bluuebunny/crossref_metadata_2025 huggingface dataset:
Globalisation and Raw Materials-Based Development: The Case of the Aluminum Industry
Authors: Ciccantell Paul S.
Published: January 2017

Current analyses of globalisation often assume that this is a new phenomenon and that it operates in the same manner across all sectors of the economy. This paper argues that precisely the opposite is true: globalisation is a longstanding process that exhibits distinct characteristics in different industries and different time periods. The analytic strategy to examine this process is historically grounded in the aluminum industry, one of the pioneers of the process of globalisation. This paper analyses the changing nature of the process of globalisation in the aluminum industry, focusing attention on the articulation of the competitive strategies of globalising firms and the economic development strategies of national governments over four distinct phases of globalisation in the past century. The paper also analyses the consequences of the evolution of globalisation for firms, states and economies involved in the aluminum industry.
Competition and Cooperation in Mediating the Global: The Case of Local Economic Development
Authors: Cox Kevin R. , Wood Andrew
Published: January 2017

The broad concern of this paper is the development of modes of cooperation in competitive contexts. The concrete vehicle for examining this is local economic development policy in the United States, in particular the projects of inward investment that have been its primary expression. This foregrounds the character of social organization as necessarily spatial organization: organization in this case for mediating inward investment. The paper shows how the socio-spatial contexts of agents result in problems of social integration and how they influence the particular forms of cooperative structure adopted in order to solve those problems.
The Globalization of Innovation, Nationalist Competition, and the Internationalization of Scientific Training
Authors: Carnoy Martin
Published: January 2017

Richard Gordon's work helps us understand that globalization of innovation does not diminish competition among states, but it does make it more difficult for states to influence the distribution of innovation rents. Yet, that doesn't keep states from trying. Gordon argued that they could be more successful if they cooperated rather than competed. This article claims that, whether they intend to or not, states do cooperate even as they are competing to expand their individual economic space. The cooperation occurs through the pervasive movement of science and engineering students and graduates from less innovative economies to more innovative economies and back, generally financed directly or indirectly by public funds. Public money in countries competing to get innovative rents mainly finances students to get their first degrees at home. But it also helps finance many to go to innovation centers for advanced degrees. Public money in the innovation centers finances university research and, in turn, graduate students to be trained doing the research. An increasing number of such students are from the hopeful competitors among the NICs. When foreign students stay in the innovation centers, states are implicitly “cooperating” to finance continued innovation in countries that can provide the most advanced training; when these graduates return to the less advanced innovating countries, states are implicitly “cooperating” to finance those countries' attempts to gain larger shares of innovation rents. The graduates, trained by developed country universities largely at developed states' expense and sometimes trained further as employees in developed country high-tech firms, are the most important resource in efforts to begin innovation efforts in the NICs. They also form a political force for promoting national innovation cores. So interstitial competition begets cooperation and interstatial cooperation can also beget competition.
Drug Use among Functionally Active, Aged, Ambulatory People
Authors: Delafuente Jeffrey C. , Meuleman John R. , Conlin Mary , Hoffman Nannette B. , Lowenthal David T.
Published: January 2017

BACKGROUND AND METHODS:

Only a few pharmacoepidemiology studies have included very old subjects and most studies included both healthy and very ill people. Interpretation of data from these investigations is limited because of the mix of health status in the populations studied. We examined drug use in a group of active, relatively healthy, older people. Sixty-one attendees at a national convention, aged 76–96 years, volunteered to participate in a study on health status in a very old, ambulatory population. Medication histories, selected blood biochemistry analyses, a mental status examination, and other data were collected.

RESULTS:

The mean number of prescription and nonprescription drugs used per person was 2.02 and 1.85, respectively. More than a quarter of the sample population took no prescription medications and two-thirds used two or fewer prescription drugs. Sixteen percent of those taking prescription medications experienced adverse effects from their current drug regimens. Although falling was prevalent among our study subjects, there were similar drug-use patterns in those who did and who did not fall.

CONCLUSIONS:

In a group of relatively healthy and functional very old people, we found that drug use was not excessive, although adverse effects were still prevalent. In addition, most subjects were knowledgeable about their medications. These studies demonstrate that extreme age alone does not always result in sickness, frailty, and overuse of medications.
Psychiatric Disturbances Associated with Ganciclovir Therapy
Authors: Chen Julie L. , Brocavich Joseph M. , Lin Anne Y.F.
Published: January 2017

OBJECTIVE:

To report a case of possible ganciclovir-induced psychiatric disturbances.

CASE SUMMARY:

A patient with AIDS who had no known psychiatric history and mild renal dysfunction experienced exacerbation of cytomegalovirus retinitis and was treated with ganciclovir 5 mg/kg iv q12h. The patient complained of nightmares and developed visual hallucinations and severe agitation on day 15 of ganciclovir therapy. The problems resolved after haloperidol administration and ganciclovir withdrawal and reappeared when the same regimen was reinstituted. However, the patient was able to tolerate the maintenance dose of ganciclovir at 5 mg/kg/d along with haloperidol later without further episodes of visual hallucinations.

DISCUSSION:

Case reports in the literature on ganciclovir- or its analog, acyclovir-, induced psychiatric disturbances were reviewed and compared. The potential relationship between ganciclovir accumulation in patients with renal insufficiency and the observed central nervous system problems in our patient was postulated.

