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Biomedical subjects

J T DiPiro

Publications and source records attributed to J T DiPiro.

At least 19 recordsLinked to original sources

Efficacy of a single intravenous dose of amphotericin B for Candida urinary tract infections: further favorable experience.

Studies in experimental animals and humans have shown that Amphotericin B (AmB) persists in urine for days to weeks after a single IV dose in levels that should inhibit candidal organisms and thereby obviate the need for frequent dosing. Including data from four previously described patients, we have now treated a total of 11 patients (12 episodes) with Candida urinary tract infections with single-dose AmB (six, Candida albicans; two, C. tropicalis; four, other nonalbicans Candida). The duration of candiduria prior to entry ranged from 18 to 180 days. Predisposing conditions included renal transplantation (1), diabetes mellitus (8), genitourinary stones (1) or anomalies (4), catheterization (2), and antibacterial therapy (11). A single patient was intolerant of AmB. Out of 11 evaluable candiduric episodes, eight resolved. Failure occurred in one patient with a chronic indwelling bladder catheter and in the allograft recipient. The data suggest that the sustained urinary excretion of AmB may permit successful single- or paucidose therapy of Candida urinary tract infections in some patients with a minimum of toxicity.

Adult↗

Impact of clinical pharmacy services on renal transplant patients' compliance with immunosuppressive medications.

BACKGROUND: Non-compliance with immunosuppressive medications may result in allograft rejection and is regarded as an important impediment to post-transplant care. This randomized, controlled trial evaluates the impact of clinical pharmacy services on renal transplant patients' compliance with immunosuppressive agents. METHODS: Patients who received a renal transplant at the Medical College of Georgia from February 1997 through January 1999 were randomized in the intervention or control group provided they met study criteria. In addition to routine clinic services at each clinic visit, patients in the intervention group received clinical pharmacy services, which included medication histories and review of patients' medications with an emphasis on optimizing medication therapy to achieve desired outcomes and minimizing adverse medication events. The clinical pharmacist also provided recommendations to the nephrologists with the goal of achieving desired outcomes. To promote medication compliance by using compliance enhancement strategies, the clinical pharmacist counseled patients concerning their medication therapy and instructed them how to properly take their medications. Patients in the control group received the same routine clinic services as the intervention group except that they did not have any clinical pharmacist interaction. Compliance rate (CR) was calculated and patient's compliance status was determined from the CR. The CR, the fraction of patients remaining compliant for each month, and the mean time patients were compliant were compared between groups. Whether there was a difference in the frequency of patients achieving 'target' immunosuppressive levels in the control and study groups was evaluated. RESULTS: The mean CR for patients who had clinical pharmacist intervention (n=12) was statistically higher than the control group's (n=12) mean CR (p<0.001). During the 12-month post-transplant study period, patients in the intervention group had a longer duration of compliance than patients in the control group (p<0.05). Additionally, patients who had clinical pharmacy services had a greater achievement of 'target' levels than patients who did not receive these services (p<0.05). CONCLUSIONS: Patients who received clinical pharmacy services with traditional patient care services had better compliance with immunosuppressants than patients who only received traditional patient care services. Results of this study suggest a multidisciplinary team that includes a clinical pharmacist as part of the care for post-transplant patients is beneficial for enhancing medication compliance.

Chi-Square Distribution↗

Renal transplant patient compliance with free immunosuppressive medications.

