Safety and efficacy of retreatment with a bioengineered hyaluronate for painful osteoarthritis of the knee: results of the open-label Extension Study of the FLEXX Trial.

OBJECTIVE: To evaluate the safety of repeated intra-articular (IA) injections of Euflexxa® (1% sodium hyaluronate; IA--BioHA) for painful knee osteoarthritis (OA). DESIGN: Participants who completed the randomized, double-blind, 26-week FLEXX Trial comparing IA-BioHA to IA saline (IA-SA) for knee OA(1) received three weekly IA-BioHA injections in a 26-week Extension Study. Adverse events (AEs) were recorded and the effect of treatment on knee pain was measured immediately following a 50-foot walk test using a 100 mm visual analog scale (VAS). Responder rate, Medical Outcomes Study Short Form 36 scores, Patient's Global Assessment, and intake of rescue medication were also evaluated. RESULTS: The Extension Study included 433 subjects, 219 who received IA-BioHA and 214 who received IA-SA during the FLEXX Trial. Safety results from the Extension Study indicated that 43.4% (188/433) of subjects had AEs, of which 4.8% (21/433) were deemed treatment-related AEs. Two AEs in the Extension Study led to discontinuation, and no joint effusion was reported. Patients who continued with IA-BioHA in the Extension Study maintained their improvement from baseline, with an average reduction in pain in the VAS score of -3.5 mm. Patients initially treated with IA-SA in the FLEXX Trial also had a reduction in VAS score of -9.0 mm. Secondary efficacy variables also improved during the Extension Study. CONCLUSIONS: Repeat injections of IA-BioHA were effective, safe, well tolerated, and not associated with an increase in AEs, such as synovial effusions. Additional symptom improvements were noted for subjects who received either IA-BioHA or IA-SA in the FLEXX Trial. CLINICAL TRIAL REGISTRATION NUMBER: NCT00379236.

The SF-36 Health Survey as a generic outcome measure in clinical trials of patients with osteoarthritis and rheumatoid arthritis: tests of data quality, scaling assumptions and score reliability.

OBJECTIVE: To evaluate the psychometric assumptions underlying the construction and scoring of SF-36 scales and summary measures among clinical trial participants with arthritis. METHODS: Cross-sectional SF-36 data from the baseline assessment of adult patients (n = 1,016) participating in four placebo-controlled clinical trials of treatment for arthritis were analyzed with blinding as to treatment. Tests of the completeness of data, scaling assumptions, internal-consistency reliability, and factor structure of SF-36 scales were performed for the combined sample. Eligible participants had at least a 6-month history of moderate to severe osteoarthritis or rheumatoid arthritis of the knee or hip. Participants meeting inclusion criteria had undergone a washout period of 3-14 days before baseline assessment to bring about a flare state in osteoarthritis or rheumatoid arthritis symptoms. Baseline sample sizes for the three osteoarthritis trials were n = 121, n = 341, and n = 187. The baseline sample size for the rheumatoid arthritis trial was n = 367. The average age of participants was 60 years, and the majority were females (72%). Measured were functional health and well-being scales and physical and mental health summary measures from the SF-36 Health Survey acute form. RESULTS: Missing responses ranged from 0.0% to 1.5% across SF-36 items, and scale scores could be computed for 96.8% to 100% of participants across trials. In all four trials, item internal consistency tests were passed (91.4%-97.1%) and item discriminant validity tests were passed (96.9%-100.0%). Across the four trials, internal-consistency reliability coefficients ranged from a low of 0.75 to a high of 0.91 for the eight scales (median = 0.84), exceeding the minimum standards for group comparisons. Ceiling effects were minimal for most scales, and floor effects were noteworthy for the role physical and role emotional scales. Physical and mental health factors identified in previous studies were replicated. CONCLUSION: The SF-36 Health Survey proved to be a psychometrically sound tool for the assessment of the health status of adult participants in clinical trials of arthritis.

The SF-36 Health Survey as a generic outcome measure in clinical trials of patients with osteoarthritis and rheumatoid arthritis: relative validity of scales in relation to clinical measures of arthritis severity.

