Michael E. Pitterle

Health care professional staffing, hospital characteristics, and hospital mortality rates.

To evaluate associations among hospital characteristics, staffing levels of health care professionals, and mortality rates in 3763 United States hospitals, a data base was constructed from the American Hospital Associations Abridged Guide to the Health Care Field and hospital Medicare mortality rates from the Health Care Financing Administration. A multivariate regression analysis controlling for severity of illness was employed to determine the associations. Hospital characteristics associated with lower mortality were occupancy rate and private nonprofit and private for‐profit ownership. Mortality rates decreased as staffing level per occupied bed increased for medical residents, registered nurses, registered pharmacists, medical technologists, and total hospital personnel. Mortality rates increased as staffing level per occupied bed increased for hospital administrators and licensed practical‐vocational nurses. To our knowledge, this is the first study to show that pharmacists were associated with lower mortality rates.

Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability.

UNLABELLED Gabapentin (GBP) is a non-metabolized, non-plasma protein bound, renally excreted antiepileptic drug that is actively absorbed via the system L amino acid transporter. Previous studies have demonstrated that gabapentin displays dose-dependent absorption. OBJECTIVES These studies were conducted to determine inter- and intra-subject variability of gabapentin absorption. Two prospective clinical studies in healthy adult volunteers were conducted. Coefficient of variation (CV) was used to express variability of gabapentin absorption. METHODS Study A: 400-mg single dose, randomized, cross-over study to assess bioavailability of four different gabapentin formulations (n=20, 9 males, 11 females; mean age and weight 41 years, 75.1 kg). Plasma was serially collected up to 48 h and bioavailability (F) calculated post-dose to determine concentration-time curves (AUC). All four formulations were bioequivalent, thus repeated measures analysis was performed to assess inter-and intra-subject variability. Study B: 600-mg single dose study (n=50, 15 males, 35 females; mean age and weight 31.1 years, 72.7 kg) was conducted to determine inter-subject variability in gabapentin F. Urine was collected over 48 h and bioavailability (F) calculated. Urine and plasma gabapentin concentrations were measured by HPLC-UV. RESULTS Study A: Overall mean (CV) of GBP AUC values was 34.1+/-24 ug/h per ml. Inter-subject CV for AUC was 22.5% and intra-subject CV was 12.1%. Study B: Overall mean (SD) GBP F was 49.3+/-13.6%. Inter-subject CV of F was 27.6%. DISCUSSION The inter-subject variability in gabapentin absorption is substantially less than that of the inter-subject variability. This indicates that one would expect a wide range in gabapentin absorption between subjects; however, a much smaller variability within a subject. The within subject variability of gabapentin is small enough that plasma drug monitoring may be used to assess gabapentin absorption for a given subject and the benefit of dose individualization.

Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy

UNLABELLED Gabapentin (GBP) is a non-metabolized antiepileptic drug that is eliminated by renal excretion and displays saturable, dose dependent absorption. The recommended dosing schedule for GBP is t.i.d. At large daily doses, oral bioavailability (F) may be improved by giving the daily dose more frequently. OBJECTIVE To evaluate whether switching GBP dosage regimen from t.i.d. to q.i.d. results in increased oral bioavailability. METHODS This study consisted of two parts; a computer simulated pharmacokinetic model and a clinical pharmacokinetic study in nine adult epileptic patients receiving 3600 mg/day and 11 receiving 4800 mg/day. All patients were evaluated during both t.i.d. and q.i.d. regimens. F were determined by calculation of percent of dose excreted unchanged using steady-state 24-h urine collections and were compared using a paired t-test. RESULTS At 3600 mg/day, mean F following t.i.d. and q.i.d. dosing were 38.7+/-22.1% and 40.0+/-18.9%, respectively (P=0.738). At 4800 mg/day, mean F following t.i.d. and q.i.d. dosing were 29.2+/-16.2% and 35.6+/-17.6%, respectively (P=0.006). DISCUSSION Good agreement was observed between values from this study and predicted values based on the pharmacokinetic model. Improved GBP F at doses of 3600 mg/day was not achieved with more frequent drug administration, and thus is not warranted. At 4800 mg/day, a 22% increase in F was observed with more frequent drug dosing. CONCLUSION GBP F may be significantly increased by q.i.d. versus t.i.d. dosing, depending upon dose level. This increase in F however must be balanced against the inconvenience of more frequent dosing. Therapeutic drug level monitoring may aid in the evaluation of such pharmacokinetic maneuvers.

