Natural levels of abnormalities in the trilling frog (Neobactrachus centralis) at the Olympic Dam mine.
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Abnormalities, Radiation-Induced↗
Biomedical subjects
J L Read
Publications and source records attributed to J L Read.
Health care innovation: progress report and focus on biotechnology.
Funding for biomedical research has shifted from government to the private sector. One reason is rapid expansion in the number and strength of U.S. biotechnology companies, which collectively spend more than $6 billion a year on biomedical research. Most of these companies are not yet profitable and therefore depend on flows of capital from private investors, Wall Street, and large pharmaceutical company collaborations. Investment in the new drugs, devices, and vaccines in this pipeline is sensitive to signals emanating from the debate on health care reform, suggesting that new federal policy will have a major impact on steering the type of innovation to emerge in the future.
Biotechnology↗
Light-directed, spatially addressable parallel chemical synthesis.
Solid-phase chemistry, photolabile protecting groups, and photolithography have been combined to achieve light-directed, spatially addressable parallel chemical synthesis to yield a highly diverse set of chemical products. Binary masking, one of many possible combinatorial synthesis strategies, yields 2n compounds in n chemical steps. An array of 1024 peptides was synthesized in ten steps, and its interaction with a monoclonal antibody was assayed by epifluorescence microscopy. High-density arrays formed by light-directed synthesis are potentially rich sources of chemical diversity for discovering new ligands that bind to biological receptors and for elucidating principles governing molecular interactions. The generality of this approach is illustrated by the light-directed synthesis of a dinucleotide. Spatially directed synthesis of complex compounds could also be used for microfabrication of devices.
Amino Acid Sequence↗
Health care innovation: a progress report.
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Communication↗
The cost effectiveness of auranofin: results of a randomized clinical trial.
In a 6-month randomized trial at 14 sites, the cost effectiveness of auranofin (AF) treatment for patients with rheumatoid arthritis was gauged in comparison with placebo. Measures of global health and of impacts on daily life suggest that the benefits of disease modification outweigh adverse effects after 4 and 6 months of treatment (p less than 0.01), with negligible differences between placebo and treated patients after 1 and 2 months. Additional medical costs directly associated with AF treatment amounted to $778/patient annually. Observed differences in less direct medical costs, help received, and earnings were not statistically significant.
Adult↗
Measuring overall health: an evaluation of three important approaches.
There is growing recognition that meaningful measures of health-related quality of life must be used to evaluate health care interventions. We examined the practicality and validity of three promising measures of overall health: the General Health Rating Index (GHRI), the Quality of Well-being Scale (QWB), and the Sickness Impact Profile (SIP). Practicality was assessed in terms of interviewer training required, administration time, and respondent burden. Content validity, convergent construct validity, and tests of discriminant validity were also evaluated. Although differing in theory and application, we found that each instrument performed according to the claims of the developers and could provide useful, valid data on overall health. The GHRI may be preferred where brief, self-administered forms are required; the QWB has advantages when health assessments are used to calculate cost-effectiveness; and the SIP is a versatile, easy to understand measure dealing with a wide range of specific dysfunctions. It is worth the required effort to include well-studied measures such as these in any trial intended to provide definitive information on the effectiveness of health care interventions.
Activities of Daily Living↗
The relation of body weight to length of stay and charges for hospital services for patients undergoing elective surgery: a study of two procedures.
We studied the relation of body weight to lengths of stay and total charges for all patients hospitalized at the Brigham and Women's Hospital for total knee replacement and total hip replacement during a 12-month period. Patients with moderate obesity (actual body weight 141-170 per cent of ideal) had lengths of stay and total charges similar to normal weight patients (body weight 100-110 per cent ideal). However, patients who were extremely overweight (body weight greater than or equal to 188 per cent ideal) had mean lengths of stay 35 per cent longer (28.9 days vs 21.5) and total charges 30 per cent higher ($25,692 vs $19,576) than patients with normal weight. Those who were extremely underweight (body weight less than or equal to 75 per cent ideal) had mean lengths of stay 40 per cent longer (30.1 days vs 21.5) and total charges 35 per cent higher ($26,447 vs $19,576).
Aged↗
Application of decision analysis to drug selection for formulary addition.