BACKGROUND: Noncompliance with immunosuppressive medications after renal transplantation is believed to be a major cause of allograft rejection and graft loss, with the impressive costs of these agents considered a significant reason for noncompliance. Our purpose was to determine the compliance rates of renal transplant patients who received their immunosuppressant therapy free of charge and evaluate their patterns of compliance. METHODS: All patients who received a renal transplant and received their immunosuppressant medications at our institution for their first year posttransplant were included in the study. Compliance rate was calculated and serum immunosuppressant concentrations were obtained to validate compliance assessments. RESULTS: Eighteen patients were included in the study. Approximately 48% of noncompliant patients were found to have subtarget drug concentrations, although only 14% of compliant patients had subtarget levels (chi2=12.9, P<0.001). At 5 months posttransplant, 95% of the patients remained compliant; however, by 12 months posttransplant, only 48% of the patients remained compliant. The mean time to the first noncompliant month was 9.8 months (95% confidence intervals=8.60-11.0). CONCLUSIONS: Patients who received their immunosuppressants free of charge were generally compliant within their first year of transplantation, however, compliance tended to decrease over time. This suggests that drug cost alone does not explain noncompliant behavior. Intensive efforts to increase medication compliance before month 8 posttransplantation should be implemented.

Adult↗

Medication assistance programs for uninsured and indigent patients.

Pharmaceutical company-sponsored medication assistance programs and the pharmacist's role in obtaining medications for indigent patients are discussed. Information about enrolling in medication assistance programs can be obtained through a variety of sources, including the Internet. Although some eligibility criteria may be common to many programs, each company operates independently, and the eligibility criteria vary, individuals involved in the administration of medication assistance programs should strive to ensure that correct information is reported. Pharmacists can play an important role in acquiring medications for patients by reviewing patient information, recommending patients for enrollment, and serving as a liaison between the patient or health care provider and the program administrator. Many pharmaceutical companies have programs that provide prescription medications to indigent or uninsured patients. Pharmacists can serve as a liaison between these programs and the patient or the health care provider.

Drug Industry↗

Assistance programs available for medications commonly used in transplant patients.

Pharmaceutical manufacturers have programs available to supply medications to indigent patients at little or no cost. Enrolling needy patients into these programs should increase patient compliance to medications, minimize patient and institution financial burdens, and decrease adverse events associated with medication noncompliance. However, access to assistance programs by patients in need is limited if physicians and other health care providers are unaware of the existence of such programs or not informed of each program's enrollment process. The literature is void of a manuscript describing assistance programs available for commonly prescribed medications used in transplant patients. This article offers a concise summary of medication assistance programs available through the pharmaceutical industry to assist in the procurement of medications that are commonly prescribed for the transplant population, including immunosuppressants, antibacterials, gastrointestinal, cardiovascular, and hypoglycemic agents. This article should be used by health care professionals as a guide to the availability and requirements of medication assistance programs.

Anti-Bacterial Agents↗

Cost-benefit analysis of a clinical pharmacist-managed medication assistance program in a renal transplant clinic.

UNLABELLED: Medicare pays for 80% of the cost of immunosuppressant agents needed within the first 3 years of solid organ transplantation; however, many patients cannot afford the remaining 20%. Furthermore, many patients who are beyond 3 years post-transplantation and have prescription coverage cannot afford the co-payment for these medications. Other patients may not be able to afford their medications due to limited or no insurance coverage. The Medical College of Georgia (MCG) has been giving immunosuppressant medications to renal transplant patients if they cannot afford to pay for them. To assist MCG with drug cost for medications and maintain quality care for renal transplant patients, a clinical pharmacist-managed medication assistance program was implemented to procure immunosuppressants from pharmaceutical manufacturers. METHODS: All patients enrolled in medication assistance programs from 1 January 1998 through 31 December 1998 were included in this analysis. Medication acquisition costs with and without Medicare reimbursement and the cost of implementing the clinical pharmacist-managed medication assistance program were used to determine the value of implementing this service. RESULTS: Sixty-one patients were enrolled in manufacturers' assistance programs and a net cost avoidance of $124,793 was realized for the year of the program (benefit-to-cost ratio of 7.5:1). Assuming that the hospital collected the maximum amount allowed for patients receiving Medicare benefits, a cost avoidance of $69,233 was calculated (benefit-to-cost ratio of 4.16:1). CONCLUSIONS: A clinical pharmacist-managed medication assistance program in a renal transplant clinic produced substantial cost savings over this 1-year study period. For each dollar spent in pharmacist's time, a minimum of $4 was returned to the institution.

