bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Heat Treatment of Potentially Infected Blood Samples on Therapeutic Drug Monitoring of Selected Drugs
Authors: Burger David M. , van Dijk Elisabeth A. , van Gijn Roel , Beijnen Jos H.
Published: January 2017

OBJECTIVE:

To investigate the effect of heat treatment on the outcome of drug analysis in whole blood and serum for eight drugs routinely assayed for therapeutic monitoring.

DESIGN:

All blood and serum samples (n=373) received at the pharmacy laboratory for therapeutic monitoring of carbamazepine, digoxin, gentamicin, kanamycin, phenobarbital, phenytoin, theophylline, and valproic acid were heated at 60°C for 30 minutes. Serum was subsequently assayed by fluorescence polarization immunoassay (TDx).

SETTING:

The study was conducted at the analytical laboratory of the pharmacy, using standard laboratory procedures.

MAIN OUTCOME MEASURES:

Analyses of heated samples were compared with analyses of untreated samples using a paired Wilcoxon signed-rank test.

RESULTS:

Serum concentrations of phenytoin from treated whole blood, and of gentamicin in treated serum, were significantly lower than in untreated samples. These differences, however, were small, clinically irrelevant, and lie within assay variation intervals. Heat treatment did not influence the outcome of analyses for carbamazepine, digoxin, kanamycin, phenobarbital, theophylline, and valproic acid.

CONCLUSIONS:

Heat treatment of whole blood and serum samples of the investigated drugs does not influence the outcome of drug analysis, although drug instability cannot be fully excluded. Heat treatment can protect laboratory technicians from HIV infection without influencing therapeutic monitoring of these drugs.
Current Issues Surrounding Women and Minorities in Drug Trials
Authors: Wermeling Daniel P. , Selwitz Ada Sue
Published: January 2017

OBJECTIVE:

Our principal objective is to make readers aware of conflicting demands placed on investigators and the pharmaceutical industry regarding inclusion of women and minorities in clinical research. Tremendous pressures have been placed to expedite the drug approval process. Moreover, during the last decade certain segments of society, particularly women and minorities, have demanded greater participation in clinical drug trials and earlier access to investigational drug therapies. Regulations that have served the clinical research community (pharmaceutical industry, investigators, institutional review boards) as guidelines for safe conduct of human clinical trials are being challenged by social and political change. This article provides an overview of some of the controversy relative to federal regulations governing clinical trials; scientific concerns; social, political and legal trends; and ethical principles applied to human clinical research.

DATA SOURCES:

Literature for this paper was retrieved from a variety of sources including the nonmedical press, editorials, peer-reviewed journals, Department of Health and Human Services regulations, National Institutes of Health policy, the Belmont Report, and regulations of the Food and Drug Administration.

DATA SYNTHESIS:

Scientists evaluating new therapeutic agents ask specific research questions to assess safety, efficacy, and the mechanism(s) of action. Because of concerns for scientific validity, safety, liability, and convenience, many early evaluations of new drugs involve patient populations that may not represent the ultimate users of a new drug. Federal regulations and ethical principles allow certain groups of people to be excluded from early research proposals because they are thought to be putting themselves at greater risk by participating than are other groups. However, women, minorities, and other populations are demanding greater access to investigational drugs. The focus has changed from protection from research risks and burdens to the potential benefits a person or class of people may obtain by participating in a study.

CONCLUSIONS:

Scientists, the pharmaceutical industry, regulators, and society must agree on a safe and efficient mechanism for new drug development that permits more equitable participation of subjects in the various phases of research.
Assessment of Patient Acceptance and Inhalation Technique of a Pressurized Aerosol Inhaler and Two Breath-Actuated Devices
Authors: Nimmo Cindy J. Reesor , Chen Daniel N.M. , Martinusen Shelagh M. , Ustad Tina L. , Ostrow David N.
Published: January 2017

OBJECTIVE:

To assess inhalation technique in patients after written instruction alone, written and verbal instruction, and clinical use of two new inhalation devices.

DESIGN:

Randomized, crossover evaluation of the albuterol Diskhaler and the terbutaline Turbuhaler.

SETTING:

Canadian tertiary-care hospital.

PATIENTS:

Twenty hospitalized adults with asthma or chronic obstructive pulmonary disease currently using an albuterol metered-dose inhaler (MDI). Nineteen patients received Diskhaler, 16 received Turbuhaler, 15 received both inhalers, and 10 patients used both inhalers for three days each.

INTERVENTIONS:

Patients were randomized to receive either Diskhaler or Turbuhaler for three days. Inhaler technique was assessed after written instruction, written plus verbal instruction, at the first scheduled dose after instruction, and after three days of clinical use. Patients remaining in the hospital after three days crossed over to the other study inhaler and the same protocol was followed.

MAIN OUTCOME MEASURES:

Patient inhalation technique was assessed and compared for the MDI, Diskhaler, and Turbuhaler.