OBJECTIVE: To evaluate the validity of SF-36 Health Survey (SF-36) scale scores and summary measure scores to describe the health burden of arthritis and to be responsive to clinical indicators of arthritis severity used in four clinical trials. METHODS: Adults participating in four double-blinded, placebo-controlled clinical trials of therapy for osteoarthritis or rheumatoid arthritis were administered the SF-36 concurrent with clinical measures of disease severity (n = 1,016). Data were collected before treatment and 2 weeks after treatment. Mean SF-36 scores for all patients with arthritis at baseline were compared to a sociodemographically equivalent national norm to test the ability of the SF-36 to describe the burden of arthritis. To test the responsiveness of SF-36 scores to clinical measures of arthritis severity, mean SF-36 scale scores were compared across patients differing in arthritis severity before treatment. Two-week mean SF-36 change scores were compared across patients who improved in arthritis severity (responders) versus patients who did not improve (nonresponders). F-statistics and relative validity coefficients were computed to determine how well each SF-36 scale and summary measure discriminated among arthritis severity levels and distinguished treatment responders from nonresponders, relative to the best scale. RESULTS: Large and statistically significant differences in mean SF-36 scale scores and summary measures were found such that trial participants scored in worse health than a sociodemographically equivalent US general population norm. In addition, the largest SF-36 scale scores were found to significantly differ across clinically defined levels of arthritis severity. Finally, it was found that the SF-36 scales that best discriminate among arthritis severity groups cross-sectionally were also best at discriminating treatment responders from nonresponders. CONCLUSION: Results of this study support the validity of the SF-36 to document the health burden of arthritis and as a measure of generic health outcome for clinical trials of alternative treatments for osteoarthritis and rheumatoid arthritis patients.

The SF-36 Arthritis-Specific Health Index (ASHI): I. Development and cross-validation of scoring algorithms.

An arthritis-specific health index (ASHI) for the SF-36 Health Survey was developed by studying its responsiveness to changes in clinical indicators of arthritis severity. Longitudinal data from 1,076 patients participating in four placebo-controlled trials were analyzed. All had at least a 6-month history of moderate to severe osteoarthritis or rheumatoid arthritis of the knee or hip. All had undergone a washout period of 3 to 14 days before baseline assessment to bring about a flare state in osteoarthritis or rheumatoid arthritis symptoms. Their average age was 60 years and 72% were female. Change scores for the eight-scale SF-36 health profile (acute version) and five arthritis-specific measures of disease severity (knee pain on weight bearing, time to walk 50 feet, physician global evaluation of symptom severity and impact, patient global evaluation of symptom severity and impact, and pain intensity visual analogue scale) were computed by subtracting scores before treatment from scores at two-week follow-up. Canonical correlation methods were used to derive weights for changes in SF-36 scales to score a single index (ASHI) that maximized its correlation with changes in the set of five clinical measures of arthritis severity. The weights used to score the ASHI were cross-validated in a 25% holdout group (N = 144) from the first two osteoarthritis trials and in two additional osteoarthritis and rheumatoid arthritis trials (N = 530). Only one SF-36 canonical variate (ASHI) correlated significantly (F = 4.69, P < 0.0001) with the clinical canonical variate that served as the "criterion" measure of change in the severity of arthritis. Changes in the ASHI and clinical canonical variate were substantially correlated in the developmental sample (r = 0.628, P < 0.0001) and on cross-validation (r = 0.629, P < 0.0001). The clinical canonical variate correlated highly (r = 0.75-0.88) with changes in all but one of the five clinical measures (50-foot walk; r = 0.41). The pattern of correlations between changes in SF-36 scales and the ASHI indicated that ASHI is primarily a measure of bodily pain (r = 0.92) and other aspects of physical and role functioning and well-being (r = 0.69 for Role-Physical, r = 0.68 for Physical Functioning, r = 0.52 for Social Functioning, and r = 0.51 Vitality). The patterns of correlations between SF-36 scales and the ASHI were very similar across developmental and cross-validation samples. This research demonstrates the feasibility and generalizability of a single ASHI scored from changes in responses to the SF-36 Health Survey. The generic SF-36 health profile, which has already been shown to be useful in comparing arthritis with other diseases and treatments, can also be scored specifically to make it more useful in studies of osteoarthritis and rheumatoid arthritis.

