bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Drug Reaction Reporting in a Multicenter Surveillance Study
Authors: Timm Edward G. , Welage Lynda S. , Walawander Cynthia A. , F.B. Sayers Jeffrey , Karpiuk Emilie L. , Davis Thomas D. , Grasela Thaddeus H.
Published: January 2017

Objective:

To evaluate the performance of a multicenter, prospective surveillance program in identifying adverse events, and to seek explanations for misclassification bias.

Design:

The design was a prospective observational study of patients with documented or suspected bacterial pneumonia.

Setting:

Data were collected in 74 acute care hospitals across the US.

Patients:

This evaluation was based on a consecutive sample of 1822 adult patients (>18 years of age) with documented or suspected bacterial pneumonia who were being treated with a cephalosporin, a penicillin, or an aminoglycoside over a 3-month period. Patients were followed for the duration of antibiotic therapy and were excluded if antibiotic therapy was <3 days or if the pneumonia was judged to be nonbacterial.

Interventions:

Clinical pharmacists documented patient demographics, concurrent illnesses and medications, antibiotic administration, relevant laboratory data, and the occurrence of nephrotoxicity and neutropenia.

Main Outcome Measures:

Validity of investigators’ identification of neutropenia and nephrotoxicity as compared with objective laboratory data was assessed by using sensitivity, specificity, and positive and negative predictive value measures.

Results:

Among the 1502 patients with sufficient data to evaluate neutropenia, there was agreement in 1270 patients (84.6%); likewise, among 129) patients with sufficient data to evaluate nephrotoxicity there was agreement in 1186 patients (91.9%). Sensitivity of the researchers’ assessments was 50.9% and 71.0% for neutropenia and nephrotoxicity, respectively. The negative predictive value was >95% for both events.

Conclusions:

Overall, this evaluation demonstrated that the Drug Surveillance Network can successfully identify targeted adverse events. Moreover, this study highlights the importance of validation for all types of outcomes-oriented research studies.
Emergency Department Resource use by Patients with Migraine and Asthma in a Health Maintenance Organization
Authors: Kaa Kathleen A. , Carlson James A. , Osterhaus Jane T.
Published: January 2017

Objective:

To identify and compare the resources consumed by patients with symptoms of asthma or migraine who presented to the Walk-In Emergency Department (WIED).

Design:

Chart review.

Setting:

WIED, Group Health Cooperative of Puget Sound, Seattle, WA.

Patients:

Identified via WIED records as having visited the WIED between October 1991 and February 1992 for migraine or asthma.

Main Outcome Measures:

Time spent in the WIED, medications administered during visit and prescribed at discharge, diagnostic procedures performed, referrals, and hospitalizations.

Results:

Of 16 755 WIED visits during the study period, 323 (1.9%) were migraine related and 159 (1.0%) were asthma related. Ninety percent of the asthma patients and 62% of the migraine patients reported having self-medicated prior to going to the WIED; 89% of the migraine patients received additional medication at the WIED versus 57% of the patients with asthma. Fifty-four (35.5%) of the migraine patients and 7 (4.6%) of the asthma patients had more than 1 WIED visit during the study period.

Conclusions:

Patients with asthma and migraine present striking contrasts in the types of resources used during WIED visits. This descriptive research highlights the need for further evaluation of the appropriateness of the healthcare services provided.
Piperacillin/Tazobactam: A New Beta-Lactam/Beta-Lactamase Inhibitor Combination
Authors: Schoonover Lori L , Occhipinti Donna J , Rodvold Keith A , Danziger Larry H
Published: January 2017

Objective:

To discuss the antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effect profile of piperacillin/tazobactam, a new beta-lactam/beta-lactamase inhibitor combination.

Data Sources:

Literature was identified by MEDLINE search of the medical literature, review of selected references, and data provided by the manufacturer.

Study Selection:

In vitro susceptibility data were surveyed from studies following the methods of the National Committee for Clinical Laboratory Standards. Data evaluating clinical efficacy were selected from all published trials and abstracts. Additional information concerning safety, chemistry, and pharmacokinetics was reviewed.

