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Biomedical subjects

James F Fries

Publications and source records attributed to James F Fries.

At least 19 recordsLinked to original sources
PubMed2006

A low tension between individual and societal time aspects in health improved outcomes.

OBJECTIVES: To review intertemporal choices, involving decisions with a trade-off between something now and something later. These choices are common in health both at an individual and societal level. METHODS: The present value of an outcome, for example, the amount of money or the health outcomes in various aspects, is equivalent to the value of a future outcome discounted with the delay of time. The concept of diminishing value over time is positive discounting. Economic forecasts generally use discount rates in which the value of a future dollar is less than the value of a present dollar, and where the discount rates are similar for the individual investor and society. The value of future health is commonly thought of as similar to the value of future money. Yet, the individual may rationally choose a discount rate that is exceedingly low or even negative. This paradox is particularly relevant when considering primary and secondary prevention, where initial and continuing costs may precede beneficent outcomes by decades, making discount rate selections the dominant factor in determining decisions. CONCLUSION: We suggest that the societal perspective should also recognize that discount rates for health outcomes are largely irrelevant and that even negative discount rates have crucial relevance.

Decision Making↗
PubMed2006

Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines.

OBJECTIVES: To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using arthritis antigen microarrays and a multiplex cytokine assay. METHODS: Serum samples from 56 patients with a diagnosis of rheumatoid arthritis of <6 months' duration were tested. Cytokine profiles were also determined in samples from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (n = 21), and from healthy individuals (n = 19). Data were analysed using Kruskal-Wallis test with Dunn's adjustment for multiple comparisons, linear correlation tests, significance analysis of microarrays (SAM) and hierarchical clustering software. RESULTS: Distinct antibody profiles were associated with subgroups of patients who exhibited high serum levels of tumour necrosis factor (TNF)alpha, interleukin (IL)1beta, IL6, IL13, IL15 and granulocyte macrophage colony-stimulating factor. Significantly increased autoantibody reactivity against citrullinated epitopes was observed in patients within the cytokine "high" subgroup. Increased levels of TNFalpha, IL1alpha, IL12p40 and IL13, and the chemokines eotaxin/CCL11, monocyte chemoattractant protein-1 and interferon-inducible protein 10, were present in early rheumatoid arthritis as compared with controls (p<0.001). Chemokines showed some of the most impressive differences. Only IL8/CXCL8 concentrations were higher in patients with PsA/ankylosing spondylitis (p = 0.02). CONCLUSIONS: Increased blood levels of proinflammatory cytokines are associated with autoantibody targeting of citrullinated antigens and surrogate markers of disease activity in patients with early rheumatoid arthritis. Proteomic analysis of serum autoantibodies, cytokines and chemokines enables stratification of patients with early rheumatoid arthritis into molecular subgroups.

Adult↗
PubMed2006

Discounting and risk characteristics in clinical decision-making.

Time-related aspects have attracted an increasing interest in medical decisions. Health promotion often works toward remote goals, and many clinical judgments and decisions include an exchange of costs today for benefits in the future. The concept of diminishing value over time is positive discounting when the benefits occur so far in the future that they seem of little value relative to the immediate cost. If there is a preference to live for the present rather than save for the future, such a preference might not contribute to good health according to a lower discount rate. As discounting is related to risk an analysis of uncertainty is required being an unavoidable condition in health work. Shared decision-making between doctor and patient has increasingly been emphasized, where risk characteristics and time-related aspects should be taken into account to reach a decision based upon mutual agreement. The framework of time and risk for analysis can perform a useful role in clinical judgments and decisions, where framing of different features of risk might diminish discounting and increase compliance to treatment. A summary of valuation factors in medical decision making is presented: (a) long-term decisions are sensitive to discount rates; (b) discount rates vary by domain, by outcome, by individuals and by level of certainty; (c) probability discounting is used if the risk is perceived as controllable; (d) the doctor uses expected value, the patient is risk aversive; (e) asymmetric discounting for patients and doctors gives poor compliance; (f) discount rates are influenced by framing.