RESULTS:

Assessment of MDI technique revealed that 35 percent of patients used their MDI correctly on the first puff, and 42 percent used it correctly on the second puff. Following written instruction alone, correct technique was demonstrated by 32 percent of patients with Diskhaler and 6 percent with Turbuhaler. Technique significantly improved following verbal instruction, although 40 percent of the patients required up to three attempts to demonstrate correct technique on at least one of the study inhalers. After three days of clinical use, correct technique was demonstrated in only 54 percent of the Diskhaler and 64 percent of the Turbuhaler assessments. Performance at this assessment was, however, significantly better on the Turbuhaler than on the MDI (p=0.01). Performance on the Diskhaler was not significantly different from the performance on the other inhalers.

CONCLUSIONS:

Written instruction alone is inadequate in teaching correct inhalation technique. Verbal instruction and technique assessment are essential for patients to achieve proper technique. Patients may perform better on the Turbuhaler than on other inhalation devices.
Computerized Monitoring Protocols as a Pharmaceutical Care Practice Enhancement: A Conceptual Illustration Using Diabetes Mellitus
Authors: Boyd Alan F. , Hartzema Abraham G.
Published: January 2017

OBJECTIVE:

To illustrate how a computer system used in an ambulatory care pharmacy setting might enhance care of patients with diabetes by prospectively monitoring and prompting them to seek routine medical care.

DATA SOURCES:

A MEDLINE search to identify existing works on informatics was conducted. An epidemiology and general medical literature review of diabetes mellitus was also performed via MEDLINE. Additionally, known textbooks on the disease were consulted.

CONCLUSIONS:

Programming a computer system to prompt pharmacists to remind their patients of necessary medical interventions could save medical resources by warning chronically ill patients not to ignore routine medical care. Also, this would allow the pharmacist to prospectively monitor patient outcomes. By knowing when medical interventions are due and obtaining feedback from patients on the results of the medical contact, pharmacists increase their knowledge about patient outcomes and the rationale behind changes in pharmacotherapy. It is expected that such a system would prevent the inconspicuous development of chronic complications.
Nasal Absorption of Growth Hormone in Normal Subjects: Studies with Four Different Formulations
Authors: Laursen Torben , Ovesen Per , Grandjean Birgitte , Jensen Sigrid , Jørgensen Jens Otto L. , Illum Peter , Christiansen Jens Sandahl
Published: January 2017

OBJECTIVE:

Current growth hormone (GH) therapy with daily subcutaneous injections results in elevated serum concentrations of GH lasting for several hours, whereas physiologic GH secretion is characterized by a short-duration peak and low basal concentrations. A closer imitation of this pattern might be achieved by administering GH nasally. We studied the effect on the absorption of nasally administered human GH of increasing concentrations of the enhancer didecanoyl-L-α-phosphatidylcholine (DDPC).

DESIGN:

Four formulations of nasal GH containing the enhancer DDPC in the relative concentrations 0, 4,8, and 16% w/w were administered in random order.

SETTING:

Participants were admitted to the hospital during the four study periods.

INTERVENTIONS:

On four occasions the subjects received GH 6 IU (2 mg) in each nostril. Blood was sampled frequently for four hours. Anterior rhinoscopy was performed at 0 and 4 h. During the study the subjects completed a questionnaire to record nasal symptoms.

PATIENTS:

Sixteen healthy subjects were examined at 0800 h after an overnight fast.

MAIN OUTCOME MEASURES:

Bioavailability of a nasal preparation of human GH: area under the curve (AUC), the maximum concentration(Cmax), and the time to reach maximum concentration (tmax). Scores for each nasal symptom were recorded as were the total scores.

RESULTS:

AUC, Cmax, and tmax,. were not significantly affected by increasing the DDPC concentration from 0 to 4 percent or from 8 to 16 percent. AUC and Cmax, however, increased significantly when the concentration of DDPC was changed from 4 to 8 percent. Mean (±SD) AUC (μg·h/L) increased from 20.51 ± 10.53(4 percent)to 46.14 ± 34.59 (8 percent), (p<0.005). Mean (±SD) of Cmax (μg.L) increased from 11.11 ± 5.02 (4 percent) to 28.22 ± 20.85 (8 percent), (p=0.OO2). Mean (±SD) of tmax (min) was not significantly different on the four occasions(range 40.6 ± 36.4 to 61.0 ± 45.2 min, p=0.13). The symptom scores (range 17.56–21.5, maximum 360) were not significantly different (p=0.59).

CONCLUSIONS:

Increasing the relative concentration of the enhancer DDPC increases the absorption of nasally administered GH.
Pharmacy-Perceived Barriers to Cancer Pain Control: Results of the North Carolina Cancer Pain Initiative Pharmacist Survey
Authors: Krick Stacie E. , Lindley Celeste M. , Bennett Michelle
Published: January 2017

OBJECTIVE:

To assess pharmacists' knowledge, attitudes, and beliefs regarding the use of narcotics in cancer pain management, identify pharmacist counseling activities for cancer pain patients, assess pharmacy-related barriers to cancer pain management, and evaluate the availability of narcotic analgesics.

METHODS:

Mailing of a six-page survey.

SETTING:

Five hundred randomly selected pharmacists registered in North Carolina.

