bluuebunny/crossref_metadata_2025 huggingface dataset:
Clindamycin Associated Diarrhea
Authors: Stewart Ronald B. , Lee J. Douglas , Scrivens John J.
Published: June 2017

To determine the incidence of diarrhea and colitis associated with antibiotic therapy, a retrospective study utilizing chart reviews, autopsy reports and questionnaires was undertaken. Matched groups of patients who had received clindamycin, tetracycline, or chloramphenicol were studied. The incidence of diarrhea was similar for each group. No instances of colitis were identified. Clindamycin produced no more diarrhea than other antibiotics.
Acute Otitis Media
Authors: Bosso John A. , Jackman Jerald R.
Published: June 2017

A typical case of acute otitis media in a pediatric patient is presented. The pathophysiology of the disorder, as well as its incidence, etiology, complications, and sequelae are discussed. Past treatment methods and current therapeutic recommendations pertaining to antibiotics and other adjuncts are included.
Activity Analysis and Cost Study of Clinical Pharmacists Practicing in a University Medical Center
Authors: Barsness Frederick R. , Trinca Carl E.
Published: June 2017

The activities of three staff clinical pharmacists practicing in a university medical center hospital were studied using work sampling direct observation techniques. The results of the activity analysis were compared with the functional criteria of the Task Force on the Pharmacist's Clinical Role. It was found that the clinical pharmacists devoted a large portion (72.36 percent) of their total practice time to accomplishing professional activities. A very low percentage (2.27) of time was observed to be spent in nonproductive idle time. The cost to provide clinical pharmacy services to the 165.23 average census of inpatients supported by the clinical pharmacists was calculated to be $1.18 per patient per day. It was concluded that the observed pharmacists were highly motivated and provided a wide variety and extensive amount of professiosal clinical pharmacy services. Recommendations were made calling for research of other clinical pharmacy practice models, standardization of pharmacy activity terminology, determination of clinical pharmacy outcomes and identification of motivational factors present in the study model environment.
Possible Interaction of Indomethacin and Warfarin
Authors: Self Timothy H. , Soloway Mark S. , Vaughn Don
Published: June 2017

A case report of a possible interaction between indomethacin and warfarin is presented. The effect of warfarin on the prothrombin time (PT) was enhanced while indomethacin was given concurrently. Substitution of Ibuprofen for indomethacin resulted in the desired control of the prothrombin time.

Based on the results of controlled clinical trials and on the rarity of case reports, there is probably an extremely low incidence of enhancement of warfarin-induced hypoprothrombinemia by indomethacin.
Drug-Induced Heat Stroke
Authors: Mirtallo Jay M.
Published: June 2017

It is seldom recognized that heat stroke can be precipitated by drug therapy. Drugs that alter normal body thermoregulation and the mechanisms of drug action on thermoregulation are discussed, together with normal body thermoregulation and heat stroke. Complications arising from heat stroke and their treatment are presented.
Effect of Assay Methodology on the Prediction of Lithiumc Maintenance Dosage
Authors: Karki Shyam D. , Carson Stanley W. , Holden J.M.C.
Published: June 2017

Test dose methods have been used to predict the maintenance dosage of lithium carbonate tablets in bipolar patients. These methods require a lithium analytical method that is accurate to the second decimal place. Successful use of these test methods has employed the atomic absorption spectrophotometric method, yet many hospitals use a flame spectrophotometric method. We evaluated a two-point method to predict lithium maintenance dosages of slow-release lithium carbonate tablets in 20 bipolar patients using both assay methodologies. No clinically significant differences were found between the two sets of predictions, suggesting that either assay methodology has requisite sensitivity and accuracy for use in test dose predictions of lithium maintenance dosages.
Branched-Chain Amino Acid Support of Stressed Patients
Authors: Oki Julie C. , Cuddy Paul G.
Published: June 2017

Branched-chain amino acid-enriched formulas have been evaluated in a number of clinical trials. The efficacy of these solutions in the management of stressed patients is controversial. This review discusses the proposed benefits of the branched-chain amino acid-fortified solutions and summarizes prospective clinical trials regarding their use in stressed patients. A cost comparison is also included.
Do Parenteral Nutrition Solutions with High Concentrations of Branched-Chain Amino Acids Offer Significant Benefits to Stressed Patients?
Authors: Teasley Kathleen M. , Buss Renee L.
Published: June 2017

The critically ill, stressed patient has been characterized as having altered cellular metabolism. Altered protein metabolism is manifested as negative nitrogen balance, reduced whole-body protein synthesis, and increased proteolysis. An increased oxidation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine has also been observed. Exogenous administration of BCAA as part of a total parenteral nutrition (TPN) regimen has been proposed to compensate for the altered protein metabolism in the stressed patient by sparing endogenous sources of BCAA, thereby reducing skeletal muscle catabolism and increasing protein synthesis. Numerous clinical studies have been performed investigating this theory. The results are controversial. Differences in study outcomes appear to be related to study design, especially patient selection. Our review of those studies which were randomized, prospective, and controlled indicates that an improvement in nitrogen retention and visceral protein status can be achieved in stress-stratified patients who receive a TPN regimen containing a BCAA-enriched formula. The significance of these outcomes on morbidity, length of hospital stay, and mortality has not been evaluated.
Potassium Iodide as a Thyroid Blocker—Three Mile Island to Today
Authors: Halperin Jerome A.
Published: June 2017