Attitude of Health Personnel↗
PubMed2006

Midlife body mass index and hospitalization and mortality in older age.

CONTEXT: Abundant evidence links overweight and obesity with impaired health. However, controversies persist as to whether overweight and obesity have additional impact on cardiovascular outcomes independent of their strong associations with established coronary risk factors, eg, high blood pressure and high cholesterol level. OBJECTIVE: To assess the relation of midlife body mass index with morbidity and mortality outcomes in older age among individuals without and with other major risk factors at baseline. DESIGN: Chicago Heart Association Detection Project in Industry study, a prospective study with baseline (1967-1973) cardiovascular risk classified as low risk (blood pressure < or =120/< or =80 mm Hg, serum total cholesterol level <200 mg/dL [5.2 mmol/L], and not currently smoking); moderate risk (nonsmoking and systolic blood pressure 121-139 mm Hg, diastolic blood pressure 81-89 mm Hg, and/or total cholesterol level 200-239 mg/dL [5.2-6.2 mmol/L]); or having any 1, any 2, or all 3 of the following risk factors: blood pressure > or =140/90 mm Hg, total cholesterol level > or =240 mg/dL (6.2 mmol/L), and current cigarette smoking. Body mass index was classified as normal weight (18.5-24.9), overweight (25.0-29.9), or obese (> or =30). Mean follow-up was 32 years. SETTING AND PARTICIPANTS: Participants were 17,643 men and women aged 31 through 64 years, recruited from Chicago-area companies or organizations and free of coronary heart disease (CHD), diabetes, or major electrocardiographic abnormalities at baseline. MAIN OUTCOME MEASURES: Hospitalization and mortality from CHD, cardiovascular disease, or diabetes, beginning at age 65 years. RESULTS: In multivariable analyses that included adjustment for systolic blood pressure and total cholesterol level, the odds ratio (95% confidence interval) for CHD death for obese participants compared with those of normal weight in the same risk category was 1.43 (0.33-6.25) for low risk and 2.07 (1.29-3.31) for moderate risk; for CHD hospitalization, the corresponding results were 4.25 (1.57-11.5) for low risk and 2.04 (1.29-3.24) for moderate risk. Results were similar for other risk groups and for cardiovascular disease, but stronger for diabetes (eg, low risk: 11.0 [2.21-54.5] for mortality and 7.84 [3.95-15.6] for hospitalization). CONCLUSION: For individuals with no cardiovascular risk factors as well as for those with 1 or more risk factors, those who are obese in middle age have a higher risk of hospitalization and mortality from CHD, cardiovascular disease, and diabetes in older age than those who are normal weight.

Adult↗
PubMed2006

Associations of changes in exercise level with subsequent disability among seniors: a 16-year longitudinal study.

BACKGROUND: The effect of changes in physical exercise on progression of musculoskeletal disability in seniors has rarely been studied. METHODS: We studied a prospective cohort annually from 1984 to 2000 using the Health Assessment Questionnaire Disability Index (HAQ-DI). The cohort included 549 participants, 73% men, with average end-of-study age of 74 years. At baseline and at the end of the study, participants were classified as "High" or "Low" vigorous exercisers using a cut-point of 60 min/wk. Four groups were formed: "Sedentary" (Low-->Low; N = 71), "Exercise Increasers" (Low-->High; N = 27), "Exercise Decreasers" (High-->Low; N = 73), and "Exercisers" (High-->High; N = 378). The primary dependent variable was change in HAQ-DI score (scored 0-3) from 1984 to 2000. Multivariate statistical adjustments using analysis of covariance included age, gender, and changes in three risk factors, body mass index, smoking status, and number of comorbid conditions. Participants also prospectively provided reasons for exercise changes. RESULTS: At baseline, Sedentary and Increasers averaged little exercise (16 and 22 exercise min/wk), whereas Exercisers and Decreasers averaged over 10 times more (285 and 212 exercise min/wk; p <.001). All groups had low initial HAQ-DI scores, ranging from 0.03 to 0.08. Increasers and Exercisers achieved the smallest increments in HAQ-DI score (0.17 and 0.11) over 16 years, whereas Decreasers and Sedentary fared more poorly (increments 0.27 and 0.37). Changes in HAQ-DI score for Increasers compared to Sedentary were significantly more favorable (p <.05) even after multivariate statistical adjustment. CONCLUSIONS: Inactive participants who increased exercise achieved excellent end-of-study values with increments in disability similar to those participants who were more active throughout. These results suggest a beneficial effect of exercise, even when begun later in life, on postponement of disability.