The SF-36 Arthritis-Specific Health Index (ASHI): II. Tests of validity in four clinical trials.

OBJECTIVE: The SF-36 Arthritis-Specific Health Index (ASHI) was constructed to improve the responsiveness of the SF-36 Health Survey to changes in the severity of arthritis through the use of arthritis-specific scoring algorithms. This study compared the responsiveness of the ASHI and other generic scales and summary measures scored from the SF-36 in clinical trials of health outcomes for patients with arthritis. METHODS: Longitudinal data for patients (n = 835) participating in four placebo-controlled trials were analyzed. Study participants had at least a 6-month history of moderate to severe osteoarthritis or rheumatoid arthritis of the knee or hip. All had undergone a washout period of 3 to 14 days before baseline assessment to bring about a flare state in osteoarthritis or rheumatoid arthritis symptoms. Their average age was 60 years, and 72% were female. Responders and nonresponders were classified on the basis of physician assessments of changes in arthritis severity, with blinding as to treatment group; treated and untreated (placebo) groups were also compared. For the SF-36 ASHI, generic physical (PCS) and mental (MCS) component summary measures and each of eight subscales scored from the SF-36 (acute version) change scores were computed by subtracting scores before treatment from scores at 2-week follow-up. To evaluate empirical validity, analyses of variance were performed. For each measure, an F-ratio was computed for the comparison between clinically defined groups of responders and nonresponders and between groups of patients assigned to placebo versus drug therapy. Relative validity (RV) coefficients were computed for the ASHI in comparison with PCS, MCS, and the best SF-36 scale to determine which was more responsive. RESULTS: In analyses of each of the four trials and all trials combined, RV coefficients for the ASHI were higher than those for both of the generic SF-36 summary measures and for the most valid SF-36 scale (Bodily Pain), with only one exception. Across 40 tests of validity in distinguishing treated from untreated patients, the ASHI was 5% to 19% more valid than the best SF-36 scale (RV = 1.05-1.19; RV = 1.10 in all trials combined). The generic summary measures (PCS and MCS) were much less valid in these tests (RV = 0.67 and 0.27, respectively). In analyses of responders and nonresponders, RV coefficients for the ASHI ranged from 0.70 to 1.22 (RV = 1.04 in all trials combined), in comparison with the best SF-36 subscale, which was always Bodily Pain. RV coefficients were lower for PCS (RV = 0.75) and much lower than the MCS (RV = 0.18) in comparisons of treatment outcomes based on all trials combined. CONCLUSION: The ASHI appears to be more valid than the eight SF-36 scales and PCS and MCS summary measures for purposes of distinguishing between treated and untreated patients and between clinical responders and nonresponders. This study demonstrates the feasibility of improving the validity of the SF-36 through the use of arthritis-specific scoring while retaining the option of generic scoring, which makes it possible to also compare results across diseases and treatments.

Prevalence and cost of hospitalization for gastrointestinal complications related to peptic ulcers with bleeding or perforation: comparison of two national databases.