PARTICIPANTS:

Of 500 pharmacists surveyed, 141 surveys were completed and returned for a response rate of 28.2 percent.

RESULTS:

Pharmacists surveyed were knowledgeable regarding the problem of undertreatment of cancer pain. More than 80 percent of respondents replied that most cancer patients experience pain at some time during their illness. Eighty-five percent of respondents agreed that the nurse must believe the patient's report of pain and that the patient is the best judge of the intensity of the pain. Conservative physician prescribing patterns and conservative administration patterns of nurses were identified as perceived barriers to adequate pain management by 51 and 44 percent of respondents, respectively. Less than 30 percent of respondents frequently counseled cancer pain patients and were unable to identify patients who have cancer pain as a major medical illness. Hospital pharmacists recommended adjunctive therapy more often than did community pharmacists (p=0.013). Interventions in pain management regimens were more often conducted by hospital pharmacists than by community pharmacists (p=0.049). Differences in availability of narcotics was noted among practice sites for some more potent narcotics. Of the pharmacists surveyed, only 43 percent had attended a continuing education program on cancer pain management. Ninety-six percent of respondents were interested in attending a continuing education program in the future.

CONCLUSIONS:

Pharmacists in North Carolina are aware that the undertreatment of cancer pain is a serious medical problem. Unfortunately, pharmacists appear to be unable to identify patients with cancer pain as a major medical problem; therefore, counseling activity is limited. Addiction is still perceived as a barrier by some pharmacists. Through organizations such as the North Carolina Pain Initiative, these problems can be addressed.
Mathematical Examination of Dual Individualization Principles (II): The Rate of Bacterial Eradication at the Same Area under the Inhibitory Curve is More Rapid for Ciprofloxacin Than for Cefmenoxime
Authors: Goss Thomas F. , Forrest Alan , Nix David E. , Ballow Charles H. , Birmingham Mary C. , Cumbo Thomas J. , Schentag Jerome J.
Published: January 2017

OBJECTIVE:

To compare two antibiotics at equal ranges of area under the inhibitory curve (AUIC) exposure to determine if the rate of bacterial eradication differed between these antibiotics.

DESIGN:

Retrospective comparison of two previously collected studies of similar patients with nosocomial pneumonia.

SETTING:

Hospitalized patients, most intubated in critical care units with nosocomial pneumonia.

PARTICIPANTS:

Patients treated with either iv ciprofloxacin (n=74) or the iv third-generation cephalosporin cefmenoxime (n=43) were compared for their length of treatment required to eradicate bacterial pathogens from their respective infection sites, using serial cultures from the site of infection. All patients were also assessed for clinical outcomes. Serum samples were obtained to evaluate individual patient antibiotic pharmacokinetics, which were used to model pharmacodynamics of response. The HPLC assay used for each antibiotic had interday coefficients of variation <10 percent. Serum concentration versus time profiles were fit using the computer program ADAPT II to determine pharmacokinetic parameters for each patient. The primary drug exposure measure that related to response was the AUIC, calculated as steady-state AUC0–24/minimum inhibitory concentration.

RESULTS:

AUIC values in the patients ranged from 6.0 to more than 7000, yet the AUIC value was highly predictive of time to bacterial eradication (p<0.OO 1). Although more than 75 percent of patients eventually achieved eradication of pathogens from tracheal aspirate cultures, ciprofloxacin and cefmenoxime differed significantly in the time required to sterilize these cultures. At appropriate AUIC values (>250) for ciprofloxacin, the median time to eradication was two days, while cefmenoxime (also at AUIC values >250) required six days to achieve the same result.

CONCLUSIONS:

We conclude that the more rapid in vitro bacterial killing, which is characteristic of ciprofloxacin at optimal AUIC values, can manifest in vivo as more rapid clearance of bacteria from the respiratory tract of patients, even when both agents are controlled for initial antibacterial exposure (i.e., same AUIC).
Concurrent Use of Foscarnet and Ciprofloxacin May Increase the Propensity for Seizures
Authors: Fan-Havard Patty , Sanchorawala Vaishali , Oh Julee , Moser Eileen M. , Smith Stephen P.
Published: January 2017

OBJECTIVE:

To report a possible interaction between foscarnet and ciprofloxacin in two patients with AIDS, cytomegalovirus (CMV) retinitis, and disseminated Mycobacterium avium complex (MAC) infection and to review the available literature related to foscarnet associated seizures.

DATA SOURCE:

Case report information was obtained from Medical Service Daily Rounds during the patients' hospitalization and from the patients' medical records. Computerized (MEDLINE) and manual ( Index Medicus) search methods were used to obtain English-language literature published between 1980 and 1993.

DATA SYNTHESIS:

Foscarnet is a synthetic antiviral agent with activity against herpes viruses and HIV. The incidence of seizures with foscarnet infusion is high, ranging from 13 to 15 percent. Predisposing factors such as renal impairment, electrolyte and metabolic abnormalities, and underlying neurologic disorders have been associated with seizures during foscarnet therapy. We describe two patients with AIDS who developed generalized tonic-clonic seizures while receiving foscarnet and ciprofloxacin for the treatment of CMV retinitis and disseminated MAC infection, respectively. Neither of the patients had any of the aforementioned risk factors for foscarnet-associated seizures.