Aged↗
PubMed2005

Aerobic exercise and its impact on musculoskeletal pain in older adults: a 14 year prospective, longitudinal study.

We studied the long term impact of running and other aerobic exercise on musculoskeletal pain in a cohort of healthy aging male and female seniors who had been followed for 14 years. We conducted a prospective, longitudinal study in 866 Runners' Association members (n = 492) and community controls (n = 374). Subjects were also categorized as Ever-Runners (n = 565) and Never-Runners (n = 301) to include runners who had stopped running. Pain was the primary outcome measure and was assessed in annual surveys on a double-anchored visual analogue scale (0 to 100; 0 = no pain). Baseline differences between Runners' Association members and community controls and between Ever-Runners versus Never-Runners were compared using chi-square and t-tests. Statistical adjustments for age, body mass index (BMI), gender, health behaviors, history of arthritis and comorbid conditions were performed using generalized estimating equations. Runner's Association members were younger (62 versus 65 years, p < 0.05), had a lower BMI (22.9 versus 24.2, p < 0.05), and less arthritis (35% versus 41%, p > 0.05) than community controls. Runners' Association members averaged far more exercise minutes per week (314 versus 123, p < 0.05) and miles run per week (26 versus 2, p < 0.05) and tended to report more fractures (53% versus 47%, p > 0.05) than controls. Ever-Runners were younger (62 versus 66 years, p < 0.05), had lower BMI (23.0 versus 24.3, p < 0.05), and less arthritis (35% versus 43%, p < 0.05) than Never-Runners. Ever-Runners averaged more exercise minutes per week (291 versus 120, p < 0.05) and miles run per week (23 versus 1, p < 0.05) and reported a few more fractures (52% versus 48%, p > 0.05) than Never-Runners. Exercise was associated with significantly lower pain scores over time in the Runners' Association group after adjusting for gender, baseline BMI, and study attrition (p < 0.01). Similar differences were observed for Ever-Runners versus Never-Runners. Consistent exercise patterns over the long term in physically active seniors are associated with about 25% less musculoskeletal pain than reported by more sedentary controls, either by calendar year or by cumulative area-under-the-curve pain over average ages of 62 to 76 years.

Aged↗
PubMed2005

Framing health messages based on anomalies in time preference.

Time discounting processes and their effects are increasingly taken into account in health-related decisions. Because these effects have a potentially large impact the characteristics of discounting should also be taken into consideration when framing health messages. Research on the relationship between time and health is discussed with a special focus on discounting biases. The criteria for selection of articles were potential practical application when formulating health messages. Time discounting processes vary with individuals and contexts. Therefore, no single model is expected to describe discounting processes completely. Discounting biases appear more prevalent in health decisions than in economic decisions, even when health and monetary outcomes are matched for utility. Research on decision-making under conditions of uncertainty has documented numerous anomalies of expected utility. Analysis on the anomalies related to intertemporal choice and discounted utility (DU) include the magnitude effect, dynamic inconsistency effect, instant endowment, status quo bias, and sequence effect. Discounting biases in the formulation of preventive health messages are important. The desire for behavioral change in these programs would benefit from considering the psychological factor of discounting. Framing health messages in terms of large, important outcomes or long delays should induce lower implicit discount rates. Framing health messages as losses rather than gains, or as involving a series of outcomes rather than individual outcomes, might similarly lower the implicit discount rate used.