The purpose of this study was to determine the prevalence and cost of hospitalization for upper gastrointestinal complications, including peptic ulcers with hemorrhage or perforation. Upper gastrointestinal complications and corresponding economic data were obtained from two sources. The first was a 20% sample of all community hospital discharges (about 6 million per year) from 11 states for 1991 and 1992 Hospital Cost Utilization Project; HCUP-3). The second source of data was a claims database for employees of large US corporations and their dependents for 1992, 1993, and 1994 (about 3.5 million covered lives per year; MarketScan). A group of ICD-9 codes for the diagnosis of peptic and gastroduodenal ulcers with bleeding or perforation were used to identify hospital admissions because of upper gastrointestinal complications. Similar patterns were observed across the MarketScan and HCUP-3 databases regarding hospitalization with diagnoses related to gastrointestinal complications identified according to the ICD-9 codes. The average age of patients with upper gastrointestinal complications was 66 years in the HCUP-3 database and 52 years in the MarketScan database. The average annual rates of upper gastrointestinal complications as a primary or secondary diagnosis were 6.4 and 6.7 per 1000 discharges for 1991 and 1992, respectively (HCUP-3), and 4.3, 4.2, and 4.9 per 1000 admissions for 1992, 1993, and 1994, respectively (MarketScan). The average length of stay for upper gastrointestinal complications as a primary diagnosis was 7.8 days in 1991 and 7.5 days in 1992 (HCUP-3) and 6.1, 5.1, and 5.1 days in 1992, 1993, and 1994, respectively (MarketScan). The national average total charge for hospitalization for gastrointestinal problems as a primary diagnosis was $12,970 in 1991 and $14,294 in 1992 (HCUP-3). The average total reimbursement for hospitalizations related to upper gastrointestinal problems was $15,309 in 1992, $12,987 in 1993, and $13,150 in 1994 (MarketScan). Hospital admissions for upper gastrointestinal complications are expensive. The rate and cost per admission are higher for the older population. The results on the elements covered by both databases are consistent. Therefore the databases complement each other on the type of information abstracted.

Insomnia, health-related quality of life and healthcare resource consumption. A study of managed-care organisation enrollees.

OBJECTIVE: Insomnia is a prevalent sleep complaint which has been reported to be greatly associated with reduced health-related quality of life (HR-QOL) and increased healthcare resource use. This study documents the prevalence of insomnia, and its impact on patients' HR-QOL and healthcare resource use in managed-care settings in the US. DESIGN AND SETTING: A multi-site survey of 5 American Medical Group Association (AMGA) clinics was conducted. Each clinic mailed questionnaires to 1100 randomly selected individuals enrolled in its healthcare system and distributed questionnaires to 400 individuals during a clinic visit and prior to seeing a physician. The questionnaire was a form of the Health Status Questionnaire with the well-validated Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, a 3-question depression screen, a sleep questionnaire, demographic variables, and questions about medical encounters and prescription and over-the-counter (OTC) drug use. MAIN OUTCOME MEASURES AND RESULTS: Approximately one-third of managed-care enrollees in this study reported insomnia with daytime dysfunction. Individuals with insomnia reported lower HR-QOL scores and increased healthcare resource use compared with individuals with no insomnia. After controlling for demographic variable and comorbid conditions, the negative association of insomnia remained significant on all HR-QOL scores, emergency room visits, calls to the physician and OTC drug use. CONCLUSIONS: Insomnia is significantly associated with reduced HR-QOL and increased healthcare resource use in enrollees of managed-care organisations.

Prevalence of insomnia: a survey of the enrollees at five managed care organizations.

The purpose of the study was to assess the prevalence of and factors associated with insomnia among enrollees of managed care organizations (MCOs). A survey was distributed either by mail or during a clinic visit to 7,500 enrollees of five MCOs in the United States. The survey included a sleep questionnaire, demographic questions, and questions about medical encounters and prescription drug use. Three levels of insomnia (none; level I--difficulty initiating or maintaining sleep; level II--insomnia with daytime dysfunction) were defined from the responses. Comorbidities were determined by proxy from prescription drug use reported by respondents. A total of 3,447 survey responses were received, yielding a response rate of 46%. Level I and level II insomnia was reported by 13.5% and 32.5% of the respondents, respectively. Level II insomnia increased with decreasing education, income, and age and was more prevalent in women and non-Caucasians. Insomnia was significantly correlated with all daytime sleepiness and most nighttime disturbances factors. Fifty-two percent of all respondents reported at least one comorbid condition. Respondents with multiple comorbidities reported level II insomnia more frequently than those with no comorbidities. Only 0.9% of clinic visitors were seeing a physician specifically for sleep problems. Of those with level I and level II insomnia, only 5.5% and 11.6%, respectively, were taking prescription medications specifically for sleep problems; 11.2% and 21.4%, respectively, were taking over-the-counter medications for sleep. Insomnia occurs in MCO enrollees at rates comparable to those found in the general population. However, few patients with insomnia are actually being treated for their condition. Proper evaluation, diagnosis, and treatment of insomnia are warranted.