CONCLUSIONS:

It is likely that ganciclovir accumulation contributed to the acute psychotic episodes observed in our patient. Adjusting ganciclovir dosage based on the patient's renal function is probably the only approach required to prevent or reduce the incidence of these episodes.
Naloxone-Associated Patient Violence: An Overlooked Toxicity?
Authors: Gaddis Gary M. , Watson William A.
Published: January 2017

OBJECTIVE:

To report two cases of a previously unreported adverse effect, violent patient behavior, after the reversal of sedation by intravenous naloxone.

DESIGN:

Case report.

PATIENTS/INTERVENTIONS:

Responses of two individuals who had reversal of sedation by intravenous naloxone are compared.

RESULTS:

Placement of patient restraints before the administration of intravenous naloxone to obtunded or unconscious patients can make an important contribution to the safety of patients, healthcare personnel, and public safety personnel, as illustrated by the violent reaction of one unrestrained patient after naloxone administration.

CONCLUSIONS:

Patient restraint should be considered before naloxone administration to protect the patient and healthcare workers. In the prehospital setting, limiting the use of naloxone to patients with decreased mental status and respiratory depression would decrease the likelihood of naloxone-induced violent behavior.
Danazol Increases the Anticoagulant Effect of Warfarin
Authors: Meeks Mimi L. , Mahaffey Kenneth W. , Katz Michael D.
Published: January 2017

OBJECTIVE:

To report two cases demonstrating an interaction between danazol and warfarin, resulting in the potentiation of warfarin's effect and bleeding complications.

DATA SOURCES:

Case reports, review articles, and studies identified by MEDLINE.

STUDY SELECTION:

All published English-language reports involving danazol and warfarin interactions were reviewed.

DATA SYNTHESIS:

Danazol, a synthetic testosterone derivative, is used in the treatment of endometriosis, fibrocystic breast disease, menorrhagia protein C deficiency, and hemophilia. We describe two cases including an interaction between danazol and warfarin, resulting in bleeding complications. There are at least two other reported cases of this interaction. This interaction may be attributable to several mechanisms. Danazol may inhibit the metabolism of warfarin and/or it may have a direct effect on the coagulation and fibrinolytic systems.

CONCLUSIONS:

Based on this report and other published cases, clinicians must be aware that danazol may increase the anticoagulant effect of warfarin. Patients receiving warfarin who are prescribed danazol must be monitored closely to prevent excessive anticoagulation and subsequent bleeding. Studies are needed to determine the frequency of this interaction and its underlying mechanisms.
Comparative Pharmacodynamics of Intravenous Lidocaine in Patients with Acute and Chronic Ventricular Arrhythmias
Authors: Hilleman Daniel E. , Mohiuddin Syed M. , Mooss Aryan N. , Hunter Claire B. , Destache Christopher J. , Sketch Michael H.
Published: January 2017

OBJECTIVE:

To evaluate the pharmacodynamics of intravenous lidocaine in patients with acute-onset and chronic ventricular arrhythmias.

DESIGN:

Open-label, pharmacodynamic evaluation.

SETTING:

Private, university-affiliated, hospital coronary-care unit.

PATIENTS:

Twenty cardiac patients with acute-onset ventricular ectopy and 20 with chronic ventricular ectopy.

INTERVENTIONS:

Intravenous lidocaine was administered to all patients as a 1-mg/kg bolus, a 0.5-mg/kg bolus, and a 2.8-mg/min constant infusion for 48 hours.

MAIN OUTCOME MEASURES:

Changes in ventricular premature beat (VPB) frequency against total treatment period frequency and by an hour-to-hour assessment of changes in VPB frequency compared with total baseline frequencies. Response was defined as ≥80 percent total VPB reduction, ≥90 percent paired VPB reduction, and total abolition of nonsustained ventricular tachycardia events.

RESULTS:

A statistically significant difference in the pharmacodynamic effects of lidocaine were observed during the first eight hours of treatment in patients with acute-onset and chronic VPBs. The number of patients with acute-onset VPBs who responded to lidocaine in the first hour of treatment did not change significantly over the remaining hours of treatment. Response to lidocaine was less in patients with chronic VPBs than in patients with acute-onset VPBs. The response rate to lidocaine was significantly less during the first eight hours in patients with chronic VPBs than in patients with acute-onset VPBs. Following eight hours of treatment, the response rates between acute-onset and chronic VPB patients were not significantly different. Mean lidocaine plasma concentrations were not different between the groups. In addition, there were no significant differences in the incidence of adverse effects between the two groups.

CONCLUSIONS:

The onset of antiarrhythmic effect as measured by suppression of ventricular ectopy is delayed in patients with chronic VPBs compared with patients with acute-onset VPBs. Decisions about lidocaine response in patients with chronic VPBs cannot be made accurately in the first eight hours of therapy.
Stability of Ondansetron in Large-Volume Parenteral Solutions
Authors: Graham C. Lynn , Dukes George E. , Kao Cheng-Fang , Bertch Jeanne M. , Hak Lawrence J.
Published: January 2017

OBJECTIVE:

To determine the stability of ondansetron hydrochloride in large-volume parenteral solutions under four storage and time-period conditions.

DESIGN/METHOD:

Ondansetron was added to each of the following commercially available solutions to make final concentrations of approximately 24 and 96 μg/mL: NaCl 0.9%, D5W, and lactated Ringer's solution.

SETTING:

University analytical laboratory.