Costs and Cost Analysis↗
PubMed2005

Cardiovascular risk profile earlier in life and Medicare costs in the last year of life.

BACKGROUND: Health care costs are generally highest in the year before death, and much attention has been directed toward reducing costs for end-of-life care. However, it is unknown whether cardiovascular risk profile earlier in life influences health care costs in the last year of life. This study addresses this question. METHODS: Prospective cohort of adults from the Chicago Heart Association Detection Project in Industry included 6582 participants (40% women), aged 33 to 64 years at baseline examination (1967-1973), who died at ages 66 to 99 years. Medicare billing records (1984-2002) were used to obtain cardiovascular disease-related and total charges (adjusted to year 2002 dollars) for inpatient and outpatient services during the last year of life. Participants were classified as having favorable levels of all major cardiovascular risk factors (low risk), that is, serum cholesterol level lower than 200 mg/dL (<5.2 mmol/L), blood pressure 120/80 mm Hg or lower and no antihypertensive medication, body mass index (calculated as weight in kilograms divided by the square of height in meters) lower than 25, no current smoking, no diabetes, and no electrocardiographic abnormalities, or unfavorable levels of any 1 only, any 2 only, any 3 only, or 4 or more of these risk factors. RESULTS: In the last year of life, average Medicare charges were lowest for low-risk persons. For example, cardiovascular disease-related and total charges were lower by 10,367 dollars and 15,318 dollars compared with those with 4 or more unfavorable risk factors; the fewer the unfavorable risk factors, the lower the Medicare charges (P for trends <.001). Analyses by sex showed similar patterns. CONCLUSION: Favorable cardiovascular risk profile earlier in life is associated with lower Medicare charges at the end of life.

Adult↗
PubMed2005

Antigen microarray profiling of autoantibodies in rheumatoid arthritis.

OBJECTIVE: Because rheumatoid arthritis (RA) is a heterogeneous autoimmune disease in terms of disease manifestations, clinical outcomes, and therapeutic responses, we developed and applied a novel antigen microarray technology to identify distinct serum antibody profiles in patients with RA. METHODS: Synovial proteome microarrays, containing 225 peptides and proteins that represent candidate and control antigens, were developed. These arrays were used to profile autoantibodies in randomly selected sera from 2 different cohorts of patients: the Stanford Arthritis Center inception cohort, comprising 18 patients with established RA and 38 controls, and the Arthritis, Rheumatism, and Aging Medical Information System cohort, comprising 58 patients with a clinical diagnosis of RA of <6 months duration. Data were analyzed using the significance analysis of microarrays algorithm, the prediction analysis of microarrays algorithm, and Cluster software. RESULTS: Antigen microarrays demonstrated that autoreactive B cell responses targeting citrullinated epitopes were present in a subset of patients with early RA with features predictive of the development of severe RA. In contrast, autoimmune targeting of the native epitopes contained on synovial arrays, including several human cartilage gp39 peptides and type II collagen, were associated with features predictive of less severe RA. CONCLUSION: Proteomic analysis of autoantibody reactivities provides diagnostic information and allows stratification of patients with early RA into clinically relevant disease subsets.

Algorithms↗
PubMed2005

Frailty, heart disease, and stroke: the Compression of Morbidity paradigm.

