Panel: The Interplay of Economic and Clinical Issues

Dr. Jones is a clinical pharmacologist/pharmacoepidemiologist trained in geriatrics and internal medicine with a longstanding interest in the study of adverse drug reactions, drug utilization, and drug development and regulation. She received her medical training at Baylor College of Medicine, followed by clinical training in internal medicine, a fellowship in clinical pharmacology, and a PhD in developmental pharmacology at University of California, San Francisco. Interested in the translation of basic pharmacology information to the practice site, she practiced, taught clinical pharmacology, and carried out early research in drug utilization at Pacific Medical Center in San Francisco until 1978, when she came to Washington, DC as Director of the FDA\u27s Division of Drug Experience (now the Office of Drug Safety) until 1984. Leaving the FDA, she returned to practice medicine and geriatrics at Georgetown University, where she continues as Adjunct Clinical Professor of Pharmacology. She also holds Adjunct Professor appointments at George Washington University School of Public Health, and the University of Michigan School of Public Health Summer Epidemiology program where she teaches a one-week course in pharmacoepidemiology. She has also served as a PhD Examiner at the Karolinska Institute, and as a member of several NIH and AHRQ Study Sections. In 1988, she began a consulting business, The Degge Group, Ltd. (Degge). The mission of The Degge Group, Ltd. is to optimize the therapy and prevention of disease in populations in the U.S. and abroad through regulatory support, innovative epidemiological research, education, and product development. In pursuit of this mission, Degge works on behalf of pharmaceutical and consumer healthcare company clients, healthcare systems, and government agencies. Degge provides timely and novel solutions to safety issues from regulatory, scientific, and public health perspectives. Dr. Jones also serves as President of the Pharmaceutical Education and Research Institute (PERI) a non-profit organization that provides a range of educational courses on drug development. Throughout her career, Dr. Jones has been dedicated to international cooperation and communication in the field of drug safety. Beginning in 1978, while at FDA, Dr. Jones represented the FDA to the World Health Organization (WHO) Collaborating Center for International Drug Monitoring in Uppsala, Sweden, serving as Chair from 1981-85. She has served on the International Society for Pharmacoepidemiology Board since 1989, including terms as President and VP Finance. In 1990, she helped found and served on the Executive Committee of The International Medical Benefit Risk Foundation - RAD-AR, Geneva, Switzerland. Dr. Jones has chaired the Committee on Drug Utilization for the U.S. Pharmacopoeia (USP) in the early 1990’s, and is a member the Council for International Organizations of Medical Sciences (CIOMS) Standardized Medical Query (SMQ) Working Group since 2004. She has represented international pharmaceutical companies before U.S., European and other international regulatory bodies on drug development, safety and risk management issues. Dr. Jones has published numerous articles relating to adverse reactions, post marketing surveillance of drugs, pharmacoepidemiology and natural history of disease, drugs in populations (i.e., geriatric, pediatric patients) and drug information for patients and physicians

Persuasive Normative Messages: The Influence of Injunctive and Personal Norms on Using Free Plastic Bags

In this exploratory field-study, we examined how normative messages (i.e., activating an injunctive norm, personal norm, or both) could encourage shoppers to use fewer free plastic bags for their shopping in addition to the supermarket’s standard environmental message aimed at reducing plastic bags. In a one-way subjects-design (N = 200) at a local supermarket, we showed that shoppers used significantly fewer free plastic bags in the injunctive, personal and combined normative message condition than in the condition where only an environmental message was present. The combined normative message did result in the smallest uptake of free plastic bags compared to the injunctive and personal normative-only message, although these differences were not significant. Our findings imply that re-wording the supermarket’s environmental message by including normative information could be a promising way to reduce the use of free plastic bags, which will ultimately benefit the environmen

THE ECONOMIC AND FISCAL IMPACTS OF A CHEESE PLANT AND DAIRIES IN THE PANHANDLE OF TEXAS

Agribusiness,

Elevated ethyl methanesulfonate (EMS) in nelfinavir mesylate (Viracept®, Roche): overview

