Assembling and manipulating two-dimensional colloidal crystals with movable nanomagnets.

We study crystallization of paramagnetic beads in a magnetic field gradient generated by one-dimensional nanomagnets. The pressure in such a system depends on both the magnetic forces and the hydrodynamic flow, and we estimate the flow threshold for disassembling the crystal near the magnetic potential barrier. A number of different defects have been observed which fluctuate in shape or propagate along the crystal, and it is found that the defect density increases away from the nanomagnet. We also study the melting of the crystal/fluid system after removal of the nanomagnet and demonstrate that the bond-oriental order parameter decreases with time. The nanomagnet can be moved in a controlled manner by a weak external magnetic field, and at sufficiently large driving velocities we observe self-healing crack formation characterized by a roughening of the lattice as well as gap formation. Finally, when confined between two oscillating nanomagnets, the colloidal crystal is shown to break up and form dipolar chains above a certain oscillation frequency.

Influence of a financial incentive on cognitive services: CARE project design/implementation.

OBJECTIVE: To describe the design and methods of the Washington State Cognitive Activities and Reimbursement Effectiveness (CARE) Project, a demonstration project in which community pharmacies were paid for cognitive services (CS) provided to Medicaid patients, its evaluation objectives, and the extent to which implementation objectives were achieved. DESIGN: Prospective randomized trial. Community pharmacies were allocated to a documentation-and-payment group, documentation-only group, and "silent" control group. CS were reported using a problem-intervention-result classification system embedded within a pseudo-National Drug Code format. Management strategies included use of area coordinators. SETTING: Pharmacies serving ambulatory Medicaid patients in the state of Washington, excluding staff-model health maintenance organization pharmacies and pharmacies predominantly serving long-term-care residents. PARTICIPANTS: 200 community pharmacies (110 treatment; 90 control), with another 100 randomly selected pharmacies as a silent control group. INTERVENTIONS: A modest monthly stipend. The treatment group billed Medicaid for each documented CS associated with a drug therapy-related problem. All participants received training in documentation methods. A unique coding scheme allowed documentation of CS within the constraints of the Medicaid program. Data edit checks and feedback were used to ensure data quality and completeness. Area coordinators were used to facilitate training, compliance with study procedures, and participation. MAIN OUTCOME MEASURES: Participation rates, documentation rates, coding scheme revision, data quality and completeness rates, and effectiveness of area coordinators. RESULTS: Pharmacists documented more than 20,240 CS records. Approximately 89% of records passed edit checks, and 94% did so after modification. Nearly 83% could be linked to a paid drug or CS claim. The coding system was sufficient, with minor modifications, to account for all interventions documented. Area coordinators did not function as expected. CONCLUSION: A system for documentation and payment of pharmacists' CS to Medicaid recipients was implemented successfully and relatively easily in community pharmacies.

Characteristics of pharmacies and pharmacists associated with the provision of cognitive services in the community setting.

OBJECTIVE: To determine the influence of payment, pharmacy setting characteristics, pharmacist demographics, practice setting, and attitudinal characteristics on whether cognitive services (CS) were performed by pharmacists, and the volume of CS performed. DESIGN: Prospective randomized trial. Community pharmacies were randomized to a documentation-and-payment group (study group) and a documentation-only group (control). Participating pharmacies and pharmacists were surveyed by mail, and responses were linked to a documented CS database. SETTING: Community pharmacies serving ambulatory Medicaid patients in the state of Washington, excluding health maintenance organization pharmacies and pharmacies predominantly serving long-term care residents. PARTICIPANTS: 200 community pharmacies and their pharmacists (110 study, 90 control) participating in the Washington State Cognitive Activities and Reimbursement Effectiveness (CARE) Project. INTERVENTION: Payment for CS. All participants documented CS. Study group pharmacies billed Medicaid for services performed in identifying and resolving drug therapy-related problems. MAIN OUTCOME MEASURE: Documentation of CS. RESULTS: Documentation of CS was more likely if the pharmacist was an owner or manager, if documentation was not perceived as burdensome, and if the pharmacy had a low ratio of prescription to total sales. Higher documentation rates were associated with study group status, lower pharmacy prescription volume as a percentage of total sales, and a higher percentage of prescriptions billed to Medicaid. Among pharmacists, two setting variables--medical center location and rural location--were associated with higher documentation rates. CONCLUSION: Performance of CS was strongly affected by payment and other situational factors, including practice setting and volume of prescriptions dispensed. Pharmacies and pharmacists were also more likely to perform CS if the target patient population represented a relatively large percentage of that pharmacy's patient clientele.