MAIN OUTCOME MEASURES:

Each solution was studied at both concentrations under the following conditions: (1) 1 day refrigerated, 2 days room temperature; (2) 7 days refrigerated, 2 days room temperature; (3) 14 days refrigerated, 2 days room temperature; and (4) 14 days room temperature. All solutions were exposed to fluorescent light when under room temperature conditions and were studied in triplicate. Ondansetron concentrations of samples were obtained periodically throughout each storage/time condition via a specific, stability-indicating HPLC method.

RESULTS:

A clinically significant loss of concentration was defined as >10 percent decrease from the initial concentration. In all solutions and at both concentrations studied, the mean ondansetron concentration was ≥90 percent under all storage and time conditions.

CONCLUSIONS:

Ondansetron can be stored and administered in these solutions without loss of potency.
Sumatriptan: A Selective 5-Hydroxytryptamine Receptor Agonist for the Acute Treatment of Migraine
Authors: Fullerton Terence , Gengo Fran M.
Published: January 2017

OBJECTIVE:

The clinical pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and associated drug interactions of the novel antimigraine drug sumatriptan are reviewed.

DATA SOURCES:

English-language publications pertaining to sumatriptan were identified via a search of the MEDLINE computerized database.

STUDY SELECTION:

Open and controlled clinical studies were reviewed in assessing clinical efficacy, although only the results of controlled, randomized trials form the basis for the conclusions pertaining to the effectiveness of sumatriptan.

DATA EXTRACTION:

The primary measure of drug effectiveness in all clinical studies was significant improvement in headache severity scores. Secondary measures included functional ability, time to relief, rescue medication use, associated symptoms of nausea/vomiting and photo/phonophobia, and, in some studies, headache recurrence rate. These data were obtained from each published clinical trial and used in the overall analysis of sumatriptan efficacy.

DATA SYNTHESIS:

Sumatriptan is a serotonin agonist that has been studied for the acute treatment of migraine and cluster headache. The drug appears to work via specific serotonin receptors to mediate selective vasoconstriction within the cranial vasculature and to prevent the release of inflammatory mediators from trigeminal nerve terminals. The recommended dose of sumatriptan is 6 mg given subcutaneously at the onset of headache; an oral formulation is under investigation. In the published clinical trials of the oral and subcutaneous dosage forms to date, sumatriptan was effective in reducing headache severity from moderate/severe to mild/absent in approximately 70–80 percent of patients treated with active drug, compared with only 20–30 percent in the placebo groups, and 48 percent in the oral ergotamine tartrate/caffeine (Cafergot)-treated group. Secondary measures of effectiveness also favored sumatriptan. There may be a higher rate of headache recurrence with sumatriptan compared with placebo or Cafergot, although further study is necessary to confirm this observation. Adverse effects associated with sumatriptan administration generally were mild and transient and included tingling, warm/hot sensations, and pressure and tightness in the chest and neck. No significant drug interactions have yet been identified.

CONCLUSIONS:

Sumatriptan appears to represent a safe and effective alternative to the ergot alkaloids for the abortive treatment of acute migraine. However, further clinical trials, especially those yielding comparative data with current antimigraine agents, are needed to determine the full therapeutic contribution of sumatriptan.
Cloxacillin-Induced Acute Tubulo Interstitial Nephritis
Authors: García-Ortiz Roberto , Espinoza Roberto S. , Silva Gonzalo R. , Alonso Rodrigo K. , Opazo Hector S. , Houghton Donald C.
Published: January 2017

OBJECTIVE:

To report a case of possible cloxacillin-induced acute tubulo interstitial nephritis (AIN).

CASE SUMMARY:

A 15-year-old male patient presented with hypertension, edema, lumbar pain, sterile pyuria, eosinophiluria (ten percent), and severe renal dysfunction three months after the ingestion of cloxacillin. A renal biopsy revealed diffuse edema and inflammatory infiltrate of the interstitium (five percent eosinophils). He received four sessions of peritoneal dialysis with dramatic improvement in urinary output and renal function. His biochemical parameters returned to normal values 21 days after admission, without the use of glucocorticosteroids.

DISCUSSION:

Published case reports on AIN induced by penicillin and related drugs are reviewed and compared. The role of interstitial edema in acute renal failure associated with drug-induced AIN is mentioned.

CONCLUSIONS:

AIN is a rare but significant complication of therapy with penicillin and related drugs. The clinical picture is similar for all of these drugs, but skin rash and fever are absent in AIN induced by cloxacillin and cloxacillin-related drugs. Dialysis improved the patient's urinary output and renal function. Beta-lactam antibiotics should be avoided in patients with cloxacillin-induced AIN.
Effect of Histamine H2-Receptor Antagonists on Vitamin B12 Absorption
Authors: Force Rex W. , Nahata Milap C.
Published: January 2017

OBJECTIVE:

To discuss the potential of histamine H2-receptor antagonists (H2RAs) to cause malabsorption of vitamin B12 (cyanocobalamin).

DATA SOURCES:

Pertinent literature was identified via a MEDLINE search. Journals and references cited in published articles also were used as data sources.

STUDY SELECTION:

Studies evaluating the effect of H2RAs on vitamin B12 absorption were reviewed.

DATA SYNTHESIS:

H2RAs decrease acid secretion by the gastric parietal cells. Gastric acid and pepsin produced by these cells are required for the cleavage of vitamin B12 from dietary sources. Intrinsic factor (IF), also produced by gastric parietal cells, is required for vitamin B12 absorption from the gastrointestinal tract. Although H2RAs have not conclusively been shown to decrease IF secretion, studies have demonstrated a significant reduction in food-bound vitamin B12 absorption secondary to decreased acid secretion in patients taking these drugs.