The Three Mile Island (TMI) nuclear emergency in the U.S. in March 1979 marked the first occasion when use of potassium iodide (KI) was considered for thyroid blocking of the population in the vicinity of a potentially serious release of fission products from a nuclear power reactor. In face of a demand that could not be satisfied by commercial supplies of low-dose KI drug products from the U.S. pharmaceutical industry, the Food and Drug Administration directed the manufacture and stockpiling of sufficient quantities of saturated solution of potassium iodide (SSKI) to provide protection for one million people in the event of a large-scale release of radioiodines. Although the drug was not used, the experience of producing, stockpiling, and making ready for use a large quantity of the drug resulted in significant public policy, regulatory, and logistical issues. A number of these issues have been resolved through scientific debate and consensus, development of official guidance regarding the proper role of KI in nuclear emergencies, and the approval of New Drug Applications for KI products specifically intended for thyroid blocking in nuclear emergencies. Other issues regarding broad-scale implementation of the guidelines remain today. This paper traces the history of the development and implementation of the use of KI from pre-TMI to the present.
Tobramycin Administrationc and Blood Sampling through a Dual-Lumen Peripheral Intravenous Catheter
Authors: Pleasants Roy A. , Williams Dennis M. , Fus Andrea S. , Leathers Cathy M. , Waltner William E.
Published: June 2017

The objective of this study was to determine if a peripheral dual-lumen catheter could be used for accurate tobramycin blood concentration measurement when drug administration and blood sampling were undertaken through separate lumens of the catheter. Eleven adult volunteers received tobramycin 1.5 mg/kg iv infused over 30 minutes through the distal lumen of the dual-lumen catheter every eight hours for two doses. Multiple blood samples were obtained concurrently from the proximal lumen of the catheter and a single-lumen catheter in the contralateral arm after each dose. Blood samples were also obtained through the distal lumen before and 30 minutes after the end of the infusion. Accurate blood samples were obtainable through the dual-lumen catheter in only 5 of 11 subjects due to either infiltration or difficulties in catheter placement. In the subjects from whom accurate blood samples were obtained, approximately 20 minutes postinfusion was the amount of time required before measured tobramycin serum concentrations were similar between the arm in which the drug was infused (site of the dual-lumen catheter) and the contralateral arm. At standard times for obtainment of trough (just prior to the infusion) and peak (30 minutes after the end of a 30-minute infusion) tobramycin serum concentrations from the proximal lumen of the dual-lumen catheter were numerically similar to those obtained from the contralateral arm. This preliminary study indicates that the dual-lumen catheter provides accurate aminoglycoside concentrations when patent relative to blood withdrawal and if peak blood samples are obtained at least 30 minutes postinfusion through the recommended lumen. However, further study in a larger number of subjects is required before routine use of this device can be recommended.
Time to Steady State following a Change in Dosing Rate
Authors: D'Angio Richard G. , Gwilt Peter R.
Published: June 2017

Drugs administered at fixed intervals or by continuous infusion will accumulate in the body until steady state is achieved. The time to a given percentage of the eventual steady-state concentration has previously been considered to be dependent only on the elimination half-life. This is incorrect. Although the rate of drug accumulation in the body is dependent only on the elimination half-life, the time to a given percentage of steady state is dependent on both the elimination half-life of the drug and the initial concentration. This paper presents the mathematical proof of this concept, computer simulations demonstrating the use of these equations, and nomograms for use in clinical practice. The use of this method allows serum drug concentrations to be evaluated earlier than previously predicted after changes in the dosing rate.
Alternative Dosing Strategy for Aminoglycosides: Impact on Efficacy, Nephrotoxicity, and Ototoxicity
Authors: Chan Gary L.C.
Published: June 2017

Accumulating evidence suggests that the therapeutic margin of aminoglycoside therapy may be improved by manipulation of dosing strategy. Recent understanding of concentration-dependent bactericidal activity and postantibiotic effect argues that the aminoglycosides may be administered in larger doses and at longer dosing intervals than currently recommended without compromising efficacy. Preliminary clinical experience suggests that once-daily regimens are as efficacious as conventional intermittent injections in the treatment of gram-negative infections including urinary tract infections, cystic fibrosis, and bacteremia in nonneutropenic patients. The transient, high peak serum concentrations achieved in once-daily dosing have not been associated with excessive nephrotoxicity or ototoxicity thus far. Decreased accumulation in renal cortex as a result of saturable renal uptake after the single daily dose may even reduce the incidence or severity of renal damage. Further studies on more patients are required to substantiate these preliminary findings.
Nifedipine in the Treatment of Hypertensive Episodes in the Coronary Care Unit
Authors: Malesker Mark A. , Rovang Karen S. , Mohiuddin Syed M. , Mooss Aryan N. , Hilleman Daniel E. , Sketch Michael H.
Published: June 2017