Diet- and valproate-induced transient hyperammonemia: effect of l-carnitine

Hyperammonemia is an adverse effect of valproate (VPA) treatment. In particular, transient hyperammonemia has been reported to occur in VPA-treated patients after protein-rich meals. This phenomenon may occur secondary to a VPA-mediated carnitine insufficiency. We sought to confirm that protein ingestion would result in transient hyperammonemia and to determine whether supplementation with L-carnitine would prevent this effect. We studied the effect of consumption of a standardized protein-rich meal (45 g protein) before (phase I) and after (phase II) administration of L-carnitine 50 mg/kg/day for 7 days in 11 epileptic children (13.3 +/- 2.3 years of age) receiving VPA. Venous blood was obtained during fasting (baseline) and at 2 and 4 hours after the protein-rich meal for analysis of ammonia (NH3), and VPA concentrations. Mean VPA trough concentrations did not differ significantly at any time. After protein ingestion, 2-hour NH3 concentration increased by 86% (P < .05) from baseline in phase I as compared with a 38% increase in phase II. In both phases I and II, 4-hour NH3 concentrations decreased toward baseline values. We conclude that (1) modest protein ingestion can result in significant transient increases in NH3 in VPA-treated children, (2) significant increases may occur in patients with normal fasting NH3 concentrations, (3) these increases can be significantly attenuated by L-carnitine supplementation, and (4) these changes do not appear to be related to changes in VPA concentration.

Hospital and pharmacy characteristics associated with mortality rates in United States hospitals

We attempted to determine hospital and pharmacy characteristics associated with mortality rates in 4864 United States hospitals. Data were obtained from the Health Care Financing Administration, the American Hospital Association, and the National Clinical Pharmacy Services survey. Univariate and multivariate regression models were used to determine which hospital characteristics were associated with mortality. A similar regression analysis was performed on 718 hospitals for which detailed pharmacy information was available. In a multivariate regression model, some characteristics of 4864 hospitals associated with reduced mortality rates were high‐technology index (R2=0.09, p<0.001), severity of illness (R2=0.048, p<0.001), number of hospital beds (R2=0.016, p<0.001), and medical personnel (R2=0.012, p<0.001). This analysis accounted for 41% of the mortality rate variance. For the 718 hospitals and pharmacies, some of these characteristics were high‐technology index (R2=0.157, p<0.001), severity of illness (R2=0.07, p<0.001), number of pharmacists/average daily census (R2=0.021, p<0.001), and combined hospitalwide clinical pharmacy services (R2=0.016, p<0.01). The results of this analysis were similar to those in the only other large study in this area, but that excluded pharmacy characteristics. This is the first study to show a statistically significant association between pharmacist and pharmacy variables and reduced hospital mortality rates.

Staffing and the Cost of Clinical and Hospital Pharmacy Services in United States Hospitals

A survey was mailed to pharmacy directors at all United States acute care medical‐surgical hospitals that related to staffing and cost components of hospital pharmacies and clinical services. Cost information was evaluated as both unadjusted and adjusted for severity of illness using the Health Care Financing Administrations Medicare case mix index (CMI). Unadjusted drug costs/occupied bed/year were

Relationship between valproic acid dosage, plasma concentration and clearance in adult monotherapy patients with epilepsy.

13,350 ± 6927, a 36% increase over 1992 and a 112% increase over 1989, with statistically significant differences observed by geographic region, hospital size, hospital ownership, and drug delivery system. Annual median pharmacist salary costs/patient associated with centrally based clinical pharmacy services were drug use evaluation

Effect of lamotrigine on carbamazepine epoxide/carbamazepine serum concentration ratios in adult patients with epilepsy

111, in‐service education

Evaluation of Carbamazepine and Carbamazepine-Epoxide Protein Binding in Patients Undergoing Epilepsy Surgery

20, drug information

An Assessment of Recent Pharmacy Graduates' Knowledge and Competency, Professional Practice Functions, and Involvement in Pharmacy Teaching Programs

117, poison information