CONCLUSIONS:

H2RAs have the potential to cause vitamin B12 deficiency. This may be important in patients with inadequate stores of vitamin B12 (e.g., poor diet), particularly those receiving H2RA therapy continuously for more than two years. Healthcare providers should be aware of this potential adverse effect.
Pharmacokinetics of Zidovudine and Acetaminophen in a Patient on Chronic Acetaminophen Therapy
Authors: Burger David M. , Meenhorst Pieter L. , Koks Cornells H.W. , Beijnen Jos H.
Published: January 2017

OBJECTIVE:

To report a case of a potential interaction between acetaminophen and zidovudine in a patient who had used high daily doses of acetaminophen over many years.

CASE SUMMARY:

A 43-year-old man presented with HIV-1 infection, recurrent oral candidiasis, and chronic use of acetaminophen, codeine, and diazepam before he started zidovudine therapy. Although literature was available regarding short-term combined use of acetaminophen and zidovudine, information was lacking on zidovudine therapy and kinetics after long-term use of acetaminophen. Acetaminophen and zidovudine pharmacokinetics were determined on several occasions. The results showed extremely rapid absorption of both drugs (tmax, the time to reach maximum concentration. 10–15 minutes for acetaminophen and 15–20 minutes for zidovudine) and, consequently, relatively high maximum plasma concentration (Cmax). No influence on other pharmacokinetic parameters of either drug could be detected. Because the effect of high Cmax values of zidovudine is unknown, the patient was treated with a third of the dose of zidovudine used at that time (zidovudine 100 mg q6h). No toxicity or opportunistic infections developed within the next 8 months, after which the patient died of a cause unrelated to HIV infection.

DISCUSSION:

The observed pharmacokinetic profiles of both drugs are discussed and compared with two studies dealing with zidovudine therapy in combination with short-term use of acetaminophen and with a case report of acetaminophen-induced hepatotoxicity during concomitant use of zidovudine.

CONCLUSIONS:

Long-term use of acetaminophen may accelerate the absorption of zidovudine. Although other causes cannot be ruled out, there was no influence on other pharmacokinetic parameters of zidovudine. No influence of zidovudine on acetaminophen concentrations was found. Combined use of zidovudine 100 mg q6h and acetaminophen 500 mg q4h appeared to be safe and effective for at least eight months.
Oral Antihypertensives for Hypertensive Urgencies
Authors: Gales Mark A.
Published: January 2017

OBJECTIVE:

To review the data describing the use of oral antihypertensive agents in the treatment of hypertensive urgencies (HU).

DATA SOURCES:

A MEDLINE search of the English-language literature and fan searches of papers evaluating oral antihypertensives in HUs and emergencies were conducted.

STUDY SELECTION:

Controlled and uncontrolled studies in humans are reviewed. Emphasis was placed on recent trials evaluating individual agents and comparative trials.

DATA SYNTHESIS:

Comparative trials have demonstrated that four currently available oral agents can lower blood pressure rapidly and predictably. Nifedipine, the most extensively studied, and clonidine have served traditionally as the oral agents of choice for the treatment of HUs. All the agents can lower blood pressure effectively within the first few hours after dosing, but their use also has been associated with adverse effects. Nifedipine and captopril are the two agents with the most rapid onset, within 0.5–1 hour, and may treat hypertensive emergencies as well as urgencies. Clonidine and labetalol have maximal blood pressure lowering effects at 2–4 hours.

CONCLUSIONS:

Captopril, clonidine, labetalol, and nifedipine are all effective agents for the treatment of HUs. Agent selection should be based on the perceived need for urgent blood pressure control, the cause of HU, and concomitant conditions. A definite benefit from acute blood pressure lowering in HUs has yet to be demonstrated, especially in asymptomatic patients. More controlled trials with less aggressive dosing regimens and placebo controls need to be performed to assess the most appropriate treatments for HUs with the fewest adverse effects.
Neurologic Sequelae Associated with Foscarnet Therapy
Authors: Lor Edward , Liu Yong Qing
Published: January 2017

OBJECTIVE:

To report three cases of possible foscarnet-induced neurologic sequelae.

CASE SUMMARY:

We report two cases of seizures and one case of hand cramping and finger paresthesia after starting foscarnet therapy with no evidence of predisposing risk factors, such as serum laboratory abnormalities, renal dysfunction, or known central nervous system (CNS) involvement. All three patients had stable laboratory values during therapy and when the neurologic adverse effects occurred. All patients were receiving appropriate dosages of foscarnet.

DISCUSSION:

The incidence of seizures in AIDS patients was reviewed. A history of CNS lesions, infections, and/or AIDS per se may increase the risk of a neurologic adverse effect while receiving foscarnet therapy. Acute ionized hypocalcemia may cause these neurologic adverse effects. Ionized hypocalcemia is transitory, is related to the rate of foscarnet infusion, and may not be reflected as a change in total serum calcium concentration.

CONCLUSIONS:

Foscarnet probably contributed to the neurologic adverse effects reported here. Foscarnet may need to be administered at a slower rate than is recommended by the manufacturer. Electrolytes must be monitored closely; however, a neurologic adverse effect may not be foreseen.
Dexrazoxane in the Prevention of Doxorubicin-Induced Cardiotoxicity
Authors: Seifert Charles F. , Nesser Mary Ellen , Thompson Dennis F.
Published: January 2017

OBJECTIVE:

To review doxorubicin-induced cardiotoxicity and to evaluate the use of dexrazoxane in its prevention.