A comparative profile of clinical pharmacy activities for pharmacotherapists and residents in a university hospital.

Due to increasing financial pressure on maintaining and improving pharmacy services, there is a need for productivity data and time distribution among different activities for pharmacy practice residents and their faculty preceptors (pharmacotherapists). This study measured the clinical productivity of 13 residents and 25 pharmacotherapists for a 14-day period. The study identified the average time (minutes) and frequency spent each day on categories of activities, which included direct patient care, chart use, rounds, professional encounter, teaching, research, and administration. Results showed that the productivity profiles for residents and pharmacotherapists were comparable. Findings were utilized to defend the educational programs for the department and as a baseline for periodic monitoring of the productivity of these programs.

Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. A prospective observational cohort study.

BACKGROUND: Gastrointestinal tract (GI) complications associated with nonsteroidal anti-inflammatory drug (NSAID) use are the most common serious adverse drug reactions in the United States. Nonsteroidal anti-inflammatory drugs cause both minor GI side effects such as abdominal pain and vomiting and serious GI events such as ulcers and bleeding. This study evaluates the event rates for all NSAID-induced GI complications in patients with rheumatoid arthritis, describes the time course of these events, and evaluates the role of prophylactic therapy with antacids and H2 receptor antagonists. METHODS: We studied 1921 patients with rheumatoid arthritis from 8 ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers. Patients were selected for the study if they were treated with NSAIDs and had at least 2.5 years of observation available. Information on GI complications attributed to NSAIDs was obtained from validated patient self-reports collected every 6 months and supplemented by review of hospital records for all hospitalizations. RESULTS: Approximately 15% of the 1921 patients reported an NSAID-induced GI side effect during the 2.5 year observation period. Forty-two patients had a serious GI complication requiring hospitalization; 34 of these 42 patients did not have a preceding GI side effect. Patients who were taking antacids and H2 receptor antagonists did not have a significantly lower risk for serious GI complications than did those not taking such medications. Asymptomatic patients taking these medications had a significantly higher risk for GI complications compared with those who did not take these medications (standardized odds ratio, 2.14;95% confidence interval, 1.06-4.32). CONCLUSIONS: A large majority of patients with serious GI complications do not have preceding mild side effects. Prophylactic treatment with antacids and H2 receptor antagonists is of questionable value and may increase the risk for subsequent serious GI complications.

Risk factors for serious nonsteroidal-induced gastrointestinal complications: regression analysis of the MUCOSA trial.

OBJECTIVES: This analysis evaluated the clinical and demographic risk factors for a suspected, serious nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) complication in everyday clinical practice and calculated the risk reduction associated with misoprostol therapy in these "at-risk" patients. METHODS: Using logistic regression analysis, the data set from a randomized, parallel, placebo-controlled trial of misoprostol in 8,843 rheumatoid arthritis patients taking NSAIDs (the Misoprostol Ulcer Complications Outcomes Safety Assessment trial) was modeled to identify risk factors for GI adverse events. The dependent variable was defined as a "suspected serious GI complication," and the independent variables included demographic features, level of functional disability, presence of co-morbid diseases, use of certain drugs, and treatment arm. RESULTS: Two hundred forty-two suspected serious GI complications were observed; 102 occurred in the misoprostol treatment group (risk: 2.32%) and 140 in the placebo group (risk: 3.15%). Overall risk reduction due to misoprostol therapy was 26.6% (confidence interval 5.5%-42.9%, P < .05). However, in patient groups with identified risk factors, misoprostol use decreased the risk for an adverse GI event by 38.3%-87.3%. Specifically, those who benefitted significantly from therapy with misoprostol were patients with a history of peptic ulcer disease (risk reduction 52.4%), history of previous GI bleeding (risk reduction 50%), history of significant cardiovascular disease (risk reduction 38.3%), significant functional disability (risk reduction 87.2%), and patients whose symptoms required concomitant antacid use (risk reduction 48.3%). CONCLUSION: We conclude that in everyday practice, patients who require chronic NSAID therapy and who have specific clinical risk factors may benefit from misoprostol co-therapy.