Frailty, the loss of physiologic organ reserve with age, and chronic illness, such as heart disease and stroke, which may accelerate the development of frailty, become the dominant determinants of ill-health in those who escape the hazards of early and mid-life. The Compression of Morbidity paradigm holds that if the average age at first chronic infirmity is postponed, and if this postponement is greater than increases in life expectancy, then average cumulative lifetime morbidity will decrease, squeezed between a later onset and the time of death. The National Long-Term Care Survey, National Health Interview Survey, and other data document declining U.S. disability trends since 1982; accelerating recently, at about 2% per year. The decline in mortality is only 1% a year, documenting Compression of Morbidity in the U.S. population. Frailty, increasing exponentially because of linear declines in multiple organ systems, mandates converging morbidity and mortality rates as longevity increases. Longitudinal studies now link good health risk status with reduced lifetime disability; those with few health risks have only one-fourth the disability of those who have more risks, and the onset of disability is postponed from 7 to 12 years. Randomized controlled trials of senior health enhancement programs have shown reduction in health risks, improved health status, and decreased medical costs. Current health enhancement opportunities can increase health gains for seniors under the umbrella paradigm of the Compression of Morbidity. Effective interventions to prevent or postpone heart disease and stroke will decrease lifetime morbidity.

Aged↗
PubMed2005

Challenges and progress in adverse event ascertainment and reporting in clinical trials.

Toxicity, safety, and tolerability are integral facets of patient risk/benefit decisions, yet the capacity to define, measure, and compare these aspects is underdeveloped compared to aspects of efficacy. There are many reasons for this, scientific and administrative, but all are surmountable. Probably the greatest primary obstacle is the absence of a measurement instrument designed specifically for this purpose. There are increasing calls from various stakeholders for better evidence, and therefore better ascertainment, in this area, especially in randomized trials, and for these reasons OMERACT began deliberations about these concepts in 1994. A prototype coding instrument (the Rheumatology Common Toxicity Criteria) was developed and discussed at OMERACT 5. In the 2 years before OMERACT 7, a process of concept development and iterative design and testing were conducted to develop a patient self-report and investigator-reported adverse event instruments designed for use in trials at the time of visit. The predominant workload is performed by the patient in a self-report checklist, which is then mapped by the trialist onto a medically sophisticated version. This article presents background on the process of developing a dual adverse event instrument, which was presented and critically discussed in detail at OMERACT 7.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Standardized assessment of adverse events in rheumatology clinical trials: summary of the OMERACT 7 drug safety module update.

A presentation, demonstration, and discussion of recently developed adverse event instruments were the topics for the OMERACT 7 Drug Safety Module. The module began with a plenary introducing the needs and challenges of adverse event ascertainment. It was followed by a review of module work from previous OMERACT meetings on a prototype coding instrument (Rheumatology Common Toxicity Criteria), then a brief description of the process behind the recently developed patient self-report and investigator report adverse event instruments. These current instruments are designed for use in controlled trials although they could be used in other settings. The instruments rely primarily on patient self-reporting using a checklist, which the investigator then folds into a parallel structured but more medically sophisticated instrument. In pilot testing, this innovative dual-use system has shown reliability and acceptability, while preserving validity. A "stakeholder panel" of representatives from 8 sectors followed--patient, nurse investigator, regulator, clinician scientist, industry, OMERACT, global public health/WHO, and Cochrane Collaboration--for their perspectives on the needs, challenges, and potential ways forward for adverse event ascertainment and reporting in clinical trials. At the breakout session small focus groups participated in hands-on interactive testing of one of 3 versions of the instruments, which differ in degree of comprehensiveness. Each focus group had a participatory patient with rheumatoid arthritis. At a second plenary there was group feedback by rapporteurs and presentation of results from pilot studies of iterative testing of validity, reliability, and feasibility of the instruments. During plenary discussion a frequent suggestion for improvement was to refine the process so that event ascertainment could be done entirely using the patient instrument with minimal input from the investigator at the visit, if patient-investigator agreement was high. Most found the patient checklist attractive, particularly if the patient instrument was shown to be reliable and valid. Finally, a future research agenda was discussed.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

Percentile benchmarks in patients with rheumatoid arthritis: Health Assessment Questionnaire as a quality indicator (QI).