The effectiveness of nifedipine for the treatment of acute hypertensive episodes in patients already taking chronic calcium-channel blocker therapy is unknown. We report our experience with 43 consecutive patients who received nifedipine for acute hypertensive episodes in the coronary care unit. Of the 43 patients (24 men, 19 women), 23 (53 percent) were taking chronic (>2 mo) calcium-channel blocker therapy. Nifedipine 10 mg capsules were chewed and swallowed with repeat doses given at hourly intervals if necessary. Target BP was 140/90 mm Hg, which was achieved in 31 of 43 patients (72 percent). In patients already taking calcium-channel blockers, target BP was achieved in 18 of 23 patients (78 percent). Response in patients not taking chronic calcium-channel blockers was observed in 13 of 20 patients (65 percent). Overall, adverse effects occurred in 16 of 43 patients (37 percent): 11 of 23 patients (48 percent) taking calcium-channel blockers, and 5 of 20 patients (25 percent) not taking calcium-channel blockers. Nifedipine is equally effective in lowering BP in patients taking calcium-channel blockers as it is in patients not taking them. Although associated with a higher incidence of adverse effects in patients already taking calcium-channel blockers, these effects were not considered serious. Nifedipine is an effective agent in acute hypertensive episodes, even in patients receiving chronic calcium-channel blocker therapy.
Acute Hypotensive Reaction to Etoposide with Successful Rechallenge: Case Report and Review of the Literature
Authors: Cersosimo Robert J. , Calarese Pamela , Karp Daniel D.
Published: June 2017

Hypotension, bronchospasm, and facial flushing associated with an intravenous infusion of etoposide occurred in a 38-year-old man with advanced testicular cancer. The reaction began within three minutes after the initiation of the infusion and was reversed with intravenous fluids and diphenhydramine. He was successfully retreated with four additional doses of etoposide after pretreatment with diphenhydramine and dexamethasone. The literature concerning similar anaphylactoid reactions to intravenous etoposide is reviewed.
Clinical Pharmacy Education in New England: A Report of the Whispering Pines Conference
Authors: Fish Susan S. , Mattea Edward J. , Thrasher Kimberly A. , Cardoni Alex A. , Cohen Louise Glassner , Gundlach Catherine , Labreche Dustan G. , Mutnick Alan H.
Published: June 2017

Clinical pharmacy practice as it relates to the future of the pharmacy profession has been examined at Hilton Head in 1985 and at regional conferences throughout the U.S. between 1986 and 1988. However, clinical pharmacy education and its role in the future of the profession had not been the focus of this type of “futuristic” conference. In 1988, the clinical pharmacy faculties from the four colleges of pharmacy in New England met to discuss the “Directions for Clinical Pharmacy Education in New England.” Through a series of workshops, and stimulated by challenges from keynote speakers, the participants focused on the current status of clinical pharmacy education in New England, the barriers to change, and the strategies required to accomplish these changes. Consensus on prioritization of changes and their strategies was reached, and those that could be implemented in the near future were identified. Since the conference, changes have occurred and the professional networking that began at the conference has continued. This paper is a summary of the proceedings of this conference.
An Assessment of the Drug Therapy Education Preferences of an Interdisciplinary Group Interested in the Elderly
Authors: Elliott David P. , Harvit Pamela A.
Published: June 2017

A survey was conducted to measure the drug therapy education preferences of a diverse group of professionals interested in the elderly. Two hundred forty-four surveys were mailed and 119 were returned (48.8 percent). Seventy-two percent of the respondents were social workers; four percent were registered nurses; the remainder of the respondents (24 percent) were non-health professionals. Most respondents liked all common methods of instruction except self-directed activities and large group discussions. The five topics of greatest interest were drug interactions, adverse drug effects, drugs used to treat depression, drugs used to treat nervousness or anxiety, and drugs used to manage dementia. A survey is an economical means of assessing the preferences of an unfamiliar audience. The methods used to determine content for this program can be used by educators who are planning programs for similar audiences made up of health and non-health professionals.
Altered Theophylline Metabolism in Patients with Psoriasis
Authors: West Dennis P. , Fischer James H. , Barbour Marilyn McFarland , Cwik Michael J. , Micali Giuseppe , Fiedler Virginia C.
Published: June 2017

We observed two patients on theophylline therapy with concomitant severe psoriasis and a two- to threefold greater theophylline clearance than that reported in healthy, nonsmoking adults. There were no factors known to induce theophylline clearance. In both cases, the induction of theophylline metabolism was relatively selective for the 1-methyluric acid pathway. The altered metabolism in these patients appeared to correlate with the clinical severity of the disease. The data suggest the possibility that an observed lack of efficacy for theophylline in psoriasis may be related to pharmacokinetic effects. The concept that altered drug metabolism may occur in the presence of skin disease has important implications for pharmacotherapeutics in dermatology.
Drug Prescribing in Residential Homes for Elderly People in the United Kingdom
Authors: Stewart Ronald B. , Weedle Peter B. , Poston Jeffrey W. , Parish Peter A.
Published: June 2017