Decision analysis (DA) is a quantitative method for making decisions, incorporating both probabilistic data and value judgments, and clinical and economic outcomes. The P & T Committee at the Mary Hitchcock Memorial Hospital used this technique to aid in selection of a third-generation cephalosporin for formulary addition. Cost-specific data from this hospital, together with clinical data derived from the medical literature, and a panel of infectious disease specialists were used to compare costs associated with antibiotic regimens of three infections. Results show that ceftizoxime is the least costly treatment for hospital-acquired pneumonia and sepsis of unknown origin, whereas metronidazole plus gentamicin is the least costly regimen for intra-abdominal infections. This demonstrates that drugs with higher acquisition costs can, in some cases, be less expensive than drugs with lower acquisition costs when the total cost of drug therapy is considered.
Cephalosporins↗
Auranofin therapy and quality of life in patients with rheumatoid arthritis. Results of a multicenter trial.
In a six-month, randomized, double-blind study at 14 centers, auranofin (3 mg twice daily) was compared with placebo in the treatment of patients with classic or definite rheumatoid arthritis. All patients had unremitting disease for at least the previous six months and at least three months of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, oral steroids, and analgesics were allowed throughout the trial. Efficacy was analyzed in 154 patients who received auranofin and 149 who received placebo. To reflect an expanded view of outcome assessment, the measures used included some 20 nontraditional measures of functional performance, pain, global impression, and utility (worth or value) in addition to five standard clinical measures of rheumatoid synovitis (e.g., number of tender joints). The nontraditional measures were mainly in the form of structured questionnaires administered by trained interviewers. To minimize the statistical problem of multiple comparisons, most of the measures were grouped into four composites--clinical (standard measures), functional, global, and pain--and the treatment effect for each composite was tested at the 0.0125 level of significance. Auranofin was superior to placebo in the clinical (p = 0.003), functional (p = 0.001), and global (p = 0.007) composites and trended similarly in the pain composite (p = 0.021). Individual measures within the composites consistently favored auranofin. Other measures, not part of the composites, also favored auranofin, including a patient utility measure designed for this study, the PUMS (p = 0.002). Results confirm the hypothesis that the favorable effect of auranofin on clinical synovitis is accompanied by improvements across a range of outcomes relevant to the patient's quality of life.
Adult↗
Multidisciplinary treatment of obesity with a protein-sparing modified fast: results in 668 outpatients.
Six hundred sixty-eight obese outpatients, 71 per cent (+/- 34) in excess of ideal weight, were enrolled in a multidisciplinary weight control program. The major components of the program included nutrition, education, behavior modification, and exercise. Rapid weight loss was accomplished using a very low calorie (less than 800 kcal) ketogenic diet. Patients adhered to the protein sparing modified fast (PSMF) for 17 +/- 12 weeks and averaged 9 +/- 17 weeks in a refeeding/maintenance program. Mean weight loss was 47 +/- 29 lb (21 +/- 13 kg) at the point of minimum weight and 41 +/- 29 lb (19 +/- 13 kg) at the end of the maintenance period. Systolic and diastolic blood pressure and serum triglycerides fell significantly in men and women. Success in weight loss was greatest in the heaviest patients, those who adhered the longest to the PSMF, and those who stayed the longest in the maintenance program.
Adult↗
Aspirin and its expensive substitutes: prescribing patterns and cost implications.
Relatively expensive nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed products, although many rheumatologists continue to recommend aspirin as the initial drug of choice for a variety of musculoskeletal problems. We reviewed 100 charts of patients given NSAIDs in a VA clinic to see how many had relative contraindications for aspirin, such as previous salicylate intolerance, peptic ulcer disease, gastrointestinal bleeding, or failure to respond to aspirin. Only 28% of patients on the expensive preparations had any of these problems noted in their charts. With an average retail cost difference of $14 to $29 per month, large potential savings exist for those who purchase anti-inflammatory products, if physicians would initially prescribe aspirin for appropriate patients.
Anti-Inflammatory Agents↗
Physician beliefs, attitudes, and prescribing behavior for anti-inflammatory drugs.