CONCLUSIONS:

Concurrent administration of ciprofloxacin, a known epileptogenic agent, and foscarnet may predispose patients to the development of seizures.
Indomethacin-Induced Colonic Ulceration and Bleeding
Authors: Oren Ran , Ligumsky Moshe
Published: January 2017

OBJECTIVE:

To report a case of nonsteroidal antiinflammatory drug (NSAID)-induced lower gastrointestinal (GI) bleeding.

CASE SUMMARY:

A patient in whom short-term ingestion of indomethacin was associated with colonic ulceration and significant gastrointestinal bleeding is described.

DISCUSSION:

The bleeding ulceration of the ascending colon, associated in our patient with short-term indomethacin intake, confirms previous reports of the drug's deleterious effect on the lower GI tract. The incidence of NSAID injury of the small intestinal colon may be higher than that previously reported.

CONCLUSIONS:

A prospective study of NSAID users could assess the magnitude of lower GI lesions, concomitant with upper GI evaluation, and help determine limitations in the use of this drug class.
Misadventures with Activated Charcoal and Recommendations for Safe Use
Authors: Mauro Laurie S. , Nawarskas James J. , Mauro Vincent F.
Published: January 2017

OBJECTIVE:

To review published reports of adverse effects associated with single- and multiple-dose activated charcoal therapy, and to formulate recommendations for safe use of activated charcoal therapy.

DATA SOURCES:

A manual search of Index Medicus from 1970 to December 1993 was conducted for English language articles; bibliographies of the resultant articles were also scanned.

STUDY SELECTION:

Cases were included if they were described in full detail, resulted in significant morbidity or mortality, and uniquely contributed to the formulation of recommendations for safe use of activated charcoal therapy.

DATA SYNTHESIS:

The major causes of morbidity and mortality secondary to activated charcoal therapy are aspiration of charcoal, gastrointestinal obstruction, and fluid and electrolyte abnormalities. Aspirations have occurred as a result of a number of circumstances that may be avoided. These include use in patients with unprotected airways, use of excessive charcoal dose, administration of inappropriately diluted charcoal, and administration of charcoal in the field. Gastrointestinal obstruction has occurred when multiple doses of activated charcoal have been administered without a cathartic and in cases in which a cathartic was administered if the patient had impaired peristalsis. Fluid and electrolyte abnormalities have occurred secondary to excessive cathartic administration.

CONCLUSIONS:

Activated charcoal therapy should be used judiciously so that related morbidity and mortality can be prevented. Adequate consideration for the patient's airway protection capability is necessary. Judicious dosing of charcoal and concomitant cathartic therapy, along with adequate monitoring of fluid and electrolyte status, abdominal physical assessment, and clinical condition are all vital to the safe use of activated charcoal therapy.
Intravitreal Ganciclovir for Cytomegalovirus Retinitis in Patients with AIDS
Authors: Montero Ma Carmen , Pastor Maite , Buenestado Catalina , Lluch Amparo , Atienza Manuela
Published: January 2017

OBJECTIVE:

To assess the evolution of cytomegalovirus (CMV) retinitis and evaluate the possible complications associated with the use of intravitreal injections to treat this disease.

DESIGN:

A nonrandomized, retrospective study with case series was performed. The study took place over 34 months.

SETTING:

The study included patients with AIDS who developed CMV retinitis, and who were treated in the hospital, as outpatients, or both.

PATIENTS:

Twelve patients with AIDS and CMV retinitis diagnosed between June 1990 through April 1993 were included in the study.

MAIN PATIENT PARAMETERS AND OUTCOME MEASURES:

For each patient, the following data were recorded: age, risk factors, other systemic findings, dates of AIDS and CMV retinitis diagnoses, stage of AIDS, extent of the retinitis, CD4 lymphocyte count at the time of diagnosis of the retinitis, visual acuity, clinical evolution of the ocular infection, therapy, complications caused by the treatment, development of nonocular CMV, and the use of zidovudine or didanosine during the study period.

RESULTS:

Vision improved or remained stable in nine patients and worsened in three. Two patients developed optic neuritis. The retinitis progressed to the other eye in only one of the eight patients who had unilateral involvement. The rate of relapse with maintenance therapy was 8.3% (n = 1) within the first 8 weeks. Treatment was well tolerated. There was no evidence of toxicity after a total of 226 intravitreal ganciclovir injections. All patients were able to tolerate zidovudine or didanosine concomitantly with intravitreal ganciclovir.

CONCLUSIONS:

Intravitreal ganciclovir appears to be an effective alternative to systemic ganciclovir in patients with severe neutropenia and in patients who choose to continue receiving systemic zidovudine or didanosine. Early treatment and long-term maintenance therapy is essential for preserving sight.
Pain Assessment of Subcutaneous Injections
Authors: Jørgensen Jan T , Rømsing Janne , Rasmussen Mette , Møller-Sonnergaard Jørn , Vang Lisbeth , Musæus Lise
Published: January 2017

OBJECTIVE:

To compare injection pain after subcutaneous administration of four different solution volumes.