DATA SOURCES:

All animal and human reports involving doxorubicin-induced cardiac adverse effects were searched using MEDLINE combined with a fan search of relevant papers.

DATA EXTRACTION:

Animal, in vitro cellular, and human data are thoroughly reviewed with particular emphasis on doxorubicin-induced cardiotoxicity, including clinical manifestations, risk factors, and mechanisms of toxicity. The role of dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity is reviewed, including mechanism of effect, animal data, and human trials.

DATA SYNTHESIS:

Anthracyclines are associated with a cumulative, dose-dependent, irreversible cardiomyopathy that can lead to congestive heart failure and death. The incidence of cardiotoxicity rises sharply at a total lifetime dose of more than 550 mg/m2. Through its semiquinone metabolite, doxorubicin appears to generate superoxide anion and superhydroxide free radicals with iron as a cofactor. Because of poor myocardial concentrations of superoxide dismutase, catalase, and glutathione peroxidase, these free radicals cause extensive lipid peroxidation and mitochondrial destruction.

CONCLUSIONS:

Dexrazoxane is hydrolyzed to its active form intracellularly and binds iron to prevent the formation of superhydroxide radicals, thus preventing mitochondrial destruction. The effect of dexrazoxane on the prevention of doxorubicin-induced cardiotoxicity is impressive in both animal and human studies. Further research is needed to clearly demonstrate the effect dexrazoxane has on the antitumor effects of combination chemotherapy while defining optimal dosing strategies to minimize myelosuppression and maximize cardioprotection.
Chronic Suppurative Otitis Media
Authors: Reed Michael D. , Wintermeyer Susan M. , Nahata Milap C.
Published: January 2017

OBJECTIVE:

To review various aspects of chronic suppurative otitis media (CSOM).

DATA SOURCES:

A MEDLINE search and extensive review of articles provided the information for this review.

DATA EXTRACTION:

Studies describing the epidemiology, microbiology, risk factors, pathology, diagnosis, treatment, complications, and recurrence of CSOM were included.

DATA SYNTHESIS:

Pseudomonas aeruginosa and anaerobes are the most predominant bacteria found in CSOM. Treatment with otic, oral, or parenteral drugs (e.g., neomycin/polymyxin B/hydrocortisone otic, ciprofloxacin, ceftazidime, or aminoglycosides) should be guided by ear fluid culture results. Prompt treatment with effective and safe antibiotics may prevent complications of CSOM.

CONCLUSIONS:

Treatment of CSOM has improved as a result of availability of effective otic and oral antibiotics. Treatment of the anaerobic infection with antibiotics should be studied further.
Adenosine Use in Pregnant Women with Supraventricular Tachycardia
Authors: Hagley Michael T. , Cole Patricia L.
Published: January 2017

OBJECTIVE:

To review a case experience and published reports of treatment of supraventricular tachycardia with adenosine in pregnant women.

DATA SOURCES:

Published reports and clinical experience.

DATA SYNTHESIS:

Seven pregnant women with supraventricular tachycardia treated with adenosine have been described in the literature. We describe an eighth patient. Treatment has terminated the dysrhythmia in all cases, and no adverse maternal or fetal effects have been reported.

CONCLUSIONS:

Based on theoretical considerations and on limited published experience, adenosine appears to be safe and effective for treatment of supraventricular tachycardia in pregnant patients.
Assessment of Chemotherapy-Induced Emesis and Evaluation of a Reduced-Dose Intravenous Ondansetron Regimen in Pediatric Outpatients with Leukemia
Authors: Holdsworth Mark T. , Raisch Dennis W. , Duncan Marilyn H. , Chavez Cathy M. , Leasure Mary M.
Published: January 2017

Objective:

To measure the severity of nausea and vomiting in pediatric patients receiving intravenous or intrathecal chemotherapy for acute lymphoblastic leukemia and to evaluate the effectiveness of 2 intravenous doses of ondansetron for this condition.

Design:

Patients were surveyed during repeated treatments of maintenance chemotherapy, given with or without ondansetron, using a repeated measures pretest/posttest design.

Setting:

Outpatient pediatric oncology clinic.

Patient population:

Sixteen pediatric patients (aged 2–15 years, mean 6.2) with acute lymphoblastic leukemia.

Methods:

Surveys to assess nausea and vomiting and the extent of interference with daily activities were administered following emetogenic chemotherapy with or without ondansetron.

Results:

A total of 255 surveys following emetogenic chemotherapy with daunorubicin, cyclophosphamide, carmustine, and etoposide and cytarabine combined, as well as intrathecal therapy with methotrexate, hydrocortisone, and cytarabine, were analyzed. Analysis was performed on surveys of 149 courses without antiemetic therapy and 106 courses after 2 doses of ondansetron 0.15 mg/kg iv. The most emetogenic chemotherapy treatment was the etoposide/cytarabine combination (p<0.05). Ondansetron completely protected patients (defined as no nausea or no vomiting) during most (>50%) of the chemotherapy treatments, except for those in which cyclophosphamide was used. Ondansetron provided greater control of nausea and vomiting, a higher percentage of complete protection, and decreased the daily activity interference rating for carmustine and etoposide/cytarabine compared with courses of chemotherapy without antiemetics (p<0.05). Two intravenous doses of ondansetron also provided durable antiemetic efficacy over time for the most emetogenic chemotherapy treatment (etoposide/cytarabine).

