Negative financial incentives and ERISA's fiduciary obligations: a route around preemption?
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Biomedical subjects
Publications and source records attributed to P Miller.
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NORA is an observational registry of postmenopausal US women with periodic collection of event and treatment data that will create a database including several hundred thousand subjects. It will utilize peripheral and central measurements of bone density and relate these to other risk factors, treatment patterns, and the natural history of osteoporosis. Initiated in the fall of 1997, the registry will be open to women throughout the United States who agree to complete baseline and on-going surveys. The database created by NORA will provide a resource that is unmatched in size and scope in the medical field and will allow for future research in a number of areas including patient outcomes, types of follow-up employed in clinical practice, diagnostic cost modelling, and osteoporosis therapy use (type, patient compliance, persistence and satisfaction). In addition, upon approval by the Steering Committee, women enrolled in the registry may be randomly selected to receive additional educational materials or questionnaires on a variety of topics of interest to specific researchers.
OBJECTIVE: The shift in health care delivery from a subspecialty to primary care system has transferred the responsibility of preventing osteoporotic fractures from specialists in metabolic bone disease to the web of physicians--family practitioners, general internists, pediatricians, and gynecologists--who provide the bulk of primary care. The challenge for this group of physicians is to decrease the rising prevalence of osteoporotic hip and vertebral fractures while operating within the cost parameters. It is the goal of this brief summary to provide primary practitioners with focused guidelines for the management of postmenopausal osteoporosis based on new and exciting developments. Prevention and treatment will change rapidly over the next decade and these advances will require changes in these recommendations. DESIGN: We identified patients at risk for osteoporosis and provided indications for bone mass measurement, criteria for diagnosis of osteoporosis, therapeutic interventions, and biochemical markers of the disease. RESULTS: Prevention and treatment are discussed, including hormone replacement therapy and use of calcitonin, sodium fluoride, bisphosphonates, and serum estrogen receptor modulators. CONCLUSIONS: Postmenopausal osteoporosis should no longer be an accepted process of aging. It is both preventable and treatable. Primary care physicians must proactively prevent and treat osteoporosis in their daily practice, and combination therapies are suggested.
As databases in the human genome project proliferate, it is important for users of one genomic database to identify similar or inconsistent data in other autonomously developed genomic databases. To do so, the user needs to issue the same query across multiple databases. We describe an approach that allows a query issued against one database to be automatically mapped to an equivalent query against another structurally different database. Our approach features two components: 1) a database designed to capture knowledge (metadata) that describes the correspondences among individual database components and 2) a module that utilizes the metadata to perform query mappings. As a demonstration, we apply our query mapping approach to two chromosome map databases (DB/12 and GDB).
The epidermal growth factor receptor (EGFR) is overexpressed in a significant percentage of carcinomas and contributes to the malignant phenotype. CP-358,774 is a directly acting inhibitor of human EGFR tyrosine kinase with an IC50 of 2 nM and reduces EGFR autophosphorylation in intact tumor cells with an IC50 of 20 nM. This inhibition is selective for EGFR tyrosine kinase relative to other tyrosine kinases we have examined, both in assays of isolated kinases and whole cells. At doses of 100 mg/kg, CP-358,774 completely prevents EGF-induced autophosphorylation of EGFR in human HN5 tumors growing as xenografts in athymic mice and of the hepatic EGFR of the treated mice. CP-358,774 inhibits the proliferation of DiFi human colon tumor cells at submicromolar concentrations in cell culture and blocks cell cycle progression at the G1 phase. This inhibitor produces a marked accumulation of retinoblastoma protein in its underphosphorylated form and accumulation of p27KIP1 in DiFi cells, which may contribute to the cell cycle block. Inhibition of the EGFR also triggers apoptosis in these cells as determined by formation of DNA fragments and other criteria. These results indicate that CP-358,774 has potential for the treatment of tumors that are dependent on the EGFR pathway for proliferation or survival.
AIMS: (1) To evaluate the acceptability and validity of an intervention based on urine tests for diagnosis and treatment of gonorrhoea and chlamydia in men in remote Aboriginal communities. (2) To provide a prevalence estimate of these infections in the male population in the surveyed communities. METHODS: First-void urine samples from 460 men in remote communities and 33 men in the Alice Springs Gaol were tested for gonorrhoea and chlamydia with at least one of polymerase chain reaction (PCR), enzyme immunoassay (EIA) and culture (gonorrhoea only). RESULTS: One hundred and three men (20.9%) were infected with gonorrhoea or chlamydia. The prevalence of infection for gonorrhoea only was 11.7%, for chlamydia only 4.1% and for dual infection 5.1%. Eighty-eight infected men and 45 of their sexual partners were recorded as having been treated within two months of testing. PCR tests detected the largest number of infections and were the easiest to use. CONCLUSIONS: The prevalence of these infections was higher than anticipated. Urine PCR tests were acceptable to men and are well suited to the remote-community setting. As an effective alternative to urethral swabs, they permit a range of community-based strategies to address high rates of infection with gonorrhoea and chlamydia.
Data from a survey of 7722 15-16 year old school students in the United Kingdom were used to examine relationships between family structure and using alcohol, tobacco and illicit drugs. Respondents living with both parents were significantly less likely to participate in all of these, with girls more affected, particularly as regards cigarette smoking and illicit drugs. For other families, it made little further difference whether the mother, the father or both were absent. The effects were reduced on controlling four other variables. The latter were: psychological symptoms, social support, involvement in hobbies and reading, and engagement in behaviours such as riding mopeds, going out with friends, aggression and delinquency. It is suggested that these variables may mediate the effects of family structure.