DESIGN:

Double-blind, randomized, prospective, multiple crossover study.

SETTING:

Steno Diabetes Centre, Gentofte, Denmark.

PARTICIPANTS:

Eighteen healthy volunteers, 9 women and 9 men, aged 21-30 years.

METHODS:

The subjects were injected with four different volumes (0.2, 0.5, 1.0, 1.5 mL) of NaCl 0.9%. The study was performed on 2 days with a 1-week washout period between the study days. On each study day the subjects received four injections in each thigh. To evaluate the validity of our pain assessing model the subjects received eight injections of 0.5 mL on one of the study days. Pain assessment was done immediately after each injection using both a 10-cm visual analog scale (VAS) and a six-item verbal rating scale (VRS).

RESULTS:

A significant difference in pain score on both the VAS (p < 0.05) and the VRS (p < 0.01) was seen between the four injection volumes. The pain was significantly increased with volumes of 1.0 and 1.5 mL. No significant difference in injection pain could be detected between 0.2 and 0.5 mL and between 1.0 and 1.5 mL. No significant period or carryover effect could be detected in the study. A significant correlation between the pain score on the VAS and the pain score on the VRS was found (r = 0.79, p < 0.0001).

CONCLUSIONS:

The pain of a subcutaneous injection is related to injection volume in the thigh. The results show that increasing the volume from 0.5 to 1.0 mL increases the pain significantly. The findings from this study should be considered when injection preparations for subcutaneous administration are formulated. The volume should generally be less than 1.0 mL if injected into the thigh.
Use of Salivary Caffeine Tests to Assess the Inducer Effect of a Drug on Hepatic Metabolism
Authors: Soto Javier , Sacristan Jose A , Alsar Maria J
Published: January 2017

OBJECTIVE:

To validate the use of successive salivary caffeine tests in evaluating how long inducer drugs affect hepatic metabolism. The time course of the inducer effect of rifampin found in other studies using different methodologies was chosen as the time course of reference.

DESIGN:

Open-label, prospective, longitudinal study.

SETTING:

A university hospital.

PARTICIPANTS:

Five healthy volunteers.

MAIN OUTCOME MEASURES:

Rifampin 600 mg/d was administered for 21 days. Anhydrous caffeine 300 mg was concurrently administered on each study day. Salivary caffeine tests were carried out on the following days: predose (baseline), and days 1, 5, 9, 13, and 17. Salivary tests were performed for up to 13 days after the last dose of rifampin (study days 21, 25, 29, and 33).

RESULTS:

The mean systemic caffeine clearance was increased for up to 17 days after the intake of rifampin, reaching the maximum inducer effect between days 5 and 9, and returning to previous values progressively during several days after rifampin was discontinued.

CONCLUSIONS:

Our results suggest that successive salivary caffeine measurements could be a safe, reliable, noninvasive, and suitable test for exploring the time course of the inducer effect of drugs on hepatic metabolism activity.
Impact of Pharmacist-Operated General Medicine Chronic Care Refill Clinics on Practitioner Time and Quality of Care
Authors: Cassidy Irving B , Keith Matthew R , Coffey Edward L , Noyes Margaret A
Published: January 2017

OBJECTIVE:

To assess the impact of pharmacist-operated refill clinics on practitioner (physician/physician assistant) time. Secondary objectives included assessment of disease state control, drug acquisition costs, and human resource allocation.

DESIGN:

The study ran from October 1, 1993 through January 31, 1994. At one clinic the pharmacist performed chart review only and did not see the patient. At the second site the pharmacist also interviewed the patient. The pharmacist used no treatment algorithms. Practitioner and pharmacist time before and after implementation of the refill clinics was measured on 3 consecutive days of normal clinic operation.

SETTING:

TWO state correctional facilities.

PATIENTS:

The study population consisted of patients receiving chronic care who were observed during regular clinic hours.

MAIN OUTCOME MEASURES:

We evaluated pharmacist and practitioner time before and after pharmacist involvement. Hypertension was the only disease state yielding sufficient numbers for statistical analysis. We used a two-tailed paired t-test with the a priori level set at 0.05. We also evaluated the number of patients with disease state control before and after clinic implementation, drug acquisition costs, and human resource allocation.

RESULTS:

The refill clinic pharmacist reduced practitioner time commitment in both clinics. The greatest impact on practitioner time was found in the interview clinic. Quality of care was maintained equally between the two clinics, with a positive impact on human resource allocation.

CONCLUSIONS:

In the managed care environment, pharmacist-run refill clinics can decrease practitioner time commitment allowing reallocation of human resources while maintaining current quality of care.
Modified Oral Ondansetron Regimen for Cyclophosphamide-Induced Emesis in Lupus Nephritis
Authors: Yarboro Cheryl H , Wesley Robert , Amantea Michael A , Klippel John H , Pucino Frank
Published: January 2017

OBJECTIVE:

To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed.