Conclusions:

Etoposide/cytarabine proved to be the most emetogenic of the chemotherapy treatments studied. A reduced-dose regimen of intravenous ondansetron was shown to be an effective antiemetic for the outpatient treatments with etoposide/cytarabine and carmustine, but not with cyclophosphamide.
Tissue Necrosis and Necrotizing Fasciitis After Intramuscular Administration of Diclofenac
Authors: Pillans Peter I. , O'Connor Nanette
Published: January 2017

Objective:

To report 6 cases of severe local reactions associated with intramuscular injection of diclofenac.

Case Summaries:

Three patients developed extensive tissue necrosis at the injection site after intramuscular diclofenac. Necrotizing fasciitis in an additional 3 patients was associated with complications such as adult respiratory distress syndrome, renal failure, shock, and disseminated intravascular coagulation. Organisms were cultured from the necrotic site in 3 cases. Two patients died.

Discussion:

Tissue necrosis is a rare but serious complication of intramuscular administration of medicines, including nonsteroidal antiinflammatory drugs (NSAIDs). Pain often occurs at the time of the injection, but tissue necrosis typically becomes apparent a few days later. Necrotizing fasciitis is characterized by rapidly spreading infection with necrosis of fascia and subcutaneous fat.

Conclusions:

Intramuscular administration of diclofenac may be associated with severe tissue necrosis or necrotizing fasciitis. Although rare, these serious complications should be considered when intramuscular injection of NSAIDs is contemplated.
Effects of Recombinant Human DNase Therapy on Healthcare use and Costs in Patients with Cystic Fibrosis
Authors: Oster Gerry , Huse Daniel M , Lacey Michael J , Regan Meredith M , Fuchs Henry J
Published: January 2017

Objective:

To assess the effects of recombinant human DNase (rhDNase) therapy on the cost of treating respiratory tract infections (RTIs) in patients with cystic fibrosis.

Design:

We prospectively documented the use of healthcare services among 968 patients with cystic fibrosis who participated in a recent Phase III double-blind, multicenter, clinical trial in which patients were assigned randomly to receive either rhDNase 2.5 mg once daily, rhDNase 2.5 mg twice daily, or placebo. All patients were followed for 24 weeks. Data from secondary sources were used to estimate a total cost of RTI-related care (excluding the cost of study therapy) for each trial participant, based on observed levels of resource use.

Main Outcome Measures:

Number of RTI-related hospital admissions, days of RTI-related outpatient antibiotic therapy (intravenous and oral), and total costs of RTI-related care (excluding the cost of study therapy).

Results:

Patients randomized to receive rhDNase once daily averaged 0.15 fewer RTI-related hospital admissions (0.41 vs 0.56 for placebo; p < 0.05) and 1.5 fewer days of RTI-related outpatient intravenous antibiotic therapy (2.9 vs 4.4; p < 0.05). Patients randomized to receive rhDNase twice daily had 0.14 fewer hospital admissions (p < 0.01), but no reduction in outpatient intravenous antibiotic therapy. Compared with placebo, the cost of treating RTIs over 24 weeks was $814–1682 less among patients receiving rhDNase.

Conclusions:

rhDNase therapy reduced the costs of treating RTIs in patients with cystic fibrosis; assuming once-daily dosing, these savings would offset about one-third of the cost of such therapy.
Delirium Probably Induced by Clarithromycin in a Patient Receiving Fluoxetine
Authors: Pollak P Timothy , Sketris Ingrid S , MacKenzie Susan L , Hewlett Thomas J
Published: January 2017

Background:

Clarithromycin is a macrolide antibiotic very similar to erythromycin in structure and spectrum of activity. It has gained increasing use since its release in Canada in May 1992, partly because it is promoted as having less potential for drug interactions and adverse effects. However, as with all new medications, a high degree of vigilance for unreported adverse effects is advisable.

Case Summary:

A healthy 53-year-old lawyer was receiving long-term fluoxetine 80 mg hs and nitrazepam 10 mg hs for depression and mild sleep apnea. Subsequent to initiation of treatment with clarithromycin for a respiratory infection, he rapidly developed delirium, which cleared quickly after stopping all 3 medications. The delirium and psychosis did not recur when the infection was treated with erythromycin alone or after restarting fluoxetine and nitrazepam therapy at previous dosages in the absence of antibiotics.

Discussion:

This man's delirium is consistent with fluoxetine intoxication, which appears to have resulted from inhibition of hepatic cytochrome P450 metabolism by clarithromycin. Undiagnosed, this serious drug reaction could have lead to serious medical and social consequences.

Conclusions:

As the use of clarithromycin increases, the potential for interactions with other drugs metabolized by the P450 enzyme system may be realized. Clinicians should consider which other medications a patient is receiving before prescribing clarithromycin or any macrolide antibiotic with potential to influence the P450 system.
Impact of Preexisting Health Conditions on the Outcome of an Adverse Drug Reaction Alerting Program: Gastrointestinal Disorders Before Piroxicam and Sulindac Therapy
Authors: Rawson Nigel SB
Published: January 2017

Objective:

To assess the impact of data concerning preexisting serious gastrointestinal (GI) disorders before piroxicam and sulindac therapy in an acute adverse drug reaction alerting program.

Design:

Cohort study.