Data Synthesis:

The antimicrobial activity of piperacillin is enhanced by addition of tazobactam against gram-positive, gram-negative, and anaerobic bacteria. Tazobactam is active against a broad spectrum of plasmid and chromosomally mediated enzymes and has minimal ability to induce class I chromosomally mediated beta-lactamase enzymes. Piperacillin/tazobactam's expanded activity appears encouraging in the treatment of mixed aerobic and anaerobic infections. Direct comparisons of ticarcillin/clavulanate and piperacillin/tazobactam for the treatment of lower respiratory tract infections showed piperacillin/tazobactam to be clinically superior, and in the treatment of skin and soft tissue infections the 2 agents were comparable. For the treatment of intraabdominal infections, piperacillin/tazobactam was at least as effective as imipenem/cilastatin and clindamycin plus gentamicin.

Conclusions:

The combination of tazobactam with piperacillin results in an antimicrobial agent with enhanced activity against most beta-lactamase–producing organisms. Preliminary data indicate that piperacillin/tazobactam has proven clinical efficacy in the treatment of a variety of infections, especially polymicrobic infections.
Update on Tocolytic Therapy
Authors: McCombs Janet
Published: January 2017

Objective:

To review medications currently being used or investigated for the treatment of preterm labor. Adverse effects, pharmacoeconomic issues, and therapeutic controversies are included.

Data Sources:

A MEDLINE search, limited to English-language articles and publication years of 1989–1994, was used to identify pertinent literature. Additional references were identified from articles retrieved in the search.

Study Selection:

Studies were chosen on drugs that are available or whose approval is anticipated in the US: ritodrine, terbutaline, hexoprenaline, and magnesium sulfate. Several studies comparing indomethacin and nifedipine with currently used medications are also included. Oxytocin antagonists, now in Phase II clinical trials, are discussed. Studies focusing on adverse reactions were included because of serious concerns that these reactions raise.

Data Extraction:

Part of the controversy surrounding tocolytic agents involves the difficulty in comparing data from different trials, particularly because the criteria for diagnosis of preterm labor vary significantly. Therefore, no attempt was made to directly compare data from different sources; individual study data are presented.

Data Synthesis:

Most studies reviewed using the beta-agonists showed each to be comparable in effectiveness when given parenterally during early preterm labor. These drugs usually delay delivery for 24–48 hours. There is less evidence that they are consistently effective in the long-term treatment of preterm labor. The adverse effects vary somewhat, but all beta-agonists have been reported to cause pulmonary edema, which is the most serious adverse effect associated with the use of these medications to inhibit labor. Indomethacin and nifedipine may be alternative choices for tocolytic therapy, but each has different adverse reactions that also make them less than ideal agents. Oxytocin antagonists may provide more specific therapy and are currently being investigated.

Conclusions:

The beta-agonists are effective in delaying delivery for 24–48 hours in most patients; however, there are potential risks involved. Magnesium sulfate, prostaglandin synthetase inhibitors, calcium-channel blockers, and oxytocin antagonists may provide alternative choices for the treatment of preterm labor associated with neonatal morbidity and mortality. Each of the medications has advantages and disadvantages at different stages of gestation.
Rapid Infusion of Amphotericin B in Dextrose
Authors: Gales Mark A , Gales Barry J
Published: January 2017

Objective:

To review the data examining the use of rapid infusion of amphotericin B in dextrose infusions.

Data Sources:

A MEDLINE search of the English-language literature and review of pertinent references' bibliographies was used to identify articles evaluating the effect of amphotericin B infusion rates on the incidence of adverse reactions.

Study Selection and Data Extraction:

Controlled and uncontrolled studies involving humans are reviewed; emphasis is placed on recent comparative trials. Pertinent information, as judged by the authors, was selected for discussion.

Data Synthesis:

Amphotericin B, a polyene antifungal agent with significant toxicity, remains the agent of choice for many serious fungal infections. The potential benefits of rapid administration of amphotericin B in reducing the incidence and/or severity of adverse reactions were noted soon after its introduction. Recent studies have examined the tolerability of rapid (0.75–1 h) amphotericin B infusions. Results of studies assessing the tolerability of rapid amphotericin B infusions suggest that tolerance to infusion-related reactions develops during therapy. Comparative trials have obtained variable results. The comparative trials supporting rapid amphotericin B infusion have generally used crossover designs, enrolled small numbers of patients, and excluded patients with significant renal or cardiovascular dysfunction.