DESIGN:

A before-after prospective observational pilot project.

SETTING:

A federal research hospital.

PATIENTS:

Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75–1.0 g/m2 had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4–16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion.

MAIN OUTCOME MEASURES:

The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated.

INTERVENTIONS:

To account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule, in which ondansetron is administered prior to chemotherapy.

RESULTS:

NO emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the true rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/ dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/ dexamethasone tablets and oral administration of ondansetron using the intravenous formulation.

CONCLUSIONS:

This study suggests that a modified oral ondansetron/ dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis.
Stability and Compatibility of Fluorouracil with Morphine Sulfate and Hydromorphone Hydrochloride
Authors: Xu Quanyun A , Trissel Lawrence A , Martinez Juan F
Published: January 2017

OBJECTIVE:

To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with morphine sulfate 1 mg/mL and with hydromorphone hydrochloride 0.5 mg/mL in dextrose 5% injection and in NaCl 0.9% injection.

DESIGN:

Test solutions of the drugs in dextrose 5% and in NaCl 0.9% were prepared in triplicate and stored at −20, 4, 23, and 32°C. Samples were removed immediately and at various time points over 35 days and stored at −70 °C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter and particle content with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC.

RESULTS:

The morphine test solutions all rapidly developed crystalline precipitation when admixed with fluorouracil. Further, substantial loss of morphine content, usually around 60-80%, occurred in all samples within 24 hours at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the fluorouracil with hydromorphone test solutions at any of the time points. Further, there was no loss of fluorouracil over 7 days at 32 °C and 35 days at 23, 4, and −20 °C. Hydromorphone also was stable for 7 days at 32 °C and for 35 days at the other temperatures when combined with fluorouracil 1 mg/mL and at −20 and 4 °C with fluorouracil 16 mg/mL. However, with fluorouracil 16 mg/mL, hydromorphone was stable only for 3 days at 32 °C and for 7 days at 23 °C, exhibiting approximately 10% loss after those times.

CONCLUSIONS:

When admixed in dextrose 5% injection and NaCl 0.9% injection, fluorouracil 1 and 16 mg/mL and morphine 0.5 mg/mL were immediately physically incompatible in all samples resulting in substantial loss of morphine content as precipitated crystals. Fluorouracil 1 mg/mL plus hydromorphone 0.5 mg/mL were compatible and stable for at least 7 days at 32 °C and for at least 35 days at 23, 4, and −20 °C. Admixed with fluorouracil 16 mg/mL, hydromorphone was stable for 3 days at 32 °C, 7 days at 23 °C, and 35 days at 4 and −20 °C.
Phenytoin in Wound Healing
Authors: Anstead Gregory M , Hart Lisa M , Sunahara Janice Fong , Liter Melvin E
Published: January 2017

OBJECTIVE:

To describe a patient with a massive Grade IV pressure ulcer that responded rapidly to treatment with topical phenytoin and to review the literature supporting the use of this therapy.

CASE SUMMARY:

A 55-year-old morbidly obese white man (266 kg), with respiratory failure secondary to obesity-hypoventilation syndrome and heart failure, developed pressure ulcers on his lower back and sacrum within the first 2 weeks of hospitalization. Traditional methods of treatment were unsuccessful, and by day 79, the wound involved the entire lumbosacral area and buttocks, and had extensive undermining and sinus tract formation. Within 2 days of applying topical phenytoin, fresh granulation tissue was apparent. After 54 days of treatment, nearly all the sinus tracts were healed. Four months after treatment with topical phenytoin was begun, the sacral wound was nearly healed and the lumbar wound was much reduced in size. It was evident that phenytoin had facilitated the healing of the wounds, even though the patient's multiple underlying medical problems had not resolved.

DISCUSSION:

Phenytoin has been used in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, and bums. Many of the existing clinical studies have methodologic flaws, such as inappropriate statistical analysis, inadequate control groups, and the absence of randomization and double-blinding. Nevertheless, all the studies have reported enhancement of wound healing, with insignificant adverse effects. Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity.

CONCLUSIONS:

Phenytoin promoted the healing of a massive, necrotizing soft tissue wound that was unresponsive to conventional treatment. Clinical success in this difficult case and the other reports in the literature suggest that phenytoin is effective in wound healing and deserves further investigation.
Cisplatln Nephrotoxicity in a Patient with a Single Kidney
Authors: Udeani George O , Singh Karanjit , Mullane Michael R , Lad Thomas E
Published: January 2017

OBJECTIVE:

To describe a patient with a single kidney who experienced cisplatin-associated nephrotoxicity.