Physicians are in need of a simple objective, standardized tool to compare their patients with rheumatoid arthritis, as a group and individually, with national standards. The Disability Index of the Health Assessment Questionnaire (HAQ-DI) is a simple, robust tool that can fulfill these needs. However, use of this tool as a quality indicator (QI) is hampered by the unavailability of national reference values or benchmarks based on large, multicentric, heterogenous longitudinal patient cohorts. We utilized the 20-year longitudinal prospective data from 11 data banks of Arthritis Rheumatism and Aging Medical Information to calculate reference values for HAQ-DI. Overall, 6436 patients with rheumatoid arthritis were longitudinally followed for 32,324 person-years over the 20 years from 1981 to 2000. There were 64,647 HAQ-DI measurements, with an average of 19 measurements per person. Overall, 75% of patients were women and 89% were Caucasian; the median baseline age was 58.4 years and the median baseline HAQ-DI was 1.13. Few patients were treated with biologics. The HAQ-DI values had a Gaussian distribution except for the approximately 10% of observations showing no disability. Percentile benchmarks allow disability outcomes to be compared and contrasted between different patient populations. Reference values for the HAQ-DI, presented here numerically and graphically, can be used in clinical practice as a QI measure to track functional disability outcomes and to measure response to therapy, and by arthritis patients in self-management programs.

Antirheumatic Agents↗
PubMed2004

Equipoise, design bias, and randomized controlled trials: the elusive ethics of new drug development.

The concept of 'equipoise', or the 'uncertainty principle', has been represented as a central ethical principle, and holds that a subject may be enrolled in a randomized controlled trial (RCT) only if there is true uncertainty about which of the trial arms is most likely to benefit the patient. We sought to estimate the frequency with which equipoise conditions were met in industry-sponsored RCTs in rheumatology, to explore the reasons for any deviations from equipoise, to examine the concept of 'design bias', and to consider alternative ethical formulations that might improve subject safety and autonomy. We studied abstracts accepted for the 2001 American College of Rheumatology meetings that reported RCTs, acknowledged industry sponsorship, and had clinical end-points (n = 45), and examined the proportion of studies that favored the registration or marketing of the sponsor's drug. In every trial (45/45) results were favorable to the sponsor, indicating that results could have been predicted in advance solely by knowledge of sponsorship (P < 0.0001). Equipoise clearly was being systematically violated. Publication bias appeared to be an incomplete explanation for this dramatic result; this bias occurs after a study is completed. Rather, we hypothesize that 'design bias', in which extensive preliminary data are used to design studies with a high likelihood of being positive, is the major cause of the asymmetric results. Design 'bias' occurs before the trial is begun and is inconsistent with the equipoise principle. However, design bias increases scientific efficiency, decreases drug development costs, and limits the number of subjects required, probably reducing aggregate risks to participants. Conceptual and ethical issues were found with the equipoise principle, which encourages performance of negative studies; ignores patient values, patient autonomy, and social benefits; is applied at a conceptually inappropriate decision point (after randomization rather than before); and is in conflict with the Belmont, Nuremberg, and other sets of ethical principles, as well as with US Food and Drug Administration procedures. We propose a principle of 'positive expected outcomes', which informs the assessment that a trial is ethical, together with a restatement of the priority of personal autonomy.

Bias↗
PubMed2004

Measuring effectiveness of drugs in observational databanks: promises and perils.

Observational databanks have inherent strengths and shortcomings. As in randomized controlled trials, poor design of these databanks can either exaggerate or reduce estimates of drug effectiveness and can limit generalizability. This commentary highlights selected aspects of study design, data collection and statistical analysis that can help overcome many of these inadequacies. An international metaRegister and a formal mechanism for standardizing and sharing drug data could help improve the utility of databanks. Medical journals have a vital role in enforcing a quality checklist that improves reporting.

Antirheumatic Agents↗