Obliquity-paced Pliocene West Antarctic ice sheet oscillations.

Thirty years after oxygen isotope records from microfossils deposited in ocean sediments confirmed the hypothesis that variations in the Earth's orbital geometry control the ice ages, fundamental questions remain over the response of the Antarctic ice sheets to orbital cycles. Furthermore, an understanding of the behaviour of the marine-based West Antarctic ice sheet (WAIS) during the 'warmer-than-present' early-Pliocene epoch ( approximately 5-3 Myr ago) is needed to better constrain the possible range of ice-sheet behaviour in the context of future global warming. Here we present a marine glacial record from the upper 600 m of the AND-1B sediment core recovered from beneath the northwest part of the Ross ice shelf by the ANDRILL programme and demonstrate well-dated, approximately 40-kyr cyclic variations in ice-sheet extent linked to cycles in insolation influenced by changes in the Earth's axial tilt (obliquity) during the Pliocene. Our data provide direct evidence for orbitally induced oscillations in the WAIS, which periodically collapsed, resulting in a switch from grounded ice, or ice shelves, to open waters in the Ross embayment when planetary temperatures were up to approximately 3 degrees C warmer than today and atmospheric CO(2) concentration was as high as approximately 400 p.p.m.v. (refs 5, 6). The evidence is consistent with a new ice-sheet/ice-shelf model that simulates fluctuations in Antarctic ice volume of up to +7 m in equivalent sea level associated with the loss of the WAIS and up to +3 m in equivalent sea level from the East Antarctic ice sheet, in response to ocean-induced melting paced by obliquity. During interglacial times, diatomaceous sediments indicate high surface-water productivity, minimal summer sea ice and air temperatures above freezing, suggesting an additional influence of surface melt under conditions of elevated CO(2).

How to develop and implement a program to continuously demonstrate the value of clinical pharmacy services.

This paper summarizes key elements that support the success of clinical pharmacy services to continuously improve the quality of drug therapy. Five drivers identify a successful model for continuously demonstrating the value of clinical pharmacy services: knowing the organizational culture; providing leadership; recruiting pharmacy sponsors; showing tenacity; and acting with management courage. Difficulties encountered when communicating the value of clinical pharmacy services within a health care organization usually arise because of failure to include one of these drivers.

Ambulatory care pharmacy services: has the agenda changed?

OBJECTIVE: To provide an extensive review of ambulatory care clinical pharmacy services and evaluate the services and research data in the field. DATA SOURCES: MEDLINE was searched from January 1992 through July 1999. Search terms included pharmacy, clinical pharmacy, and pharmaceutical care, cross-referenced with ambulatory care, primary care, family medicine, and managed care. STUDY SELECTION: Relevant peer-reviewed studies and reports since our previous article in 1992 were selected and described. Literature prior to 1992 was briefly reviewed. DATA SYNTHESIS: The relevant literature was reviewed and some examples from the authors' institutions are provided. Much research has continued to be published documenting the value of clinical pharmacy services in ambulatory care, including in community pharmacy, anticoagulation services, family medicine, primary care clinics, Veterans Affairs Medical Centers, and managed care. However, these innovative services are underrepresented in the community at large. The vast majority of the public does not have access to these types of services. CONCLUSIONS: There will be continued and dramatic expansion of ambulatory care pharmacy services in the new decade beginning in the year 2000. It will be critical that standards of practice be very high. We believe there is a critical need for visible demonstration projects and large multicenter research projects that demonstrate the value of these services.

Antiulcer prescribing program in a state correctional system.