Cost-Benefit Analysis↗

Short-term prophylaxis in clean-contaminated surgery.

Postoperative infections are not consistently controlled by current practice measures. From a recent study of 12,384 patients, postoperative infection occurred in 22% of colorectal procedures and 25% of upper gastrointestinal procedures. Infections were associated with a higher death rate, longer hospitalization, and more intense post-discharge care. Control of infections for clean-contaminated procedures requires effective bowel cleansing when appropriate, meticulous surgical technique, and timely antimicrobial administration. Many patients undergoing clean-contaminated surgery do not receive properly timed antimicrobials. Although the comparative value of oral (neomycin and erythromycin) or parenteral antimicrobials for colon surgery remains an unresolved issue, the combination can be beneficial for many colorectal operations. Third generation cephalosporins are not consistently more effective than older agents such as cefoxitin and increase bacterial resistance. Improper antimicrobial timing is one of the most common problems with surgical prophylaxis and is fully under the control of the surgeon. To maximize benefits of antimicrobial prophylaxis, systems should be devised to assure timely administration.

Antibiotic Prophylaxis↗

Infection in surgical patients: effects on mortality, hospitalization, and postdischarge care.

In-hospital mortality, length of stay (LOS), and level of postdischarge care in infected and noninfected surgical patients were studied. An analysis was conducted of a database that included diagnostic, procedure, and drug data collected when surgical patients were discharged from the hospital. Hospitals consisted of 90 nongovernment, nonspecialty, teaching, and nonteaching acute care hospitals of more than 100 beds. Patients in the database included 288,906 patients of all ages hospitalized between July and September 1994. Patients selected of those who had undergone procedures likely to pose a moderate to high risk of infection. Of the 288,906 patients, 12,384 had undergone a moderate- to high-risk procedure; of these, 1,479 (11.9%) had had an infection during their hospitalization. Infection rates ranged from 1.9% to 25.4%, depending on the procedure. The in-hospital mortality rate in infected patients was 14.5%, versus 1.8% for noninfected patients. Similarly, LOS in infected patients (median, 14 days) was substantially greater than in noninfected patients (4 days). About 24% of infected patients required additional professional care after discharge, compared with 7% of noninfected patients. Infection occurs in a substantial portion of surgical patients and is associated with a higher death rate, longer hospitalization, and more intense postdischarge care.

Hospitalization↗

Capillary electrophoresis for therapeutic drug monitoring.

Therapeutic drug monitoring is commonly used in both the ambulatory and hospital patient care settings. Routine measurement of concentrations of therapeutic agents in biological fluids is critical for certain drugs to maintain therapeutic benefit with minimizing drug-associated toxicities. Many analytical laboratory techniques are currently available to measure drug concentrations in biological samples. Recently there has been an increased interest in the use of capillary electrophoresis (CE) for measuring concentrations of therapeutic drugs in patient samples. However, while there are numerous reports of CE being used to measure drug concentrations in solution and pharmaceutical dosage forms, there are relatively few reports of the use of CE for measuring therapeutic agents in patient samples. The purpose of this paper is to provide an overview of methods currently used to measure therapeutic drugs in patient samples along with possible future trends for the use of CE in therapeutic drug monitoring.

Drug Monitoring↗

Immunoglobulin E and eosinophil counts are increased after sepsis in trauma patients.