CASE SUMMARY:

A 78-year-old African-American woman with squamous cell carcinoma of the base of her tongue (T4N2M1) was admitted electively to our institution for the first cycle of chemotherapy. Her past medical history was significant for a left nephrectomy secondary to well-differentiated papillary transitional cell carcinoma of the left renal pelvis, hypothyroidism, asthma, and coronary artery disease. Her blood urea nitrogen (BUN) was 27 mg/dL of urea, and serum creatinine was 1.2 mg/dL. On admission she was hydrated adequately, and was treated with an evening dose of cisplatin 100 mg/m2 (180 mg) in 250 mL of NaCl 0.9% solution in a 3-hour infusion, and a 5-day course of fluorouracil 1000 mg/m2 (1800 mg) in a 24-hour infusion. Serum creatinine and BUN concentrations following cisplatin administration were 1.1 mg/dL and 8 mg/dL, respectively. Four days after cisplatin therapy, a decline in renal function was observed, with an increase in serum creatinine and BUN concentrations to 4.0 mg/dL and 31 mg/dL, respectively. These tests remained elevated throughout her hospitalization. With hemodialysis treatments a resolution in altered mental status was observed; however, her chronic renal failure persisted. She was subsequently discharged and followed in the outpatient renal, geriatric, and oncology clinics.

DISCUSSION:

Cisplatin is a principal chemotherapeutic agent used in the treatment of a variety of solid tumors. Nephrotoxicity is a major complication associated with this compound. Although many clinicians believe that cisplatin nephrotoxicity is unlikely to occur in patients with a single kidney, recent reports have suggested otherwise. The physiologic changes of the aging kidney are such that they should foster cisplatin clearance rather than expose the kidney to the drug's nephrotoxic potential. In addition, evening administration of cisplatin is thought to minimize nephrotoxicity. We describe a 78-year-old woman with a single kidney who developed nephrotoxicity following a single evening dose of cisplatin. Details of the patient's history and cisplatin-associated complication and therapy are discussed.

CONCLUSIONS:

Cisplatin circadian rhythmic pharmacotherapy to minimize cisplatin toxicity in patients with a single kidney appears to be controversial and needs further evaluation.
Current Issues in Treating the Hypertensive Patient with Diabetes: Focus on Diabetic Nephropathy
Authors: Cziraky Mark J , Mehra Ila V , Wilson Marcus D , Bakris George L
Published: January 2017

OBJECTIVE:

To review the pathophysiology of hypertension and complications in patients with diabetes mellitus, specifically focusing on diabetic nephropathy; to evaluate the current clinical literature regarding the appropriate management of hypertension in this patient group; and to offer treatment recommendati

DATA SOURCES:

A MEDLINE search of applicable English-language clinical studies, abstracts, and review articles pertaining to hypertension, diabetes, and diabetic nephropathy.

STUDY SELECTION:

Relevant studies on humans, examining hypertension, diabetes, and diabetic nephropathy, and the effects of drug therapy on these interrelated disease states.

DATA SYNTHESIS:

Pathophysiology of hypertension in the patient with diabetes mellitus and the pathophysiology of diabetic nephropathy are discussed. Studies evaluating the therapeutic effect of certain antihypertensive agents, their effect on glucose control and insulin sensitivity, and the progression of diabetic nephropathy are reviewed. Recommendations on the treatment of the patient with diabetes and hypertension are given.

CONCLUSIONS:

The treatment of the patient with diabetes mellitus and hypertension remains complex. Interventions in this patient population should not only decrease blood pressure, but also reduce the risk of both vascular and nonvascular complications. Data support the theory that by controlling a patient's hypertension, the incidence of albuminuria and the progression of diabetic nephropathy are slowed. Additionally, data are available to support the use of pharmacologic interventions in nonhypertensive patients with diabetes and proteinuria. Drug therapies that have produced reductions in proteinuria in this patient population include angiotension-converting enzyme inhibitors and nondihydropyridine calcium-channel antagonists. Additional information is needed to better differentiate the individual agents within each of the antihypertensive drug classes regarding their individual effects on the patient with diabetes and hypertension, specifically effects on diabetic nephropathy and its progression to endstage renal disease.
Dual Calcium-Channel Blocker Therapy in the Treatment of Hypertension
Authors: Saseen Joseph J , Carter Barry L
Published: January 2017

OBJECTIVE:

To review the in vitro receptor binding data of calcium-channel blockers (CCBs) and in vivo studies in humans regarding the use of dual calcium-channel blocker therapy, with a focus on the use of this therapy for hypertens

DATA SOURCE:

A MEDLINE search was conducted to identify literature pertaining to CCBs.

STUDY SELECTION:

In vitro studies and investigations that evaluated CCB receptor binding and the interactions between subclasses of CCBs were chosen. All studies in humans and clinical trials that evaluated the use of dual CCB therapy in the treatment of cardiovascular diseases were selected for review. Also, case reports describing the use of dual CCB therapy were included in this article.

DATA EXTRACTION:

The methodology, results, and conclusions of the selected data were evaluated. Data regarding the in vitro receptor binding kinetics of CCBs, as well as interactions, were reported. Because there is limited information on dual CCB therapy for hypertension, clinical studies using this treatment for ischemic heart disease were also reviewed. They were summarized and compared on the basis of the degree of disease control (e.g., blood pressure, exercise tolerance), adverse effects, and other clinical endpoints of pharmacologic therapy.