OBJECTIVE: To describe a formulary antiulcer agent prescribing program developed as the result of a drug use evaluation (DUE). Program implementation, methods, cost impact, and results of a follow-up DUE are provided. BACKGROUND: The institution is a 51,000-bed correctional system consisting of 40 separate units each containing an ambulatory care clinic. Medication orders are transmitted via mainframe computer system to one of four pharmacies, which collectively dispense an average of 4000 medication orders (30 days' supply) per day. METHODS: Results from the antiulcer agent (cimetidine, ranitidine, sucralfate) DUE revealed that the agents studied were prescribed in dosages and durations exceeding criteria developed by the Pharmacy and Therapeutics Committee. A program designed to reduce dosages to maintenance therapy after eight weeks at treatment dosage was developed by the Pharmacy and Therapeutics Committee with staff physician input. Antiulcer agent use and expenditures were followed and a follow-up DUE was completed seven months after program implementation. Antacid use and frequency of upper gastrointestinal studies that were ordered were followed. RESULTS: The follow-up DUE showed the mean daily dosage for prescribed histamine2-receptor antagonists decreased (cimetidine from 694 to 454 mg, ranitidine from 280 to 183 mg) and the mean duration of therapy decreased from 14 to 10 months. The percentage of patients with potentially significant drug interactions decreased from 14.2 to 6.5 percent. The mean number of antiulcer agents dosage units dispensed per month decreased by 24,461 units, resulting in a projected annual savings of $327,273. There were no identifiable clinically important changes in the use of antacid products or prescribing of upper gastrointestinal studies. CONCLUSIONS: A cost-savings program sponsored by the pharmacy and therapeutics committee decreased costs, corrected prescribing to more closely meet preset criteria, and produced no discernable unfavorable effect on patient care.

Evaluation of glipizide and glyburide in a health maintenance organization.

OBJECTIVE: To determine if there was a difference in the long-term glycemic control, average daily dose, and cost of therapy in patients with noninsulin-dependent diabetes mellitus (NIDDM) treated with glyburide and glipizide in a health maintenance organization (HMO). DESIGN: Retrospective evaluation of medical and pharmacy records. SETTING: Multispecialty group practice HMO. PATIENTS: 140 NIDDM patients being treated with either glyburide (n = 70) or glipizide (n = 70) were randomly selected from the populations of patients receiving either drug using computerized pharmacy records. MAIN OUTCOME MEASURE: Mean daily doses and blood glucose measurements (fasting blood glucose, random blood glucose, hemoglobin A1C) were stratified in 3-month periods from the time the drug therapy was started or the patient first presented to the clinic for a total of 18 months. Long-term glycemic control was defined as fasting blood glucose less than 8.33 mmol/L (150 mg/dL). RESULTS: The groups were comparable with regard to age (53.4 y glyburide, 56.7 y glipizide), gender (43 M:27 F glyburide, 47 M:23 F glipizide), race (38 W/16 B/16 H glyburide, 45 W/16 B/9 H glipizide), concurrent medical conditions, adverse effects, and compliance. Long-term glycemic control was similar in both groups. Although the number of subjects who were controlled (by definition) tended to be greater in the glyburide group, no clinical or statistical difference was found. There was no statistical difference in mean daily dose between the ethnic groups, but the small numbers preclude further analysis. The glipizide group had a larger percentage increase in dose within the first year than did the glyburide group; however, the percentage increase from the 3-month dose was similar after 18 months (22.7 percent glyburide, 27.5 percent glipizide.) Average daily cost of therapy, based on mean daily dose, was slightly lower for glyburide-treated patients. CONCLUSIONS: If glycemic control is similar with glyburide and glipizide, as seen in this study, economic considerations regarding choice of therapy and formulary inclusion may be appropriate.

Ambulatory care pharmacy services: the incomplete agenda.

OBJECTIVE: To review studies that document the impact of clinical pharmacy services in ambulatory care settings and to propose standards of practice and resource allocation needs in ambulatory care. DATA SOURCES: English-language literature from 1970 through 1991 was reviewed and the representative literature is described. STUDY SELECTION: Studies were selected that examined the impact of clinical pharmacy services on patient outcomes and costs. Studies that evaluated pharmacist consultations by blind peer-review panels were also evaluated. DATA EXTRACTION: Trials were assessed based on their methodologies and ability to assess the value of clinical pharmacy services on patient outcomes. DATA SYNTHESIS: Numerous studies from the past 20 years are described illustrating the impact that ambulatory care pharmacy practitioners have made on patient care. These studies demonstrate that clinical pharmacists in ambulatory care not only serve as consultants on pharmacotherapy issues, but also can improve the quality of care for individual patients. CONCLUSIONS: Based on the studies cited and the needs of ambulatory patients, this article highlights the authors' views on what the standards of practice should be for ambulatory care practitioners and where resources should be allocated as ambulatory programs are expanded.

Perceived purpose of prescription drugs: the Iowa 65+ Rural Health Study.