OBJECTIVES: To determine the time course of plasma immunoglobulin E (IgE) concentration increases after traumatic injury, if increased IgE concentrations were related to clinical events or complications, and if increased peripheral eosinophil counts could be related to trauma, sepsis, or organ-specific complications. DESIGN: Data relating to severity of injury, clinical complications, plasma concentrations of IgE, and peripheral eosinophil counts were prospectively collected. SETTING: Trauma service, tertiary-care medical center. PATIENTS: One hundred adult trauma patients admitted to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma IgE concentrations increased in most patients. However, the greatest increases were observed in patients with sepsis (p = .03), renal dysfunction (p = .04), or pneumonia (p = .02). IgE increases were not related to severity or mechanism of injury, allergy history, or age. The day of highest observed IgE concentration was related to the day of onset of sepsis (p = .012, r = .39), and occurred a mean of 3.8 days after sepsis. Most patients had increased peripheral eosinophil counts and eosinophil percentages of white blood cells during their intensive care unit stays. Eosinophil counts were greater in patients with sepsis (p < .0001), severe sepsis (p < .0001), or pneumonia (p < .002). CONCLUSIONS: Increased IgE concentrations and eosinophil counts were found after sepsis and do not appear to be related to the initial injury. Since IgE and eosinophil production are enhanced by interleukin-4 and interleukin-5, respectively, these findings suggest that T-helper lymphocyte type 2 cytokines are activated in response to sepsis after traumatic injury.

Adolescent↗

Heparin versus citrate regional anticoagulation during autotransfusion in a porcine intra-abdominal hemorrhage model.

Our objective was to determine the effects of anticoagulants and blood loss on hemodynamic, hematologic, and coagulation parameters following autotransfusion in an animal model of intraabdominal hemorrhage. We performed a prospective, randomized observational animal study at an animal research laboratory at a university medical center. Eight Landrace, domestic pigs, weighing 17-23 kg, each underwent jugular venous and iliac arterial catheterization and laparotomy with retroperitoneal dissection for aortic exposure to simulate an operative environment. Following baseline laboratory and hemodynamic determinations, intra-abdominal hemorrhage was accomplished via aortotomy in three sequential 10 mL/kg blood volumes. After allowing pooling in the exposed retroperitoneum to ensure tissue contact, the shed blood was suctioned, processed, and washed in an autotransfusion device utilizing either heparin (n = 4) or acid-citrate-dextrose (n = 4) as a system anticoagulant. Prior to autologous transfusion, each pig received a 20 mL/kg intravenous bolus of 0.9 per cent saline to treat shock. The processed blood was then infused, and laboratory and hemodynamic measurements were repeated following each cycle of hemorrhage and autotransfusion. Sequential fixed volume hemorrhage resulted in significant reductions in mean arterial pressure. Despite crystalloid infusion and transfusion of processed shed blood, postresuscitation mean arterial pressure did not return to baseline values, with no difference noted between anticoagulant groups. Infusion of increasing volumes of autologous blood resulted in significant reductions in hematocrit, platelet count, fibrinogen, antithrombin III, ionized calcium, and total protein. The decrease in concentration of each variable was independent of the choice of anticoagulant with the exception of antithrombin III, with higher levels noted in animals receiving blood anticoagulated with acid-citrate-dextrose. Prothrombin time and partial thromboplastin time were unaffected by volume of autologous transfusion or choice of anticoagulant. We conclude that changes in hemodynamic, hematologic, and coagulation parameters associated with hemorrhage and autotransfusion appear related more to the volume of blood loss and the cumulative pheresis of plasma than to the choice of anticoagulant.

Animals↗

Pharmacodynamics of antimicrobial therapy in surgery.

INTRODUCTION: "Pharmacodynamics" refers to the relationship of drug concentrations in serum or tissues to effects on biologic systems. Concepts used to describe antimicrobial pharmacodynamics include the minimal inhibitory concentration (MIC), the minimal bactericidal concentration (MBC), and serum bactericidal titers (SBT), as well as post-antibiotic effect. METHODS: Pertinent published literature was identified through a MEDLINE search. RESULTS: Aminoglycosides have a concentration-dependent effect on bacteria killing and possess a relatively long postantibiotic effect. Given these characteristics, single-daily dosing, where the total daily dose with a traditional aminoglycoside regimen is given as one dose, may be more efficacious compared with more frequent dosing. For beta-lactam antimicrobials, bacterial killing is related to the duration of time that the free drug concentration exceeds the bacterial MIC. Beta-lactam antimicrobials have been shown to have no, or a short postantibiotic effect. Beta-lactam antimicrobials may be more effective when administered as continuous intravenous infusions. CONCLUSIONS: Pharmacodynamic variation may result from differences in drug sensitivity among individuals and the nature of the interaction between antimicrobials and microorganisms. Proper use of pharmacokinetic and pharmacodynamic principles can result in more effective and less toxic antimicrobial regimens.