Roche's protease inhibitor nelfinavir mesylate (Viracept®) produced between March 2007-June 2007 was found to contain elevated levels of ethyl methanesulfonate (EMS), a known mutagen (alkylator) – leading to a global recall of the drug. EMS levels in a daily dose (2,500 mg Viracept/day) were predicted not to exceed a dose of ~2.75 mg/day (~0.055 mg/kg/day based on 50 kg patient). As existing toxicology data on EMS did not permit an adequate patient risk assessment, a comprehensive animal toxicology evaluation of EMS was conducted. General toxicity of EMS was investigated in rats over 28 days. Two studies for DNA damage were performed in mice; chromosomal damage was assessed using a micronucleus assay and gene mutations were detected using the MutaMouse transgenic model. In addition, experiments designed to extrapolate animal exposure to humans were undertaken. A general toxicity study showed that the toxicity of EMS occurred only at doses ≥ 60 mg/kg/day, which is far above that received by patients. Studies for chromosomal damage and mutations in mice demonstrated a clear threshold effect with EMS at 25 mg/kg/day, under chronic dosing conditions. Exposure analysis (Cmax) demonstrated that ~370-fold higher levels of EMS than that ingested by patients, are needed to saturate known, highly conserved, error-free, mammalian DNA repair mechanisms for alkylation. In summary, animal studies suggested that patients who took nelfinavir mesylate with elevated levels of EMS are at no increased risk for carcinogenicity or teratogenicity over their background risk, since mutations are prerequisites for such downstream events. These findings are potentially relevant to >40 marketed drugs that are mesylate salts

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134867/1/ajad12459.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134867/2/ajad12459_am.pd

“We can all just get on a bus and go” : Rethinking independent mobility in the context of the universal provision of free bus travel to young Londoners

This paper uses qualitative data from interviews with 118 young Londoners (age 12-18) to examine how the universal provision of free bus travel has affected young people’s independent mobility. Drawing on Sen’s ‘capabilities approach’, we argue that free bus travel enhanced young Londoners’ capability to shape their daily mobility, both directly by increasing financial access and indirectly by facilitating the acquisition of the necessary skills, travelling companions and confidence. These capabilities in turn extended both opportunity freedoms (e.g. facilitating non-“necessary” recreational and social trips) and process freedoms (e.g. feeling more independent by decreasing reliance on parents). Moreover, the universal nature of the entitlement rendered buses a socially inclusive way for groups to travel and spend time together, thereby enhancing group-level capabilities. We believe this attention to individual and group capabilities for self-determination provides the basis for a broader and more child-centred view of ‘independent mobility’ than the typical research focus upon ‘travelling without an adult’ and acquiring parental permissions.Peer reviewe

Imaging Alzheimer's genetic risk using Diffusion MRI: a systematic review

Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to investigate changes in white matter microstructure in Alzheimer’s Disease. This paper aims to systematically review studies that examined the effect of Alzheimer’s risk genes on white matter microstructure. We assimilated findings from 37 studies and reviewed their diffusion pre-processing and analysis methods. Most studies estimate the diffusion tensor (DT) and compare derived quantitative measures such as fractional anisotropy and mean diffusivity between groups. Those with increased AD genetic risk are associated with reduced anisotropy and increased diffusivity across the brain, most notably the temporal and frontal lobes, cingulum and corpus callosum. Structural abnormalities are most evident amongst those with established Alzheimer’s Disease. Recent studies employ signal representations and analysis frameworks beyond DT MRI but show that dMRI overall lacks specificity to disease pathology. However, as the field advances, these techniques may prove useful in pre-symptomatic diagnosis or staging of Alzheimer’s disease

General practitioners' views on reattribution for patients with medically unexplained symptoms: a questionnaire and qualitative study

Background: The successful introduction of new methods for managing medically unexplained symptoms in primary care is dependent to a large degree on the attitudes, experiences and expectations of practitioners. As part of an exploratory randomised controlled trial of reattribution training, we sought the views of participating practitioners on patients with medically unexplained symptoms, and on the value of and barriers to the implementation of reattribution in practice. Methods: A nested attitudinal survey and qualitative study in sixteen primary care teams in north-west England. All practitioners participating in the trial (n = 74) were invited to complete a structured survey. Semi-structured interviews were undertaken with a purposive sub-sample of survey respondents, using a structured topic guide. Interview transcripts were used to identify key issues, concepts and themes, which were grouped to construct a conceptual framework: this framework was applied systematically to the data. Results: Seventy (95%) of study participants responded to the survey. Survey respondents often found it stressful to work with patients with medically unexplained symptoms, though those who had received reattribution training were more optimistic about their ability to help them. Interview participants trained in reattribution (n = 12) reported that reattribution increased their confidence to practice in a difficult area, with heightened awareness, altered perceptions of these patients, improved opportunities for team-building and transferable skills. However general practitioners also reported potential barriers to the implementation of reattribution in routine clinical practice, at the level of the patient, the doctor, the consultation, diagnosis and the healthcare context. Conclusion: Reattribution training increases practitioners' sense of competence in managing patients with medically unexplained symptoms. However, barriers to its implementation are considerable, and frequently lie outside the control of a group of practitioners generally sympathetic to patients with medically unexplained symptoms and the purpose of reattribution. These findings add further to the evidence of the difficulty of implementing reattribution in routine general practice