In order to assess elderly patients' knowledge of their medications, the Iowa 65+ Rural Health Study asked a rural, elderly population the purpose of their prescription drugs. Ten percent of all drug purposes reported were considered inappropriate by our criteria. There was some variability between therapeutic categories and their frequency of purpose misperception. For 40 percent of drugs whose purpose was inappropriate, the respondent reported another drug for which that purpose would have been appropriate. Respondents were as likely to state a medication's appropriate purpose whether it had been dispensed by a pharmacy or a physician. The highest percentage of drugs whose purpose was appropriately perceived was dispensed by mail-order pharmacies.

Effect of clinical pharmacy services on the quality of family practice physician prescribing and medication costs.

This study assessed the impact of physician exposure to clinical pharmacy services on the appropriateness of physician prescribing and on medication costs. Two study sites were used: FPC (primary resident training office without clinical pharmacist) and PMC (satellite office with clinical pharmacist). The same physicians provided care at both study sites. Exposed patient encounters were selected from encounters during each resident's rotation at the PMC satellite. Unexposed patient encounters were selected from encounters at the FPC immediately prior to each resident's exposure to clinical pharmacy services. A blind review panel evaluated case abstracts of the patient encounters for appropriateness of drug choice, daily dosage, dosing interval, duration of treatment, clarity of instructions, and monitoring data; potential severity of the patient problem; and difficulty of the clinical decision. After adjusting for covariables (potential severity, difficulty, patient age, sex, Medicaid status, therapeutic category, and type of medical problem), physician-patient encounters in which family practice residents were exposed to clinical pharmacy services were rated significantly more appropriate for choice of drug prescribed, daily dosage chosen, dosing interval selected, clarity of prescription instructions, and monitoring data. Costs of acute medications, as measured by average wholesale price per day, per dose, and per treatment course, were also significantly lower for clinical pharmacy-exposed physician-patient encounters.

Documentation and appropriateness of prescribing for Veterans Administration ambulatory-care patients.

Information about active prescriptions in pharmacy medication profiles of outpatients at a Veterans Administration (VA) medical center was compared with corresponding information in the medical records to determine the completeness of prescription documentation. Appropriateness of prescribing was assessed by comparison with explicit criteria. Information about the active prescriptions included in 300 randomly selected patient medication profiles was collected from August to October 1984. The completeness of prescription information documentation was determined by comparing the data obtained from the patient's medication profile with the corresponding medical record entry. Medication profiles were screened for three types of potentially inappropriate prescribing: inappropriate daily dosage, inappropriate duplication of therapy, and interacting drug combinations. A total of 287 patient medication profiles and medical records were studied. Only 60 medical records (20.9%) had accurate documentation of all drug names, drug strengths, and directions for use when compared with the medication profiles. Evidence of potentially inappropriate prescribing was present in medication profiles of 43.4% of the patients. Medical record documentation was insufficient for a provider to detect 50.0% of the dosage deviations, 33.3% of the duplications of therapy, and 26.1% of the drug-drug interactions. The probability that evidence of potentially inappropriate prescribing would be present in a medication profile increased as the number of drugs per patient increased. However, there was no significant positive association between insufficient medical-record documentation and the presence of any of the three indicators of potentially inappropriate prescribing in the medication profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Medication use characteristics in the elderly: the Iowa 65+ Rural Health Study.

Medication use was studied in a rural, elderly population. Household interviews were conducted of 3,467 individuals aged 65 years or older. A total of 9,955 prescription or nonprescription drugs were reported by the respondents. The overall mean number of drugs per respondent was 2.87, while 12% of all respondents were not taking any drugs. Mean prescription and overall drug use increased significantly with increasing age (P less than .001), while mean nonprescription drug use was relatively constant across age groups. Significantly more women were prescription and nonprescription drug users. Directions for scheduled daily dosing accounted for 75% of all directions. The majority of prescription and nonprescription drugs had been taken on the previous day. General practitioners accounted for more prescription drugs (39.7%) than any other medical specialty. The most frequently stated purpose was cardiovascular for prescription drugs and musculoskeletal for nonprescription drugs. The three most frequent prescription drug therapeutic categories were cardiovascular (54.7%), central nervous system (CNS) agents (11.4%), and analgesics (9.4%). For nonprescription drugs, the three most frequent therapeutic categories were analgesics (39.6%), vitamins and minerals (32.9%), and laxatives (14.1%). Implications of these findings are discussed.

