnosis of an anxiety or sleep disorder during the 60-day post period. The likelihood of a patient's being diagnosed with or receiving a prescription for an anxiety or sleep disorder does not appear to be a differentiating factor between the prescribing of fluoxetine or paroxetine by GPs in the Netherlands.

Aged↗
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Data sources and methods for ascertaining human exposure to drugs.

Estimates of population exposure based on drug use data are critical elements in the post marketing surveillance of drugs and provide a context for assessing the various risks and benefits associated with drug treatment. Such information is important in predicting morbidity and planning public health protection strategies, indepth studies, and regulatory actions. Knowledge that a population of one thousand instead of one million may potentially be exposed to a drug can help determine how a particular regulatory problem will be handled and would obviously be a major determinant in designing a case-control or cohort study. National estimates of drug use give an overview of the most commonly used drug therapies in current practice. They also furnish valuable comparison data for specific studies of drug use limited to one group of drugs, one geographic region, or one medical care setting. The FDA has access to several different national drug use data bases, each measuring a different point in the drug distribution channels. None covers the entire spectrum of drug exposures. The major "holes" in this patchwork of data bases are the inability to measure OTC drug use with any accuracy and the lack of qualitative information on drug use in hospitals. In addition, there is no patient linkage with the data. The data can only show trends in drug use. They impart no sense of the longitudinal use of drugs for individual patients. There is no direct connection between the different data bases, all of which have their own sampling frames and their own projection methodologies. The market research companies have complete control over these methodologies and they are subject to periodic changes, a situation not entirely satisfactory for epidemiologic research. Sometimes it is a struggle to keep up with these changes. Over the past two years, every one of these data bases has undergone some type of sampling or projection methodology change. One important limitation to the use of all of these data bases is that they are subscription data bases, that is, the FDA purchases the data under contract to the marketing research companies and by doing so assumes certain contract obligations. Anytime the FDA wants to release any data outside of the Agency, it must first notify the company in sufficient time for review and approval. Subscribing to these data bases is costly, but the subscription cost is insignificant, compared to the estimated cost of duplicating these services. In spite of all of the limitations of these systems, there are obvious advantages.(ABSTRACT TRUNCATED AT 400 WORDS)

Computers↗
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International data standards for hospital-based drug surveillance.

A conference of leading pharmacoepidemiologists and experts in clinical computing has highlighted the need to support drug surveillance as an important component of automated patient care data. Citing shortcomings in existing systems, the participants made suggestions for improving the collection, storage, and compatibility of the data in hospital-based drug surveillance systems. This article describes the history and current status of this effort and may serve as a guide for others interested in international drug therapy standards.

Computer Communication Networks↗