Meta-analysis of controlled trials of drug therapy in mild chronic asthma: the role of inhaled corticosteroids.

OBJECTIVE: To determine the role of inhaled corticosteroids in the treatment of mild chronic asthma. SOURCE OF STUDIES: Searches of MEDLINE and Index Medicus for English language literature dealing with asthma and inhaled corticosteroids. DESIGN: All retrieved articles were subjected to predetermined criteria for inclusion in the meta-analysis. Inclusion criteria centered around randomized, double-blind studies reporting objective clinical endpoint(s) for subjects with mild chronic asthma who were treated for more than seven days. Studies that were included were not allowed to have any predetermined exclusion criteria. RESULTS: The literature search identified 129 articles, of which 41 satisfied some but not all of the criteria for inclusion. Five articles met all the criteria and were subjected to meta-analysis. The total number of subjects was 141. Peak expiratory flow rate (PEFR) was used as the objective endpoint for effect size calculation. Subjecting these five studies to quality review revealed a range of 0.607-0.741, with 1 as the highest attainable quality and 0 the lowest. Reported results for the different studies were found to be homogenous, thus allowing for the calculation of overall effect size. Inclusion of children in some of the studies added variance to the reported studies, but not to the point at which studies would be considered heterogenous. Effect sizes ranged between 0.41 and 0.89, and the overall weighted average effect size for PEFR was 0.59, with the calculated 95 percent confidence interval at 0.32 to 0.84. A tabulated display of binomial effect size for included trials provided ranges of success rates for treatment versus control values. Results of the studies were judged robust, as 92 studies reporting no significant effects are needed to turn the finding of the meta-analysis insignificant. CONCLUSIONS: Based on the results of the meta-analysis, the existing literature suggests a role for inhaled corticosteroids in the treatment of mild chronic asthma.

The use of pharmacoeconomic data in formulary selection.

Pharmacists are encouraged to improve their knowledge and use of pharmacoeconomic data in formulary selection. The formulary selection process has changed significantly in recent years. Among its most significant uses is its potential for cost containment strategies. An overview is presented of the origin as well as the potential impact of pharmacoeconomic data. The need to balance the economic benefit with the clinical advantages for any proposed new drug for formulary inclusion remains the most critical decision to be made by pharmacists.

1993 Bibliography: a 32-year literature review on the value and acceptance of ambulatory care provided by pharmacists.

OBJECTIVE: To review the published literature on the value and acceptance of pharmaceutical services provided by pharmacists in ambulatory care settings. DATA SOURCES AND METHODS: Articles published between 1960 and 1992. A MEDLINE search of the English-language literature was conducted using the terms pharmacists, services, and ambulatory settings. Studies were selected for inclusion if they addressed services provided by pharmacists in ambulatory settings and dealt with the cost of patient care, quality of care, or attitudinal surveys. Original research reports were summarized according to objectives, sample size, duration of study, methods, and findings. Summaries were categorized according to reported positive impact, negative impact, or investigational reports with no outcome. RESULTS: One hundred seventy articles were identified; 104 of them reported research data and were summarized. The 1970s was the most prolific decade for publication of articles reporting positive, negative, or no impact, which numbered 47, 20, and 37, respectively. Positive correlation was found among studies conducted according to predetermined protocol and reporting positive impact. Moreover, academic interest in pharmacy varied for the different decades. CONCLUSIONS: Collectively, this article provides references of the published reports on pharmacy professional services in ambulatory care settings, and a summary of the articles reporting research data. Additional and more focused research on pharmaceutical services in the community is needed. Emphasis is required on practicing pharmacists' attitudes toward nondispensing, patient-oriented pharmaceutical services; the impact of educational changes on the practice of pharmacy and consumers' attitudes and willingness to pay for services; and the link between patient outcome and pharmaceutical services.