Dilemmas in primary care: antibiotic treatment of acute otitis media.

Antibiotic treatment of acute otitis media (AOM) accounts for a significant number of all antibiotic prescriptions each year. In the primary care setting, initial antibiotic selection is rarely based on direct evidence, such as cultures of middle ear fluid. Initial antibiotic therapy by the primary care practitioner involves the evaluation and application of information related to prevalence of infecting organisms; in vitro antibiotic spectrum and penetration into middle ear fluid; initial cure rate, relapse and recurrence rates; and antibiotic cost, safety, and convenience. The influence of these factors on the initial antibiotic choice for AOM is reviewed. Several therapeutic dilemmas confronting the prescriber are discussed and a rational approach to initial antibiotic therapy is presented.

The effect of clinical pharmacy services on family practice residents' attitudes: a nationwide study.

A nationwide study investigated the attitudes of family practice residents toward: interdisciplinary health care teams in family practice; the clinical pharmacist as a member of the health care team; and the utility of clinical pharmacist involvement in private family practice offices. A random sample of 174 family practice residency programs was selected for study. First-year residents comprised the sample population. Based on the response of the directors, programs were assigned to experimental (programs offering clinical pharmacy services) or control (no clinical pharmacy services) groups. Completed attitudinal instruments were received from 158 resident respondents in the experimental group and 153 resident respondents from the control group. The reliability coefficient of the returned questionnaires was 0.901 by the split-halves method. Residents in the experimental group had significantly more favorable attitudes than those residents in the control group on several scales. These scales included the clinical pharmacist's participation on the health care team, utility of a clinical pharmacist in a private practice setting, desirability of hiring a clinical pharmacist, and the desirability of practicing with a multidisciplinary health care team. These results support the hypothesis that exposure to clinical pharmacy services can significantly affect physician resident's attitudes toward clinical pharmacy.

The use of subtherapeutic antibiotics in animal feed and its implications on human health.

Antibiotics were approved for use as animal feed additives in 1950 after it was discovered that their use increased growth rate, improved feed utilization, and reduced mortality and morbidity from clinical and subclinical infections in animals. Subtherapeutic use of antibiotics in animal feed grew extensively and concern has arisen that this "indiscriminate" use of antibiotics could lead to increased numbers of antimicrobial-resistant bacteria and ultimately compromise treatment of human bacterial infections. Three recently published studies seem to indicate that animal-to-man transmission of antimicrobial-resistant bacteria is possible. Increased debate on the continuing allowance of antibiotic feed additives has ensued. The National Resources Defense Council has recently petitioned the FDA to disallow penicillin and tetracycline use in animal feed, and legislation has been introduced in the U.S. House of Representatives that would limit the subtherapeutic use of antibiotics in animal feed. Experts have predicted that meat prices would increase and meat quality would decrease if antibiotics are disallowed as a feed additive. It is the opinion of the authors that there is no conclusive evidence at this time to support the premise that subtherapeutic use of antibiotics in animal feed poses a greater threat to human health than if antibiotic feed additives were banned.

Transport of conjugates of toxicants by blood proteins.

Binding of naphthol and its glucoside and glucuronide conjugates by blood proteins was studied in vitro and in vivo. Binding was found to be primarily to the albumin fraction of human blood and the binding constants were moderate to low. Both in vivo (mice) and in vitro (human) experiments suggest that a substantial portion of naphthol and two conjugates are transported in bound form to the site of elimination.

Evaluation of family physician prescribing: influence of the clinical pharmacist.

This study was designed to determine whether prescribing patterns in family practice residency training offices were more favorable in offices with clinical pharmacists. Two family practice residency training offices with clinical pharmacists and two offices without clinical pharmacists served as study sites. At each office, 100 prescription copies were selected by stratified random sampling, and a case abstract was constructed from the medical record. An additional 38 prescriptions that resulted from clinical pharmacist consultation were studied. A blinded review panel evaluated the cases for appropriateness of drug choice and dose and anticipated benefit of the prescription. Prescriptions from offices with clinical pharmacists and consult prescriptions were rated significantly more favorably both for drug choice and drug dose (p less than 0.02). These data suggest that clinical pharmacists involved in family practice residency programs may refine and improve otherwise acceptable prescribing.