Data relating to the use of medicines from a descriptive epidemiologic study of drug use in 55 residential homes for elderly people in Britain were analyzed. Of the 1888 residents included in the study, 1617 (85.6 percent) received a total of 5535 medicines. The median number of medicines received per day was three and the per-day range varied from one to thirteen medicines. Significantly more women than men received medicines and women also received more medicines each. The most frequently prescribed groups of medicines were those acting on the central nervous (34.0 percent), the cardiovascular (27.2 percent), and on the gastrointestinal (8.9 percent) systems. Deficiencies were identified in doses, duration, and selection of drugs in certain therapeutic groups.
A Model of Methods for Influencing Prescribing: Part II. A Review of Educational Methods, Theories of Human Inference, and Delineation of the Model
Authors: Raisch Dennis W.
Published: June 2017

The purpose of this literature review is to develop a model of methods used to influence prescribing. This article reviews well-controlled studies of educational efforts, describes and relates theories of human inference to these studies, and delineates a model of methods for influencing prescribing. The model can be used to help explain the success or failure of various programs and as a framework for developing and testing methods to influence prescribing.
Influence of Dissolution Rate and pH of Oral Medications on Drug-Induced Esophageal Injury
Authors: Bailey Robert T. , Bonavina Luigi , Nwakama Patrick E. , DeMeester Tom R. , Cheng Shih-Chuan
Published: June 2017

The in vitro dissolution time and pH were measured for 16 drug products in capsule or tablet form representative of oral medications known to cause esophageal injury. The test drugs included Vibramycin, Minocin, quinidine sulfate, Cleocin HCl, Indocin, Tolectin 200, ferrous sulfate, vitamin C, aspirin, Procardia, phenobarbital, Dilantin, Butazolidin, Noctec, K-Dur, and Quinaglute. Artificial saliva (10 mL) was placed in a small beaker along with a pH probe connected to a digital display pH meter and a strip—chart recorder. The salivary pH was measured at baseline and continuously during the dissolution of each test medication and the time taken for complete dissolution was recorded. This experiment was repeated six times for each drug. Baseline and final dissolution pH were compared statistically for differences using the Wilcoxon matched-pairs signed-ranks test. Significance was established at the 0.05 level. Only three medications tested (vitamin C, aspirin, and Dilantin) produced a dissolution pH outside the range of physiological esophageal pH values. Although the majority of the test drugs significantly altered the baseline pH, the final dissolution pH did not fall outside the physiologic range. Nine of the 16 test drugs dissolved completely within 10 minutes, whereas the remaining 7 drugs took 30 minutes or longer (up to 24 hours) to dissolve. We conclude that the dissolution pH of potentially caustic medications does not appear to be a primary mechanism of drug-induced esophageal injury, whereas a rapid dissolution rate may play an important role in the pathogenesis of the lesion.
Seizure with Ciprofloxacin and Theophylline Combined Therapy
Authors: Karki Shyam D. , Bentley David W. , Raghavan Murli
Published: June 2017

Ciprofloxacin has been reported to cause theophylline toxicity by inhibiting theophylline metabolism. A 93-year-old woman without a known seizure history, while on ciprofloxacin and theophylline combined therapy, experienced a grand mal seizure. Her serum theophylline concentration at the time was 20 μg/mL. On previous occasion of theophylline toxicity, she had a serum theophylline concentration of 27 μg/mL but the patient did not experience any seizure. Several reports suggest that the combination of theophylline and ciprofloxacin has an additive inhibitory effect on gamma-aminobutyric acid (GABA) sites. Inhibition of the binding of GABA to its receptor sites has been related to the convulsant effects of other drugs. The seizure in our patient may have been caused by altered pharmacokinetics and pharmacodynamics brought about by combined therapy of theophylline and ciprofloxacin.
High-Dose Phenylephrine Infusion in the Hemodynamic Support of Septic Shock
Authors: Bonfiglio Mark F. , Dasta Joseph F. , Gregory James S. , Townsend Michael C. , Reilley Thomas E. , Flancbaum Louis
Published: June 2017

A 75-year-old man with hyperdynamic septic shock and vasodilation was successfully supported hemodynamically for 88.5 hours through the use of a continuous infusion of phenylephrine at dosages up to 360 μg/min. The only other vasoactive compound administered was dopamine at a dosage of 3.4 μg/kg/min. Hemodynamic evaluation indicated improvements in mean arterial pressure, cardiac output, and oxygen transport parameters during the period of hemodynamic support, which did not indicate a detrimental effect on perfusion of vital organs and tissues despite the use of this vasoconstrictor. Phenylephrine's pharmacologic properties may represent an advantage for its use as a vasoconstrictor over catecholamines such as norepinephrine and dopamine, particularly in patients who develop tachyarrhythmias with these agents. The pharmacology, dosage, and appropriate monitoring of therapy with phenylephrine in patients with septic shock are discussed.
Fixed Drug Eruption following Rifampin Treatment
Authors: Mimouni Aviva , Hodak Emmilia , Mimouni Marc
Published: June 2017

A case of fixed drug eruption (FDE) associated with ingestion of rifampin in a young physician is reported. The drug was prophylactically administered because of a previous close contact with a meningococcemic patient. The eruption consisted of two solitary painless purplish lesions located over the extensor surface of the left forearm, characteristic of FDE, except for the absence of residual hyperpigmentation. It is suggested that slight lesions of FDE could be unnoticed or misdiagnosed, thus raising the possibility that such skin reactions to rifampin are more frequent than is reflected in the literature.
Preventing Upper Gastrointestinal Bleeding in Patients Receiving Nonsteroidal Antiinflammatory Drugs
Authors: Elliott David P.
Published: June 2017