Psychologists have distinguished between "beliefs" and "attitudes" to help explain human behavior. To investigate the relationship between physician beliefs, attitudes, and their prescribing behavior for anti-inflammatory medication, 30 doctors in two Veterans Administration clinics were surveyed by questionnaire, and 1,265 of their prescriptions were collected. Their estimates of drug costs and the percent of patients who would have response to therapy or side effects were considered "beliefs." The "attitudes" measured were the relative importance physicians placed on six factors when choosing therapy: effectiveness, side effects, likelihood of compliance, placebo effect, cost, and the patient's perception of the physician. Physicians believed that efficacy of the different proprietary nonsteroidal anti-inflammatory agents and aspirin compounds was comparable. They perceived indomethacin as more toxic than other nonsteroidal anti-inflammatory drugs (p less than 0.01), and enteric-coated aspirin as less toxic than plain aspirin (p less than 0.01). Physicians wrote 5.7 times as many prescriptions for proprietary nonsteroidal anti-inflammatory agents as for aspirin compounds. A correlation was not observed between relative use of proprietary agents versus aspirin compounds and beliefs about costs, response rates, or side effects rates; however, attitudes regarding the importance of cost and placebo effects were correlated with prescribing behavior (p less than 0.05).
Anti-Inflammatory Agents↗
Feasibility of willingness-to-pay measurement in chronic arthritis.
Quantification of nonmonetary aspects of disease is a major challenge for economic analysts. Using the amounts of money recipients are willing to pay for nonmonetary benefits has theoretical appeal, but it has proven difficult to implement. Difficulties encountered include noncomprehension by subjects, misrepresentation of preferences, extraneous determinants of answers, and ethical concerns. In a preliminary exploration of feasibility, 184 patients with osteoarthritis and rheumatoid arthritis were asked their willingness to pay (WTP) for hypothetical complete cure. With minimal pressure put on the patients to respond, 27 percent gave plausible answers. People with more schooling, with paid employment, or who were having more treatments for their arthritis were more likely to respond. Patients were willing on average to pay 17 percent of family income for arthritis cure. Methods for measuring WTP are being strengthened and may soon play an important role in health services research.
Arthritis↗
Preferences for health outcomes. Comparison of assessment methods.
This study compared standard gamble (SG), time trade-off (TTO), and category scaling (CS) methods for assessing preferences among hypothetical outcomes of coronary artery bypass surgery. High correlations among assessment methods, as found in some previous studies, do not assure the absence of systematic differences in rating obtained by different methods. This study used analysis of variance to test for differences among the three assessment methods. Questionnaire responses were obtained from 67 of 109 physicians participating in a postgraduate course on clinical decision making, following a lecture and workshop on utility theory. SG and CS were used to rate multivariate combinations of angina (none, moderate, and severe) and survival (0, 5, and 10 years); and SG, TTO, and CS were used to rate univariate outcomes with angina (none, moderate, and severe) for the remainder of their life expectancy. SG ratings were higher than TTO ratings, which were higher than CS ratings (p less than 0.001 for all comparisons). Multivariate responses revealed a significant interaction between angina and survival dimensions using CS, but not using SG. We conclude that these methods are not interchangeable and that differences between SG and CS require a more complex explanation than differences in attitude toward risk.
Angina Pectoris↗
Benefits of reducing--revisited.
The major premise by which weight reduction is used as a medical therapy is the fact that obesity is a primary risk factor in the onset and severity of many medical diseases. Hypertension, coronary artery disease, adult onset diabetes mellitus, complications of major abdominal and thoracic surgery, cancer of the breast and colon, and degenerative joint disease are prevalent diagnoses. The data to support weight reduction use as a medical therapy derive primarily from studies of cardiovascular disease. These studies show lowering of blood pressure and reduction of risk factors for glucose intolerance, angina, and hyperlipidaemia. The magnitude of weight loss (percent reduction in excess body weight) is important; 10 per cent reduction is a firm threshold in obese patients (greater than 130%- less than 200% ideal body weight). Success at achieving this medical therapy is most frequent using very low calorie diets which average 30-40% reduction of excess body weight. Mild and moderate hypertension will respond in 90% of patients. Type II diabetes mellitus patients can become free of exogenous insulin requirement. Response to general anaesthesia and control of respiratory distress syndrome will improve if preoperative weight loss is achieved. Improved cardiovascular fitness and relief of exertional dyspnoea are other clinically important outcomes of very low calorie diet therapy. A high priority exists to investigate the use of comprehensive professional weight control therapy as medical treatment.