Setting:

Saskatchewan province's prescription drug and healthcare insurance system covering a population of approximately 1 million.

Participants:

The first 20 000 new patients who were dispensed piroxicam in 1982 and the first 20 000 patients who were dispensed sulindac in 1979-1981 through the Saskatchewan drug plan.

Main Outcome Measures:

Physician services and hospitalizations with a diagnosis of peptic ulceration or GI hemorrhage within 30 days of the first piroxicam or sulindac prescription.

Results:

Rates of physician services for peptic ulceration or GI hemorrhage in the 30 days after starting piroxicam or sulindac therapy for patients who had services or hospitalizations for serious stomach or duodenum disorders in the 90 days before their prescriptions were significantly greater than the corresponding rates for patients without a recent history of these conditions (piroxicam: odds ratio [OR] = 7.89; 95% confidence interval [CI] =5.71 to 10.91; p> 0.001; sulindac: OR = 24.08; 95% CI = 18.99 to 30.54; p < 0.001). Also, the rate of hospitalizations for peptic ulceration or GI hemorrhage in the 30 days after starting sulindac therapy for patients who had services for the conditions in the previous 90 days was significantly greater than the rate for patients who did not (OR = 10.91; 95% CI = 5.70 to 20.87; p> 0.001).

Conclusions:

Rates of serious GI disorders in patients taking piroxicam and sulindac with a recent history of such disorders were larger than those in the other patients. However, because the proportion of individuals with recent serious GI disorders is small, these differences are lost in an overall assessment of patients taking these drugs. Data regarding preexisting health conditions are essential in adverse drug reaction alerting programs and, indeed, in all evaluations of adverse reactions.
Use of Haloperidol Infusions to Control Delirium in Critically Ill Adults
Authors: Seneff Michael G , Mathews Renia A
Published: January 2017

Objective:

To describe and discuss the use of continuous intravenous infusions of Haloperidol to treat severe delirium and agitation in 3 intensive care unit (ICU) patients.

Case Summaries:

Three severely agitated patients in ICU did not respond to conventional therapy with opiates, benzodiazepines, and intermittent intravenous doses of haloperidol. In each case, control was achieved rapidly after initiation and titration of a continuous haloperidol infusion. Two patients had a history of schizophrenia. No adverse effects attributable to therapy were identified.

Discussion:

Haloperidol is often used in the ICU for control of severe agitation, even in patients without a psychiatric history. It usually is given by bolus intravenous injection, sometimes in high doses (>5 mg), even though that is not approved by the Food and Drug Administration. Intravenous haloperidol is generally well tolerated, but multiform ventricular tachycardia has been reported. Experience with continuous haloperidol infusions is growing, and it appears to be an effective method for control of severe agitation or delirium. In our experience and in other limited published data, adverse effects are rare, but prolongation of the QT interval has occurred and multiform ventricular tachycardia is likely a risk.

Conclusions:

In selected patients, a continuous infusion of haloperidol may be a useful alternative for control of agitation and delirium. Close monitoring for QT prolongation or rhythm disturbances is mandatory.
Phenytoin-Folic Acid Interaction
Authors: Lewis Dale P , Van Dyke Don C , Willhite Laurie A , Stumbo Phyllis J , Berg Mary J
Published: January 2017

Objective:

To review information regarding the dual and interdependent drug-nutrient interaction between phenytoin and folic acid and other literature involving phenytoin and folic acid.

Data Sources:

Information was retrieved from a MEDLINE search of English-language literature conducted from 1983 (time of the last review) to March 1995. Search terms included folic acid, phenytoin, and folic acid deficiency. Additional references were obtained from Current Contents and from the bibliographies of the retrieved references.

Study Selection:

All human studies examining the effects of phenytoin on serum folate concentrations and folic acid supplementation on serum phenytoin concentrations were selected. These included studies of patients with epilepsy and healthy volunteers as well as case reports. Case reports were included because of the extensive length of time needed to study this drug interaction.

Data Extraction:

Data extracted included gender, dosing, serum folate concentrations if available, pharmacokinetics, and adverse events.

Data Synthesis:

Serum folate decreases when phenytoin therapy is initiated alone with no folate supplementation. Folic acid supplementation in folate-deficient patients with epilepsy changes the pharmacokinetics of phenytoin, usually leading to lower serum phenytoin concentrations and possible seizure breakthrough. Folate is hypothesized to be a cofactor in phenytoin metabolism and may be responsible for the “pseudo-steady-state,” which is a concentration where phenytoin appears to be at steady-state, but in reality, is not. Phenytoin and folic acid therapy initiated concomitantly prevents decreased folate and phenytoin obtains steady-state concentrations sooner.

Conclusions:

Folic acid supplementation should be initiated each time phenytoin therapy commences because of the hypothesized cofactor mechanism, decreased adverse effects associated with folate deficiency, and better seizure control with no perturbation of phenytoin pharmacokinetics.
Multiple Delayed Peak Lithium Concentrations following Acute Intoxication with an Extended-Release Product
Authors: Dupuis Robert E , Cooper April A , Rosamond Laura J , Campbell-Bright Stacy
Published: January 2017

OBJECTIVE:

To describe delayed peak lithium concentrations after an overdose of extended-release lithium tablets.