Severe upper gastrointestinal (GI) bleeding is a serious adverse effect of nonsteroidal antiinflammatory drugs (NSAIDs) and the elderly are at increased risk of developing this complication. Bleeding episodes can be prevented. Replacing NSAIDs with acetaminophen may be appropriate when a simple analgesic is needed that eliminates the risk of GI bleeding. Using the lowest effective NSAID dose may decrease the incidence and severity of NSAID gastropathy. Histamine H2-receptor antagonists, sucralfate, and misoprostol have been studied for the prevention of NSAID gastropathy, but only misoprostol prevents mucosal injury in both the stomach and duodenum. Patients who have a history of peptic ulcer disease or gastric bleeding from NSAIDs are candidates for prophylactic measures. Although other patients are at risk, no one knows who should receive prophylactic therapy for NSAID gastropathy. Future studies should attempt to define patient populations that warrant prophylactic therapy.
Flumazenil: A Benzodiazepine Antagonist
Authors: Karavokiros Kellie A. Tefakis , Tsipis Gaylene B.
Published: June 2017

Although benzodiazepines have been proven safe and effective for the induction and maintenance of sedation, some instances require the reversal of these events prior to the natural process of metabolism and elimination. Flumazenil, a 1,4-imidazobenzodiazepine, is an antagonist that can reduce or terminate benzodiazepine effects in a dose-dependent manner. The antagonist acts by the competitive inhibition of benzodiazepines at their central nervous system receptor sites. When administered intravenously in incremental doses, flumazenil allows for optimal patient response on an individual basis. Despite its short elimination half-life, small doses of flumazenil are usually effective in producing benzodiazepine reversal. Flumazenil's short duration of activity is due to its rapid hepatic metabolism and elimination. Intravenous antagonist doses of 0.2 mg followed by 0.1 mg/min to a total dose of 1 mg have produced significant results in reversing benzodiazepine sedation. As much as 5 mg of flumazenil have been necessary when treating benzodiazepine or mixed-agent intoxications. In such situations, response rarely exceeds a duration of one hour. If resedation occurs, additional doses or an infusion of the antagonist may provide the desired response. Flumazenil is well tolerated locally as well as systemically. Nausea and vomiting occurring after anesthesia is the most documented adverse effect in both placebo and treatment populations. However, there has been no significant difference in the occurrence of vomiting in placebo compared with flumazenil-treated subjects. Careful observation and slow reversal of central nervous system depression is crucial in the avoidance of benzodiazepine withdrawal in those patients dependent upon these agents. Flumazenil appears to provide a mechanism for the safe and effective reversal of benzodiazepine-induced sedation. At this time, the full scope of the clinical uses for this unique drug have yet to be explored.
Stability of Labetalol Hydrochloride in Distilled Water, Simple Syrup, and Three Fruit Juices
Authors: Nahata Milap C.
Published: June 2017

Labetalol hydrochloride (HCl) is an effective antihypertensive drug. It is available in a tablet dosage form, which may be difficult to administer to geriatric and pediatric patients. The tablets can be suspended in various liquid vehicles, but its stability under these conditions is unknown. The objective of our study was to determine the stability of labetalol HCl in five liquid vehicles, in both plastic and glass prescription bottles, over a four-week period at room temperature and under refrigeration. Labetalol HCl tablets (Trandate, Glaxo) were triturated, and suspended in distilled water, simple syrup, apple juice, grape juice, and orange juice to approximate concentrations of 7–10 mg/mL. After filtration, the liquids were stored in five amber, plastic prescription bottles, and five amber, glass prescription bottles at 4°C and 23°C. The samples were collected at 0, 24, and 72 hours, and 1. 2, and 4 weeks after initiation of the study. Labetalol HCl was measured by an HPLC method. Because there was no substantial change in labetalol HCl concentration during the study period, the tablet dosage form can be reformulated, stored, and administered to elderly or pediatric patients as a liquid dosage form.
Urinary Retention—An Unusual Dystonic Reaction to Continuous Metoclopramide Infusion
Authors: Kohli-Kumar Mudra , Pearson Andrew D.J. , Sharkey Ian , Craft Alan W.
Published: June 2017

Vomiting is one of the most distressing adverse effects of cancer chemotherapy. Metoclopramide by continuous infusion (400 μg/kg/h after a loading dose of 2.5 mg/kg) is a novel administration method for optimizing efficacy. A two-year-old boy developed urinary retention on three occasions, once accompanied by priapism and slurred speech, while receiving a continuous infusion. This was reversed by procyclidine, suggesting that it may have been a dystonic reaction.
Idarubicin: A Second-Generation Anthracycline
Authors: Fields Suzanne M. , Koeller Jim M.
Published: June 2017