Body Weight↗
Variation in antenatal testing over time and between clinic settings.
Variation in the use of diagnostic procedures may be due to characteristics of patients, physicians, or their environment. Testing rates for 24-hour urinary estriol levels (EST), diagnostic ultrasound, and antepartum fetal heart rate testing (AFHRT) were examined in 8,527 deliveries from 1975 through 1978. Over the period, utilization of EST remained constant at about 7% of deliveries, while ultrasound increased from 20% to 35% and AFHRT, from 7% to 12%. This increase persisted after stratifying patients on a multivariate confounder score using 45 items of clinical information. Those receiving antenatal care in a hospital-based group practice or a resident-staffed community clinic were more likely to be tested than patients seen in private offices or a prepaid group practice.
Adolescent↗
Cost-effective choice of antimicrobial therapy for serious infections.
The authors evaluated the financial and health implications of treatment choices for three serious classes of infection: hospital-acquired pneumonia, intra-abdominal infection, and sepsis of unknown origin. Data were obtained from a systematic review of clinical literature and published data bases, by written questionnaire from a panel of infectious disease authorities, and from actual costs at a tertiary-care hospital. For pneumonia and sepsis, the third-generation cephalosporin evaluated (ceftizoxime) was found to be less expensive than other regimens, when costs of dose preparation and administration, monitoring, and toxicity were added to drug acquisition costs. The lowest-cost regimen for intra-abdominal infection was metronidazole plus gentamicin. Modest differences in efficacy would easily outweigh differences in toxicity, however, and could justify the use of more expensive regimens (e.g., mezlocillin plus gentamicin for hospital-acquired pneumonia, and cefoxitin plus gentamicin for intra-abdominal infection). If all regimens are assumed to be equally efficacious, then the third-generation cephalosporin was both lowest in cost and, owing to its low toxicity, greatest in net health benefit.
Abdomen↗
Is upper gastrointestinal radiography necessary in the initial management of uncomplicated dyspepsia? A randomized controlled trial comparing empiric antacid therapy plus patient reassurance with traditional care.
STUDY OBJECTIVE: To compare two strategies for the evaluation and management of patients who have had acute dyspepsia for four days or more: empiric high-dose antacid therapy combined with patient reassurance (empiric care) versus therapy based on prompt upper gastrointestinal radiography (traditional care). DESIGN: Prospective, randomized trial. The patients in the empiric care group were reassured that upper gastrointestinal radiography was not necessary and were subsequently treated with high-dose empiric antacid therapy (15-30 ml of high-potency antacid one and three hours after meals and at bedtime). The traditional care group after meals and at bedtime). The traditional care group received upper gastrointestinal radiography as part of the initial evaluation. Subsequent treatment was determined by individual physicians based on test results. SETTINGS: Fee-for-service, hospital-based primary care practice and Veteran's Administration medical center outpatient clinic. PATIENTS: All patients were less than 70 years of age and without gastrointestinal bleeding, anemia, significant weight loss, or other specified symptoms of severe acid peptic disease. Fifty patients were randomized to traditional care, and 51 to empiric care. Pre-randomization clinical features were identical with the exception of sex distribution and baseline disability. MEASUREMENTS AND MAIN RESULTS: After six months of follow-up, there were no significant differences in symptom scores, disability, satisfaction, and quality of life measures (as measured by the Sickness Impact Profile scores) between the two groups. Findings were unchanged when adjusted for sex, study site, alcohol consumption, and cigarette smoking. Of the radiographs obtained in the traditional care group, 13 (27%) showed duodenal ulcer disease, gastritis, or duodenitis. There were no serious complications of ulcer disease or therapy noted in either group. The average costs per patient associated with traditional care at one study site were greater, $286 versus $116 (p less than 0.0001). CONCLUSIONS: Select patients with dyspepsia receiving a combination of reassurance and empiric antacid therapy do as well as patients whose initial management strategy includes upper gastrointestinal radiography, at a substantially lower cost.
Adult↗