CASE SUMMARY:

a patient with borderline personality disorder and depression ingested extended-release lithium approximately 20.25 g along with other agents. At presentation, the lithium concentration was 1.4 mEq/L. Significant enteral intake was initiated 27 hours after presentation and the lithium concentration 5 hours later increased to 3.2 mEq/L. A second lithium peak concentration of 5.0 mEq/L was noted 40 hours after presentation. Two hemodialysis sessions lasting 4 hours each were performed along with administration of sodium polystyrene sulfonate in sorbitol 20% to enhance lithium elimination and decrease absorption. Eighty-eight hours after presentation, the lithium concentration had decreased to 1.5 mEq/L.

DISCUSSION:

Delayed and secondary peak lithium concentrations have been reported following an overdose with an extended-release product. Extended-release lithium may form an aggregate in the gastrointestinal tract and/or have delayed absorption secondary to coingested drugs. Toxicity may result if the patient begins enteral intake of drugs, fluids, or nutrition.

CONCLUSIONS:

Continued monitoring of lithium concentrations after an acute ingestion with an extended-release product are recommended until lithium concentrations are less than 1.5 mEq/L and there are no signs of toxicity, particularly once the patient begins significant enteral intake.
The Asthma Year in Swedish Pharmacies: A Nationwide Information and Pharmaceutical Care Program for Patients with Asthma
Authors: Lisper Britta , Nilsson J Lars G
Published: January 2017

OBJECTIVE:

TO increase the understanding of asthma among patients and the general public in Sweden and to increase the collaboration among healthcare personnel for the benefit of asthma patients.

DESIGN:

Based on the results from problem detection studies, Apoteksbolaget the national organization for pharmacies in Sweden, designed a program to educate healthcare professionals and the public about asthma. Entitled the “Asthma Year,” all pharmacy staffs were offered education on asthma, patients were provided written information and audiovisual materials, and the general public was made more aware of asthma through local media.

SETTING:

Pharmacies, healthcare centers, hospital outpatient areas, libraries, places of work, and domestic airports.

PARTICIPANTS:

All pharmacy staffs (12 000 persons) were offered an education on asthma. Patients with asthma were offered brochures and leaflets in pharmacies and information in the pharmacy magazine Apoteket. The general public received information about asthma through posters, radio, and television.

MAIN OUTCOME MEASURES:

The evaluations of the Asthma Year indicate that the activities had an impact on the public, on patients with asthma, and on the pharmacy staffs.

RESULTS:

About 4.5 million people in Sweden (42% of the population) observed the Asthma Year or received information about asthma, and 49% of the patients learned something new about their disease. Twice as many patients used steroid therapy regularly after the campaign than before. Of the pharmacy staffs, 96% were favorable to the idea of working with campaign years and 85% believed that they were personally involved with the activities.

CONCLUSIONS:

Patient outcomes in terms of reduced morbidity have not been possible to document, but the number of deaths from asthma in Sweden decreased from 438 during the previous year to 398 during the Asthma Year.
Possible Erythromelalgia-Like Syndrome Associated with Nifedipine in a Patient with Raynaud's Phenomenon
Authors: Sunahara Janice Fong , Gora-Harper Mary Lea , Nash Kimberly Suzanne
Published: January 2017

OBJECTIVE:

TO describe a patient who was diagnosed with Raynaud's phenomenon, was prescribed immediate-release nifedipine, and developed a possible erythromelalgia-like syndrome.

CASE SUMMARY:

A 24-year-old white woman with a history of esophageal spasms and Raynaud's phenomenon was prescribed nifedipine 10 mg po qid. Approximately 1 hour after the patient had taken the fourth dose of nifedipine, she experienced acute erythema and a burning sensation in her feet and lower limbs, light-headedness, and palpitations. Because of a reportedly abnormally low blood pressure, the patient took diphenhydramine 50 mg po and proceeded to the clinic. On arrival, abnormal vital signs were BP 140/48 mm Hg and HR 130 beats/min. Without any other medical intervention, approximately 30 minutes later her blood pressure and heart rate had returned to baseline at 122/60 mm Hg and 96 beats/min, respectively. The nifedipine was permanently discontinued and the patient's symptoms completely resolved over 24 hours.

DISCUSSION:

The characteristic symptoms of erythromelalgia include burning pain, increased skin temperature, and erythema of the extremities, usually to the feet, lower legs, and, less often, the hands. Erythromelalgia-like syndromes secondary to the administration of many medications have been reported. Several nifedipine-related reports describe an erythromelalgia-like syndrome similar to our reported case.

CONCLUSIONS:

Because the patient was not taking any other medications and the symptoms started with the administration of nifedipine and were relieved after its discontinuation, nifedipine was thought to be the cause of the erythromelalgia-like syndrome.
Sulfadiazine-Induced Sialadenitis
Authors: Añíbarro Belén , Fontela Jose L
Published: January 2017

OBJECTIVE:

To present a case of sialadenitis induced by sulfadiazine.

CASE SUMMARY:

A 50-year-old man with bronchitis developed swelling of the parotid glands and floor of the mouth as well as plugging in his ears 2 hours after ingestion of Bronco-aseptilex (sulfadiazine, cyclamate, and guaiacol). Skin-prick tests performed with serial dilutions of sulfadiazine and Bronco-aseptilex were all negative. We then performed oral challenge tests with Bronco-aseptilex, sulfadiazine, and other compounds of the commercial syrup. Enlargement of the salivary glands was observed after oral challenge tests with Bronco-aseptilex and sulfadiazine.

CONCLUSIONS:

We describe a patient who developed drug-induced sialadenitis. The oral challenge test confirmed that sulfadiazine was the etiologic agent.