Conclusions:

Rapid amphotericin B infusions should be avoided during initiation of therapy when infusion-related reactions tend to be most problematic, and in patients with cardiovascular disease, renal dysfunction, and potassium disorders because of the potential risk for cardiac arrhythmias. The literature currently available is conflicting and insufficient to support the routine use of rapid amphotericin B infusion.
Quality Assessment of Economic Evaluations in Selected Pharmacy, Medical, and Health Economics Journals
Authors: Bradley Carole A , Iskedjian Michael , Lanctôt Krista L , Mittmann Nicole , Simone Carmine , Pierre Edith St , Miller Elizabeth , Blatman Brian , Chabursky Borys , Einarson Thomas R
Published: January 2017

Objective:

To assess and compare the quality of economic studies in selected pharmacy, medical, and health economics journals.

Data Sources:

DICP The Annals of Pharmacotherapy, American Journal of Hospital Pharmacy, Hospital Pharmacy, New England Journal of Medicine, Medical Care, Journal of the American Medical Association, PharmacoEconomics, International Journal of Technology Assessment in Health Care, and Journal of Health Economics using MEDLINE, EMBASE, and International Pharmaceutical Abstracts. Search terms included “economic,” “cost,” and “cost analysis.”

Study Selection:

Reviewers appraised abstracts to identify original research published during 1989-1993 comparing costs and outcomes between drugs, treatments, and/or services. Initially, 123 articles met criteria; 16 were inappropriate, 17 were randomized out, and 90 (73%) were used (30/group).

Data Extraction:

Quality was assessed using a 13-item checklist. Interrater reliability was 0.91 (p < 0.05) for 9 raters, test-retest reliability was 0.94 (p < 0.001).

Data Synthesis:

A 2-way ANOVA, with overall quality scores as a dependent variable with journal type and year as independent variables, was significant (F = 2.79, p = 0.002, r2 = 0.34), with no significant interaction (F = 0.71, p = 0.68) or time effect (F = 0.70, p = 0.60). Journal types differed; pharmacy journals scored significantly lower (χ2= 53.89, df = 2, p < 0.001). Items rated adequate (i.e., correct or acceptable) increased over time (χ2 = 21.18, df = 4, p < 0.001). Ethical issues and study perspective most needed improvement.

Conclusions:

Article quality for all journal types increased over time nonsignificantly; health economics journals scored highest, then medical journals, with pharmacy journals significantly lower (and having the highest standard deviation). We recommend that authors and reviewers pay closer attention to study perspective and ethical implications.
Use of Confidence Intervals and Sample Size Calculations in Health Economic Studies
Authors: Sacristán José A , Day Simon J , Navarro Olga , Ramos José , Hernández Jesûs M
Published: January 2017

Objective:

To discuss the calculation and application of confidence intervals in pharmacoeconomic studies.

Data Synthesis:

The increasing frequency with which pharmacoeconomic evaluations are made within clinical trials makes it possible to obtain information on the outputs and costs of an intervention in each patient of a sample under study. This allows the same statistical principles commonly used in clinical trials to be applied to cost or cost-effectiveness data. The methodology described in this article would allow expression of cost-effectiveness ratios in the form of confidence intervals. The calculation of the cost-effectiveness ratio by means of a confidence interval may have important practical consequences, both in decision-making on the choice of 1 intervention versus another and in calculating the size of the sample necessary to identify statistically significant differences, from both clinical and economic points of view.

Conclusions:

The complementary use of confidence intervals and sensitivity analysis makes it possible to measure uncertainty related and unrelated to variability in sample data, allowing the decision to adopt 1 technology or another to be based on the most objective information available. Although several ethical and methodologic concerns remain to be addressed, this methodology may contribute to improving the more rational and efficient use of drugs.
Octreotide Acetate in Refractory Bone Marrow Transplant-Associated Diarrhea
Authors: Crouch Michael A , Restino Maryann S , Cruz Julia M , Perry James J , Hurd David D
Published: January 2017

OBJECTIVE

To evaluate the effectiveness of octreotide acetate in the treatment of refractory bone marrow transplant—associated diarrhea.

DESIGN

Case series encompassing 30 months.

SETTING

A 12-bed bone marrow transplant unit at a tertiary care medical center.

PARTICIPANTS

Twenty-four patients with bone marrow transplant—associated diarrhea who did not improve with supportive or attapulgite therapy.

INTERVENTIONS

Patients received subcutaneous octreotide acetate at doses ranging from 50 to 250 μg 2 to 3 times daily. Concurrent treatment with antimotility or antisecretory agents did not occur.

MAIN OUTCOME MEASURES

The number of bowel movements and stool volumes were recorded daily. Complete response to octreotide therapy was defined as a reduction of both stool output and stool frequency by more than 50% within 72 hours. Partial response was defined as a reduction of either stool output or stool frequency by more than 50% within 72 hours. Treatment failure occurred if neither of the two parameters decreased by 50% within the designated time period.