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Programme Budgeting (PB) has been widely promoted as a model for the better conduct of the work of Health Authorities in the National Health Service in the United Kingdom. This paper reports on a project which looked at the development of PB in Newcastle and North Tyneside Health Authority (NNTHA), concentrating on the construction of a computerised tool for the compilation and analysis of programme budgets. The main activities carried out were a survey of user requirements for PB, a survey of data availability, the collection of data to construct programme budgets, and development of a relational database for storing and manipulating PB information. The main source of data was the Contract Minimum Data Set, which was supplemented by data from a number of other sources to give comprehensive information on spending in NNTHA. Costed activity data were produced, which could be aggregated in a large number of ways, such as by care setting (inpatient, outpatient, community, general practice, etc.), disease group (ICD9 chapter headings), case mix (Healthcare Resource Groups) and socio-demographic variables (age/sex, locality of GPs practice).
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Two groups of prelingually deaf children and a hearing control group participated in an experiment examining the effect of communication mode on the development of phonemic awareness. Sixteen of the deaf students (mean grade 6.9) were trained orally, using spoken language as their principal means for communication at home and at school. Another 16 deaf students (mean grade 6.9), all of them deaf children of deaf parents, acquired sign language as their primary language. The mean grade of the hearing control group was 6.5. The performance of the two deaf groups indicates that permanent auditory deprivation leads to substantially reduced phonemic awareness but does not entirely block its development. Contrary to expectation, the development of phonemic awareness in individuals with impaired hearing was not significantly affected by their preferred communication mode. Results further suggested that, for deaf individuals with excellent skills in sign language, the functional impairment caused by prelingual deafness may be restricted to the processing of phonological information.
Six cases of the Ganser syndrome have been previously described in the literature and are reviewed here. They are imperfect representations of the originally described syndrome. This article describes a case of the Ganser syndrome in a 12-year-old boy who, after a mild head injury, presented with three of four of the core symptoms. The nature of the Ganser syndrome remains unclear, but this case study highlights dissociation and abnormal illness behavior as being important in the production of the symptoms. Classically the course is short-lived, although this report raises the possibilities of a much more chronic course.
As part of an ongoing study developing and evaluating the use of programme budgeting (PB) and marginal analysis (MA) within purchasing organizations, conducts a survey of a health authorities' requirements of a decision-making tool based on PBMA. PB is a management decision-making system. It provides a summary of resource use categorized according to the programme or end product to which it applies. This explicit description of current activities focuses attention on competition for resources among programmes and on the effectiveness of resource use within programmes. MA is an economist's tool to evaluate options for changing the balance of resource use between or within programmes. Finds general support for PBMA techniques, although this waned with the higher functions of the tool. There was consensus that a health authority ought to know fundamentals like, for example, what proportion it spends on tackling coronary heart disease; and a majority view that PB will assist in revealing the key margins for service review.
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The regulatory process of motilin release was studied in segments of canine jejunum isolated and perfused ex vivo. The secretion of motilin in the effluent venous system of the isolated intestine was measured by radioimmunoassay in response to various pharmacological agents injected intra-arterially. Muscarinie agonist and antagonist, respectively, increased and decreased the release of motilin. The stimulatory effect of carbachol was still documented after tetrodotoxin (10(-5) M) was injected in the system to block neural influence on M cells. Bombesin and morphine also increased the release of motilin. The effect of bombesin was still documented in the presence of atropine or tetrodotoxin, but the stimulatory morphine effect was blocked by atropine. Both phenylephrine and octreotide decreased the release of motilin stimulated by carbachol in a jejunal segment pretreated and denervated with tetrodotoxin. Therefore, a revised model for the regulation of motilin release from M cells of intestinal mucosa can now be proposed. Cholinergic and bombesin receptors are present on M cells to encode a stimulatory signal, whereas adrenergic and somatostatin receptors are responsible for inhibitory transmission. The stimulatory effect of morphine is mediated via a muscarinic transmitter.
PURPOSE: A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens. Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study. PATIENTS AND METHODS: Thirty-five consecutive patients were accrued in two institutions (22 in one and 13 in the other). All had progressive disease after either cisplatin or carboplatin and paclitaxel, or at least one platinum-based and one paclitaxel-based regimen. Patients received intravenous (I.V.) liposomal doxorubicin 50 mg/m2 every 3 weeks with a dose reduction to 40 mg/m2 in the event of grade 3 or 4 toxicities, or a lengthening of the interval to 4 weeks (and occasionally to 5 weeks) with persistence of grade 1 or 2 toxicities beyond 3 weeks. RESULTS: Nine clinical responses (one complete response [CR], eight partial responses [PRs]) were observed in 35 patients (25.7%), with seven of these having been confirmed by two consecutive computed tomographic (CT) measurements. The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24+ months (median, 11 months). Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities (either hand-foot syndrome or stomatitis), with dose modifications, the treatment was very well tolerated. Nausea that was clearly attributable to the drug, hair loss, extravasation necrosis, or decreases in ejection fraction did not occur. CONCLUSION: Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel. The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity. This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients.
This paper presents results of the evaluation of an intervention designed for northeastern Thai villages and particularly for village women. The intervention was based on established principles of behavior change, social learning theory, and community health promotion, and it was grounded in elicitation research. A total of 600 women and 479 men and 12 villages participated in the evaluation which used data collected from face-to-face knowledge, attitude, practices (KAP) surveys, focus groups, and village meetings in a quasi-experimental pre- and post-control group design. Eight of the nine outcome goals set for the intervention were achieved with significant increases in married women taking the initiative in reducing the risk posed to them by the sexual activities of their husbands.