Research and development costs for new drugs by therapeutic category. A study of the US pharmaceutical industry.

The clinical period (i.e. clinical trial and long term animal testing) development costs of a random sample of new chemical entities (NCEs) were examined for differences in average cost. All of the NCEs studied were first tested in humans between 1970 and 1982, and were classified for the purposes of the study by therapeutic class. The costs of unsuccessful projects were included with those of projects that resulted in US marketing approval. Including income forgone from expending funds before returns are earned ('time costs'), the capitalised (i.e. out-of-pocket plus time) clinical period costs per approved NCE were $US70, $US98, $US103 and $US163 million (1993 dollars) for anti-infective, cardiovascular, neuropharmacological and nonsteroidal anti-inflammatory drugs, respectively. Combining the data for all therapeutic categories, the mean clinical period cost per approved NCE was $US93 million. Omitting costs associated with unsuccessful projects, the mean capitalised clinical period costs for approved NCEs ranged from $US7.1 million (for topical steroids) to $US66.7 million (for cardiovascular agents) [1993 dollars]. The estimates of total clinical period costs per approved NCE depend on average out-of-pocket clinical phase costs, attrition rates across phases (i.e. the rates at which compounds drop out of active testing), the probability of marketing approval, and development and regulatory review times. Phase attrition and approval rates are the most important sources of variability in total clinical period costs between therapeutic categories. Development cost estimates by therapeutic category did not correlate strongly with US sales in the fifth year of marketing. Cardiovascular NCEs had much higher than average sales revenues, but clinical development costs for these drugs were only slightly above average. Conversely, nonsteroidal anti-inflammatory drugs attained average sales revenues, but had much higher than average development costs.

Omnibus Budget Reconciliation Act of 1990 and voluntarism: logistic regression analysis of pharmacist responsibility.

OBJECTIVE: To examine the relationship between pharmacists' willingness to assume further professional responsibilities, as measured by attitudes to the Omnibus Budget Reconciliation Act of 1990 (OBRA '90) requirements, and their attitudes toward voluntarism as their responsibility to society and their level of interest in their jobs. DESIGN: A survey was distributed to a convenience sample of 443 pharmacists who were asked to indicate their responses on a number of items. SETTING: Surveys were distributed to participants in an annual pharmacy continuing education program. PARTICIPANTS: The response rate was 65 percent with completed surveys from 290 Florida pharmacists who were typically male (73 percent) and practicing in the community setting (39 percent) for over 25 years (33 percent). MAIN OUTCOMES: Questions were aimed at gathering the following information: (1) demographics; (2) attitudes concerning the benefits of the three OBRA '90 requirements: patient counseling, prospective drug-use review (DUR), and information recording; (3) attitudes toward voluntarism; and (4) job interest. RESULTS: Pharmacists tended to agree that all three of the OBRA '90 mandates will be beneficial. Fifty-six percent favored the prospective DUR requirements, while 68 percent favored the patient counseling requirements and 66 percent favored the information-recording requirements. Logistic regression analysis showed that unit increases in scaled responses, indicating more favorable attitudes toward believing that voluntarism was one's responsibility, increased the odds of favoring counseling by 38.7 percent and information recording by 32.4 percent. A similar directional relationship was found for the DUR requirement. Job interest did not add to the predictive ability of the variables already in the models. CONCLUSIONS: This study suggests a possible association between pharmacists' attitudes toward social responsibility and their acceptance of expanded professional responsibility.

Psychomimetic reactions after neurolept and propofol anaesthesia.