Because of its in vitro activity in leukemic cell lines and Phase I studies of acute leukemia, Phase II and III clinical trials with idarubicin hydrochloride were conducted in patients with acute lymphocytic leukemia or acute nonlymphocytic leukemia. In the Phase III comparative trials between the combinations of idarubicin and cytarabine and daunorubicin hydrochloride and cytarabine, the idarubicin/cytarabine combination resulted in significantly greater complete remission rates and longer overall survival in two of three studies conducted in the US. As a result, the Food and Drug Administration approved intravenous idarubicin with a Class 1A rating in September 1990 for use in combination with other antileukemic drugs (e.g., cytarabine) for the treatment of acute myelogenous leukemia in adults. The recommended dose of idarubicin is 12 mg/m2 daily for three days by slow intravenous injection in combination with cytarabine. Although idarubicin causes myelosuppression similar to that described with daunorubicin, the incidence of cardiotoxicity in animal models is lower. Idarubicin also has the advantage of oral administration, but the oral formulation of the drug remains investigational. The use of idarubicin in pediatric patients also remains to be established.
Effect of Age on Lymphocyte Beta2-Adrenergic Responsiveness
Authors: Rutledge David R. , Steinberg Joel D.
Published: June 2017

Beta-adrenergic receptor agonists and antagonists are among the most widely used classes of agents in the US today. Heterogeneity in pharmacologic response among humans exists. This article reviews the influence of age on lymphocyte beta2-adrenergic receptor responses. Evidence obtained in humans indicates that beta-adrenergic receptor numbers on peripheral blood cells may differ, although the direction of the change is not consistent among laboratories. Drug-induced regulation of receptors either up or down appears to be similar among age groups. The affinity of beta-adrenoceptor binding sites for isoproterenol decreases with aging. Events distal to the receptor recognition site itself exhibit age-related differences, presumably due to a decrease in the coupling of beta-adrenoceptors to adenylate cyclase. Mechanisms of decreased catecholamine responsiveness during aging remain to be defined. The precise definition of these alterations may contribute useful insights into the changes that occur with aging in response to catecholamines, other hormones, and neurotransmitters.
The Role of Corticosteroids in Infants and Children with Bacterial Meningitis
Authors: Reed Michael D. , Bahal Neeta , Nahata Milap C.
Published: June 2017

Bacterial meningitis continues to be a cause of substantial morbidity in infants and children. Hearing impairment is the most common sequela of this disease. Corticosteroids have been used in an attempt to reduce the incidence of meningitis-induced hearing loss. Some studies have demonstrated a decrease in the incidence of hearing impairment in patients treated with cefuroxime plus dexamethasone compared with cefuroxime alone. Similar data are lacking for other frequently used antibiotics. Based on these studies, the use of dexamethasone should be considered in infants and children greater than two months of age with suspected bacterial meningitis. Critical issues including the timing of steroid initiation in relation to antibiotic therapy and the appropriate antibiotic-corticosteroid regimen must be addressed. Studies should be performed to define the exact role of corticosteroids in the treatment of bacterial meningitis. Until additional data are available, we recommend the use of dexamethasone in pediatric patients older than two months of age with bacterial meningitis.
Evaluating the Cost Impact of Intravenous Antibiotic Dosing Frequencies
Authors: McGhan William F. , Bootman J. Lyle , Townsend Raymond J. , Foran Robert M. , Brett Judy L. , Wulf Patrick H.
Published: June 2017

Cost differences between antibiotic dosing frequencies were studied at Robert Wood Johnson University Hospital. Developing a complete cost profile between antibiotic alternatives is difficult because of role separation within the hospital. To present a more complete profile, the study analyzed the incremental costs associated with the hospital pharmacy and nursing staffs regarding various dosing frequencies, including different iv admixture and administration methods. Results showed that administration of an antibiotic dose costs approximately $3.35 based on labor and material costs associated with admixture and administration. An average of 4.6 minutes/dose saves nurses up to 23 minutes for each patient who receives an antibiotic dosed once rather than six times daily over a 24-hour period. Costs of administration and admixture should be considered in comparisons of combination therapy with monotherapy when deciding between two therapeutically equivalent alternatives.
Intravenous or Intramuscular Teicoplanin Once Daily for Skin and Soft-Tissue Infections
Authors: Edelstein Howard E. , Oster Sharon E. , Chirurgi Valerie A. , Karp Richard A. , Cassano Karen B. , McCabe Robert E.
Published: June 2017

Teicoplanin is a new glycopeptide antibiotic with potent activity against gram-positive bacteria and pharmacokinetics that allow once daily administration. To study the efficacy and safety of teicoplanin for skin and soft-tissue infections, 75 patients received teicoplanin intravenously (38) or intramuscularly (37, of which 16 were outpatients). Of 62 clinically evaluable patients, 97 percent of teicoplanin iv and 93 percent of teicoplanin im patients were cured or improved. All teicoplanin iv patients and 64 percent of teicoplanin im patients were cured microbiologically at 24–48 hours posttherapy. Persistence of organisms frequently was associated with skin ulcers or abscess cavities and usually had no bearing on clinical outcome. Possible adverse clinical and laboratory reactions caused by teicoplanin occurred in 4 of 38 teicoplanin iv patients (11 percent) and in 8 of 37 teicoplanin im patients (22 percent). Reactions were mild and resolved with discontinuation of teicoplanin in most cases. In this study, teicoplanin appeared to be safe, efficacious, and convenient for both hospital staff and patients, and potentially cost-effective for the treatment of skin and soft-tissue infections. In particular, teicoplanin appears to be appropriate for outpatient parenteral therapy.
Around the Beta-Blockers, One More Time
Authors: Sproat Thomas T. , Lopez Larry M.
Published: June 2017