DATA SYNTHESIS:

In vitro studies have identified binding sites for the dihydropyridine (nifedipine), diphenylalkylamine (verapamil), and benzothiazepine (diltiazem) subclasses of CCBs, and indicate that they are allosterically related to each other within the voltage-sensitive calcium-channel receptor. Dihydropyridine binding affinity is decreased with concomitant verapamil binding, but is enhanced by concomitant diltiazem binding. Dual CCB therapy has been shown to be efficacious in patients with ischemic heart disease. Although this therapy is limited by dose-related adverse effects, it appears to have an important role in patients with ischemia that is refractory to conventional therapy, or for those whose therapeutic options are limited by contraindications. Theoretically, many patients with hypertension may benefit similarly from dual CCB therapy. Because data evaluating this treatment option are sparse, recommendations regarding safety, efficacy, and the role of dual CCB therapy for hypertension would be premature.

CONCLUSIONS:

Controlled data evaluating dual CCB therapy for the treatment of hypertension are lacking. This treatment modality may be beneficial in the future, but requires further investigation to determine safety and efficacy.
Is There a Therapeutic or Pharmacokinetic Rationale for Amphotericin B Dosing in Systemic Candida Infections?
Authors: Nagata Maureen P , Gentry Chris A , Hampton Edward M
Published: January 2017

OBJECTIVE:

To review the literature regarding the dosage of amphotericin B in Candida infections. The correlation or rationale of current dosing practices is assessed in light of the literature.

DATA SOURCES:

A MEDLINE search encompassing the years 1968-1995 was used to identify pertinent literature. Additional references were obtained from the articles retrieved from MEDLINE.

STUDY SELECTION:

Studies that directly assessed amphotericin B dosage and/or duration, pharmacokinetic literature dealing with plasma concentrations and amphotericin B disposition, and literature dealing with dose and/or concentration as well as clinical outcome were selected for inclusion. Additional relevant citations were used in the introductory material and discussion.

DATA EXTRACTION:

Although there was a large number of articles related to amphotericin B, surprisingly few large studies were designed to address the issues in question. The description of the methods and results of these heterogeneous articles are the basis of this review. Although additional controlled studies with more subjects need to be performed, the results to date provide a foundation from which to make some inferences regarding optimal use of this therapeutic modality until more definitive data become available.

DATA SYNTHESIS:

Despite numerous articles addressing the pharmacokinetics of amphotericin B, little is known about its tissue distribution, the rate of transfer of the drug from vascular to peripheral sites, or its terminal disposition. Less information is available regarding the relevance of pharmacokinetic parameters or serum concentrations to clinical outcome. Most of the articles mentioning dosing provide little or no justification for the dosages employed. The variety of the dosages used and the heterogeneity of the populations studied make determinations of dose-outcome relationships difficult.

CONCLUSIONS:

From the available clinical data, it appears that early initiation of amphotericin B therapy is crucial to a favorable outcome. Daily dosing initially followed by every-other-day administration of twice the daily dose is better tolerated by the patient than daily dosing and produces a similar therapeutic outcome. The drug should be continued until therapeutic endpoints have been achieved, rather than until a specific total dosage has been administered. The nephrotoxicity that occurs with amphotericin B administration is apparently reversible and should not be used as an endpoint for therapy if total dosages do not exceed 4 g. Additional well-designed, controlled trials evaluating standardized dosing methods of amphotericin B with predetermined dosing regimens and/or definitive therapeutic endpoints are needed to determine the optimal dosing approach for this agent.
Nontuberculous Mycobacterial Infections
Authors: Guay David RP
Published: January 2017

OBJECTIVE:

To review the epidemiology, clinical manifestations, diagnosis, and treatment of nontuberculous mycobacterial infections other than Mycobacterium avium complex (MAC).

DATA SOURCES:

A MEDLINE search of English-language literature pertaining to nontuberculous mycobacteria other than MAC was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search.

STUDY SELECTION AND DATA EXTRACTION:

All articles were considered for possible inclusion in the review. Information judged by the author to be pertinent was selected for discussion.

DATA SYNTHESIS:

Mycobacterial infections, including those caused by nontuberculous mycobacteria other than MAC, have assumed greater importance over the past decade, due in part to the changing spectrum of immunosuppression as manifested by organ transplantation and HIV infection. Many pathogenic nontuberculous mycobacteria have been identified that are associated with a wide variety of localized, organ-specific, and systemic infections. Of concern, these organisms exhibit variable, species-specific susceptibility to traditional antimycobacterial drugs and other antimicrobials. In addition, long treatment courses and adjunctive surgical therapy are often required to effect cure. Important antimicrobials for the management of these infections include cefoxitin, imipenem/cilastatin, aminoglycosides (other than streptomycin), tetracyclines, macrolides, and trimethoprim/ sulfamethoxazole, as well as traditional antimycobacterials.

CONCLUSIONS:

Nontuberculous mycobacteria have assumed an increasing role in disease etiology in both nonimmunocompromised and immunocompromised individuals. Advent of rapid diagnostic techniques and susceptibility testing has allowed the clinician to identify these organisms and initiate effective treatment on a more timely basis with an improved chance for cure. Few therapeutic agents are available for treatment of these infections, many of which are not considered classic antimycobacterials.