Pharmacy agenda for change: the time is now.

In the midst of society's debate and focus on patient care and outcome, healthcare providers must articulate their strategic positioning to be part of the collective societal drive. Pharmacy as an integral component of healthcare provided, must also take the opportunity to create its own agenda for change. This agenda revolves around pharmacists agreeing on aspects of pharmaceutical care for which they are legally and ethically responsible. Pharmacists must also strive to gain social and cultural authority for those aspects for which the profession has accepted responsibility. Pharmacist action is needed to ensure appropriate drug therapy to the public.

Patient care contributions of clinical pharmacists in four ambulatory care clinics.

This study investigates both cost-avoidance and improvement in the quality of care and patient outcome attributed to pharmacist intervention in four ambulatory care clinics. Four clinical pharmacists reported 199 interventions made in the pharmacotherapeutic management of 87 ambulatory clinic patients in 1 month. The majority of interventions were based on acceptable professional practices as ranked by peer reviewers. Positive impact of the interventions on patient outcome based on objective and subjective data was documented in 49% of the interventions. Forty-two percent of the interventions improved the process of care with no measurable impact on patient outcome. Cost avoidance was calculated according to interventions made at different steps of the drug use process. Net cost avoidance figures projected to 1 year amounted to $221,056.

Multilevel model to assess appropriateness of pediatric serum drug concentrations.

A multilevel model reviewing four assessment levels for pediatric serum drug concentrations was developed. Criteria for appropriate indication, sample collection, documentation, and utilization were based on therapeutic drug monitoring principles. The model was applied to 222 pediatric serum drug concentrations. Inadequate documentation was a major problem, but it occurred at a lower rate (37%) than previously reported. The rates of inappropriateness for indication (15%), sample collection (16%), and utilization (10%) were well within reported ranges but were significantly lower with pharmacy input. Overall, 48.2% of drug concentrations were inappropriate. Digoxin, phenobarbital, and aminoglycosides had the highest error rates. The annualized cost of inappropriate serum drug concentrations was $12,325. The described method allows for targeting of educational programs with defined areas for improvement. The findings of this study also support the involvement of clinical pharmacists in the therapeutic drug monitoring process.

Patient outcome and the future practice of pharmacy.

The societal move to focus on patient healthcare outcomes as a measure of provider performance is discussed. Recent steps taken by the Joint Commission on Accreditation of Healthcare Organizations to include outcome criteria as part of its accreditation process represent one such example. Pharmacists must define and defend their role in patients' pharmacotherapy in terms of patient outcomes. Collective actions needed by pharmacists are recommended.

Program to improve nurses' knowledge of pediatric emergency medications.

The effects of an educational program designed to improve nurses' knowledge of the use of emergency medications in the pediatric intensive-care unit (PICU) are reported. The clinical pharmacist for a six-bed PICU and a clinical nurse educator developed a program to assess and extend PICU nurses' knowledge of emergency medications with respect to calculations of bolus and continuous infusions, pharmacology, and proper dosage and administration route. The program consisted of a pretest, a pharmacology lecture, calculation problems, a hands-on practicum, and a posttest. Drugs covered were atropine sulfate, sodium bicarbonate, calcium gluconate, calcium chloride, dopamine hydrochloride, dobutamine hydrochloride, epinephrine hydrochloride, isoproterenol hydrochloride, lidocaine hydrochloride, sodium nitroprusside, and norepinephrine bitartrate. A retest was given 13 months after the pretest. The program was completed by 21 nurses over seven months. There was a significant difference between the mean pretest score, 69.5%, and the mean posttest score, 87.3%, due to improvements in scores for the calculation questions. There was no significant difference in the mean time required to complete the pretest and the posttest. A significant correlation was observed between pretest score and months spent practicing in the PICU. Time to take the retest was significantly shorter than the posttest time, and scores continued to improve. An educational program developed cooperatively by pharmacy and nursing improved specific measures of PICU nurses' knowledge of emergency drugs.