We review the pharmacology, pharmacokinetics, and relative costs of beta-blockers, as well as indications for and therapeutic controversies surrounding their use. It is hoped that this discussion will assist clinicians in making informed decisions when choosing a drug for a hospital formulary or a particular patient. Beta-blockers are indicated for a variety of noncardiovascular and cardiovascular conditions, including hypertension, ischemic heart disease, arrhythmias, and prophylaxis of myocardial infarction (MI). These agents compete with catecholamines at beta-adrenoreceptors. They have different ancillary properties, including intrinsic sympathomimetic activity (ISA), cardioselectivity, and membrane stabilizing-activity, and vary in their duration of action, route of elimination, and lipophilicity. Beta-blocking agents decrease oxygen demand by exerting a negative inotropic and chronotropic effect. They also reduce blood pressure and possess antiarrhythmic effects. Beta-blockers penetrate the central nervous system (CNS) to different degrees and can cause a wide variety of CNS adverse effects. Nonselective beta-blockers have been noted to slightly reduce renal blood flow. Nadolol is an exception in that either no change, or even a small increase in renal blood flow, is observed upon initiation of therapy. Beta-blockers also act on the pulmonary bed by preventing beta2-mediated bronchodilation, thereby exacerbating bronchospastic disease in some patients. Beta-adrenergic blocking agents can potentiate both hypoglycemia and hyperglycemia in diabetic patients. Their effects on total peripheral resistance (TPR) are controversial. Initially it appears that beta-blockade increases TPR. After chronic therapy, however, TPR decreases to or below baseline values. These agents appear to be equally efficacious in the treatment of hypertension, arrhythmias, and ischemic heart disease. Agents with ISA should not be used for prevention of secondary MI. Cost may be the most practical differentiating factor when choosing agents for a hospital formulary or a particular patient.
Antiepileptic Medications in Development
Authors: Graves Nina M. , Leppik Ilo E.
Published: June 2017

Recently, there has been an increase in the research devoted to the study of investigational antiepileptic medications. This has led to extensive clinical trials of several new compounds. This review focuses on four of these antiepileptic medications in development: felbamate, gabapentin, lamotrigine, and vigabatrin. Each has a unique mechanism of action and great potential for the treatment of epilepsy.
Differences in Phenytoin Biotransformation and Susceptibility to Congenital Malformations: A Review
Authors: Reed Michael D. , Van Dyke Don C. , Berg Mary J. , Olson Carol H.
Published: June 2017

The clinical variability of teratogenic response to fetal drug exposure has been well documented. Metabolic differences in biotransformation have been shown to extend to multiple drugs and may involve many steps in drug metabolism with alterations of key intermediates. Although metabolic differences have been reported to be associated with complications of medication use, it has only recently been appreciated that such differences also may be associated in the unborn with the potential for the disruption of normal embryologic development and the production of congenital malformations. It has long been suspected that the teratogenicity of phenytoin may be mediated not only by the parent compound, but also by toxic intermediary metabolites that are produced during the biotransformation of the parent compound. Recent work elucidating differences in isoenzyme forms of cytochrome P-450 enzyme systems, glutathione, and microsomal epoxide hydrolase has provided increased interest in the multiple individual pharmacogenetic differences that may be significant factors affecting increased susceptibility to birth defects in individuals and families with fetal exposure to phenytoin.
The Effect of Renal Failure on Hepatic Drug Clearance
Authors: Touchette Mark A. , Slaughter Richard L.
Published: June 2017

It is known that loss of renal function decreases the hepatic clearance of some drugs, but the mechanisms by which this occurs are unclear. Knowledge of which drugs display reduced hepatic metabolism may be important for appropriate dosing of these drugs in uremic patients. Although no firm conclusions can be made regarding common pharmacokinetic and metabolic characteristics of drugs that display decreased hepatic metabolism in renal failure, certain observations deserve consideration. It appears that drugs metabolized by oxidation, conjugation, or both may be predisposed to decreased hepatic clearance in renal failure. Drugs that undergo oxidation by the P-450IID6 isozyme may be more likely to exhibit inhibition whereas those metabolized by the P-450IIIA4 isozyme may be spared. Future studies designed to clarify the mechanisms of decreased hepatic clearance in renal failure should take into account the multiplicity of P-450 enzymes for drugs that are oxidatively metabolized. The phenomenon of reduced hepatic drug clearance in uremia should be considered when evaluating the influence of renal failure on drug disposition.
Misperceptions and Inadequate Pain Management in Cancer Patients
Authors: Bressler Linda R. , Geraci Mark C. , Schatz Beth S.
Published: June 2017

This article examines misperceptions and barriers to adequate pain relief in cancer patients. Healthcare professionals have gaps in their knowledge of opioid drugs as well as misconceptions concerning tolerance, physical dependence, and addiction that often lead to the underprescribing of these agents. The pervasiveness of the “say no to drugs” message in our society and the fear of addiction on the part of patients and their families creates yet another barrier to the legitimate use of opioids to treat cancer pain. Legal and regulatory documents filled with arbitrary and ill-defined labels meant to promote the legitimate use of these drugs and curtail their misuse may instead intimidate healthcare professionals and negatively influence prescribing habits. Increased educational efforts for pharmacists and other healthcare professionals as well as the development of clinical role models and state cancer pain initiatives are cited as means to break down these barriers in order to achieve adequate pain relief for all cancer patients.
Mental Health in School-Aged Children Prenatally Exposed to Alcohol and Other Substances
Authors: Sandtorv Lisbeth Beate , Hysing Mari , Rognlid Malin , Nilsen Sondre Aasen , Elgen Irene Bircow
Published: June 2017