Aminoglycosides↗

Pharmacokinetics of reconstituted human high-density lipoprotein in pigs after hemorrhagic shock with resuscitation.

OBJECTIVES: Reconstituted human high-density lipoprotein (HDL) can inhibit lipopolysaccharide effects in vivo. The major objectives of this study were to characterize the pharmacokinetics of reconstituted HDL in a stressed large-animal model and to provide preclinical tolerance information in support of use of reconstituted HDL in humans. DESIGN: A randomized, blinded, placebo-controlled trial where each animal received either reconstituted human HDL at a dose of 100 mg/kg (apolipoprotein A-I) or placebo, immediately after hemorrhagic shock and resuscitation. SETTING: Animal laboratory. SUBJECTS: Twelve immature female swine (18 to 25 kg) were studied. INTERVENTIONS: Six to 8 days before shock and study drug administration, animals were anesthesized and catheters were placed in the external jugular vein and abdominal aorta. These catheters were secured to the dorsal surface. On the day of shock, the animals were sedated (alpha-chloralose) and 50 mL/kg of arterial blood was removed over 0.5 hr. One half hour after blood removal, shed blood was infused, which was immediately followed by study drug (reconstituted HDL or placebo), and then by 1 L of lactated Ringer's solution. MEASUREMENTS AND MAIN RESULTS: Physiologic (arterial blood pressure, heart rate, respiratory rate) and laboratory (serum chemistries, hematologic and coagulation studies, and blood gases) measurements were determined intermittently for 96 hrs after the induction of shock. Blood was collected intermittently for 48 hrs after shock for assay of apolipoprotein A-I and phosphatidylcholine in plasma. Reconstituted HDL was well tolerated and did not appear to alter the physiologic responses to shock and resuscitation. HDL transient increase in aspartate aminotransferase concentration was noted in the reconstituted group but this increase normalized by 24 hrs after drug administration. Mean apolipoprotein A-I pharmacokinetic parameters were as follows: half-life 24.5+/-5.3 (SD) hrs; clearance 41.9+/-10 mL/hr; and volume of distribution 1.39+/-0.08 L. The apparent mean half-life of phosphatidylcholine was 5.4+/-0.8 hrs. CONCLUSIONS: Reconstituted human HDL was well tolerated in animals that had undergone hemorrhagic shock with resuscitation. The apolipoprotein component of reconstituted HDL had a relatively long half-life, with distribution limited to the vascular space. These findings support the investigational use of this product in humans.

Analysis of Variance↗

Interleukin-10 is associated with the development of sepsis in trauma patients.

Interleukin-10 (IL-10) is a potent regulator of proinflammatory cytokines, including tumor necrosis factor-alpha, IL-1, IL-6, and interferon-gamma. We retrospectively evaluated 66 severely injured patients for detectable plasma IL-10. the presence or absence of IL-10 was correlated with clinical parameters. Forty of 66 patients had detectable levels of IL-10. Plasma IL-10 was associated with admission hypotension (p < 0.01) and the development of sepsis (p < 0.05). There was no difference between IL-10-positive and -negative patients with respect to age, mechanism or severity of injury, blood transfusion, operative interventions, or the subsequent development of ARDS, hepatic dysfunction, or renal insufficiency. We conclude that IL-10 can be detected in the plasma of some severely injured patients and that it is associated with the development of sepsis. Further investigation of the immunoregulatory effects of IL-10 after trauma is indicated.

Adult↗