The purpose of this study was to compare the frequency of psychomimetic reactions after 24 h and 3 months following total intravenous anaesthesia with propofol and neurolept anaesthesia. Forty otherwise healthy female patients were randomly divided into two groups. All were undergoing elective gynaecological laparotomy for non-malignant disease. Nineteen patients were anaesthetized with droperidol, fentanyl, pancuronium, N2O/O2. Twenty patients received total intravenous anaesthesia with propofol, fentanyl and pancuronium. Twenty-four hours after the anaesthesia the patients were interviewed about their subjective experiences of anaesthesia and recovery. Three months after the operation the patients were sent a questionnaire concerning ability to work, sleep and memory disorders. After 24 h the anaesthesia was judged as good by 18 patients receiving propofol and 13 patients receiving NLA (n.s.). The recovery was judged as good by 16 patients in the propofol group and six patients in the NLA group (P < 0.05). Locked-in feelings were reported by one patient in the propofol group and ten patients in the NLA group (P < 0.01). Impairment of memory was reported by one patient in the propofol group and seven patients in the NLA group (P < 0.01). A questionnaire used after 3 months was answered by 18 patients in the propofol group and 17 patients in the NLA group. There were few complaints, and no differences were found between the two groups. In conclusion, total intravenous anaesthesia with propofol seems more acceptable than anaesthesia with neurolept as judged by the patients 24 h after anaesthesia. There were no differences between the two groups concerning psychomimetic reactions 3 months after anaesthesia.

Ultraviolet/ozone cleaning of carbon-contaminated optics.

It is shown that ozone generated by UV light can be used to clean carbon-contaminated synchrotronradiation optics.

Intraoral micro-identification discs.

Intraoral micro-identification discs have recently been utilized to provide a more permanent method of personal identification. A wafer of plastic or metal with a surface area of 2.5 to 5 mm2 and carrying identifying numbers and/or letters (indicia) is bonded to the buccal enamel surface of the posterior teeth. Personal identification can occur after the I.D. disc is identified and the indicia is read. Reading of photoreduced indicia requires the aid of a microscope subsequent to the removal of the microdisc. In situ reading of disc indicia is possible using low power handheld magnifiers if the size of the indicia approximates 0.3 mm. Computerization is an integral part of non-custom alpha/numeric type designs, but a custom disc carries a name, address, and other specific information unique to the manufacturer. The use of a computer improves access to the database and it decreases the amount of data placed on the disc. Microdisc bases may be fabricated using a mylar type plastic or they may be manufactured from a stainless steel blank. Plastic discs are constructed with an internal sandwich containing the photo-reduced indicia. Metal discs are marked with a photochemical etch or engraved with a computer driven YAG laser. Attachment of the disc to the enamel surface is accomplished by conventional etching and bonding techniques and are typically bonded to the buccal surface of the maxillary first permanent molar or the second primary molar. Clear composite bonding material covers the disc so that salivary contamination does not result in degradation of the indicia. Orthodontic style discs with a mesh back carry laser written information that may be cemented with conventional orthodontic bonding cement. Standardization of the indicia and overall design is considered to be an important aspect of patient and professional acceptance.

Cost of innovation in the pharmaceutical industry.

The research and development costs of 93 randomly selected new chemical entities (NCEs) were obtained from a survey of 12 U.S.-owned pharmaceutical firms. These data were used to estimate the pre-tax average cost of new drug development. The costs of abandoned NCEs were linked to the costs of NCEs that obtained marketing approval. For base case parameter values, the estimated out-of-pocket cost per approved NCE is $114 million (1987 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a 9% discount rate yielded an average cost estimate of $231 million (1987 dollars).

New pharmaceuticals reduce cost of illness.

The cost of illness includes not only the funds required to treat illness, but also the effect on the patient's quality of life. Recent concern about rising health costs have focused on the direct expenditures without noting that the cost of illness in terms of mortality and morbidity has declined significantly. Pharmaceuticals have played a major role in reducing the total cost of illness. Several studies of the cost-effectiveness of past introductions of vaccines and pharmaceuticals reveal large cost savings. Although the focus of most studies has been on major advances, the continuing process of less dramatic therapeutic improvements has significantly trimmed the cost of illness. Cost-benefit studies of new drugs or changes in drug use, while more difficult to perform, make it possible to influence the selection of therapy. Since pharmaceuticals represent less than 10% of total treatment costs, reduction in the cost of pharmaceutical products can only have a minor impact on the total cost of illness. Pharmaceuticals can reduce the cost of illness by providing alternative therapies that reduce direct treatment cost or improve the public health.