Prenatal exposure to substances can possibly influence a child’s neurodevelopment and may impact on subsequent mental health. We investigated the mental health status of school-aged children referred to a pediatric hospital with a history of prenatal exposure to alcohol or other substances. Mental health was assessed using the Strengths and Difficulties Questionnaire and compared with a reference group. A total of 105 of 128 (82%) eligible children prenatally exposed to substances participated in the study, with 48 children exposed to alcohol and 57 to other substances. Strengths and Difficulties Questionnaire subscale mean scores, total difficulties scores, and total impact scores were statistically significantly higher in the group of exposed children, compared with the reference group. In this hospital-based population of school-aged children prenatally exposed to alcohol or other substances, the exposed group had an increased risk of mental health problems, compared with the reference group.
An economic perspective on special events
Authors: Mules Trevor , Faulkner Bill
Published: June 2017

Special events are widely recognized as having a tourism impact and frequently form part of the tourism strategy of a country, or a destination region within a country. Governments in Australia and elsewhere have increasingly taken to funding such events as deliberate policies of tourism promotion and economic development. Australian examples are used to frame an approach to the economic evaluation of such policies. The analysis of economic impact of an event needs to identify clearly the region of interest, and the expenditure that is new to the region because of the event. A full evaluation should encompass social and promotional impacts. These are identifiable, but they are difficult to quantify.
Regional tourist organizations in Spain: emergence, policies and consequences
Authors: Pearce Douglas G.
Published: June 2017

As the result of the creation of autonomous communities in post-Franco Spain, a new regional level of public sector decision making and intervention in tourism was introduced. This paper examines the regional tourist organizations that emerged and shows how the major tourist regions developed separate, more flexible marketing bodies. Consideration is then given to recent policies and plans which have been developed largely in response to the crisis conditions of the late 1980s. These emphasize a need to improve competitiveness and set forth various related strategies to achieve this end. Consequences of this new level of intervention include increased attention to domestic tourism; creation of community tourism images, greater regional coverage and product diversification; and attempts to direct and control the growth of tourism through preparation and implementation of regional tourism plans.
Economic liberalization in India: opportunities for multinational corporations in the hospitality and tourism sector
Authors: Ahmed Zafar U. , Josiam Bharath M.
Published: June 2017

Multinational corporations (MNCs) in the hospitality and tourism sector have traditionally concentrated their global business operations on the more open and rewarding economies of the developed world. However, the contemporary global business environment has been fast changing in the post-Cold-War era. Asia's fast developing countries, such as India, are now offering enormous opportunities to MNCs. This paper offers a vision of what MNCs can do in order to incorporate India into their global expansion and diversification strategies. The paper gives an overview of the liberalized economic environment in India. It then identifies opportunities in the hospitality and tourism sector. It goes on to analyse the socio-economic factors that favour the entry of multinational corporations into the Indian hospitality and tourism sector.
Promoting transparency
Authors: Abuya Edwin O.
Published: June 2017

The right of access to information (ATI) is fundamental to any country that is governed by the rule of law. Indeed, there is a link between transparency and good governance, on the one hand, and ATI, on the other hand. The Constitution of Kenya recognizes this key entitlement. But Parliament was yet to pass comprehensive domestic law that would regulate this fundamental right. Notwithstanding this ‘gap’, courts have engaged with applications seeking information. Efforts by judges to flesh out the constitutional provision have led to the development of jurisprudence in this area of law in Kenya. This article shows that, while courts have made significant steps to operationalize the right of ATI in the country, basic legal steps have to be taken for this right to enjoyed fully. To conclude, the article makes specific recommendations.
The ill-informed
Authors: Cave Emma
Published: June 2017

Affirming the doctrine of informed consent, the UK Supreme Court in Montgomery v Lanarkshire HB belatedly followed the Australian decision of Rogers v Whitaker, decoupling the duty to inform patients about the material risks of medical treatment from Bolam. The underlying commitment to patient autonomy coincides with a wider body of medical law that protects the right of capacitous adult patients to make treatment decisions, even if others consider those decisions bizarre and even if they will cause the patient serious harm. It is seemingly anomalous, therefore, that the Supreme Court in Montgomery referred to a ‘therapeutic exception’ (TE), as this suggests an underlying paternalistic approach. Contrary to this view, international examples suggest that a TE does not necessarily conflict with commitment to patient autonomy. In some countries, the exception mitigates the effects of a broadly objective test of materiality by enabling clinicians in exceptional circumstances to protect the autonomy interests of the particular patient. In others, it protects those incapable of an autonomous decision from harm. In England and Wales, however, alternative mechanisms can be interpreted to protect such patients from harm. On this basis, it is argued that the TE is obfuscatory, unnecessary and unjustified.