RESULTS

Twenty-eight treatment challenges were initiated in the 24 patients evaluated. Diarrhea completely or partially subsided in 23 of 28 challenges (82.1%) within 72 hours. Stool output decreased from 1143 ± 595 at baseline to 252 ± 356 mL/d within 72 hours (p < 0.005). Stool frequency decreased from a baseline of 7.5 ± 3.4 to 2.7 ± 2.2 stools per day within 72 hours (p < 0.005). Adverse effects associated with octreotide were pain or burning at the injection site (24.1%), abdominal pain (13.8%), and increased stool output (6.9%).

CONCLUSIONS

These data suggest octreotide acetate significantly reduces stool output and frequency in patients with refractory bone marrow transplant—associated diarrhea. Additional research is necessary before this agent can be recommended for routine use in this patient population.
Evaluation of the Use of Cefuroxime and Cefuroxime Axetil in an Intravenous—Oral Stepdown Program
Authors: Malfair Suzanne C , Frighetto Luciana , Nickoloff Donna M , Martinusen Shelagh M , Jewesson Peter J
Published: January 2017

OBJECTIVE:

To characterize cefuroxime and cefuroxime axetil use under the influence of a parenteral-to-oral (iv—po) stepdown program.

DESIGN:

Open single-center retrospective review.

SETTING:

Tertiary care teaching and referral Canadian hospital with 1100 beds.

PATIENTS:

a random sample of 78 patients receiving cefuroxime was compared with a random sample of 50 patients receiving iv—po cefuroxime stepdown.

RESULTS:

During the first 6 months following formulary introduction, 1535 patients received cefuroxime. Stepdown to any oral antibiotic occurred in 22% of patients. Cefuroxime axetil was used as the stepdown agent in 64% of these cases. In a comparison of nonstepdown courses with stepdown courses, some differences were apparent. Nonstepdown treatment courses were primarily prophylactic, whereas stepdown courses were typically initiated as primary therapy for the 10-day management of respiratory tract infections (p < 0.001). Conversion to oral therapy typically occurred on day 5 of parenteral therapy and continued for 5 days. Stepdown was considered possible in 46% of treatment courses in which this process did not happen. When stepdown did occur, it was considered timely in 64% of cases, unnecessarily delayed in 32%, and premature in 4% of treatment courses. Stepdown did not appear to be associated with a negative impact on patient outcome. Mean ± SD cost of drug therapy per day was less for the stepdown group (US $15.78 ± $5.97) than the nonstepdown group (US $25.47 ± $7.87; p < 0.001).

CONCLUSIONS:

As a result of this study we intend to maintain cefuroxime and cefuroxime axetil on the formulary and continue to judiciously promote the timely conversion to oral therapy.
Lorazepam Stability in Parenteral Solutions for Continuous Intravenous Administration
Authors: Hoey Lori L , Vance-Bryan Kyle , Clarens Diann M , Wright David H , Konstantinides Frank N , Guay David RP
Published: January 2017

OBJECTIVE:

To determine the stability of lorazepam over a 24-hour period when prepared in polyvinyl chloride (PVC) bags at initial concentrations of 0.08 and 0.5 mg/mL.

DESIGN:

Each concentration was studied at room (21°C) and refrigerator (4°C) temperatures in dextrose 5% (D5W) and NaCl 0.9% solutions. Duplicate test solution admixtures were prepared for each lorazepam concentration, diluent, and temperature. At 0, 1, 4, 8, and 24 hours, duplicate samples were obtained for visual inspection, pH determination, and concentration determination by stability-indicating, reverse-phase HPLC analysis. Compared with baseline, peaks for lorazepam degradation products were not found on any of the study chromatograms.

RESULTS:

In D5W and NaCl 0.9% solutions, lorazepam loss in excess of 10% by HPLC analysis occurred for concentrations of 0.08 and 0.5 mg/mL at 1 and 4 hours, respectively.

CONCLUSIONS:

These data suggest that significant loss of lorazepam occurs as the probable result of sorption to PVC bags when admixed in both D5W and NaCl 0.9% solutions at 21 and 4°C.
Effects of Ofloxacin Administration on the Reliability of Urine Glucose Testing
Authors: Tsai Tsong-Mei , Shea Brian F , Souney Paul F , Volinsky Fred G , Scavone Joseph M , O'Neill Suellen
Published: January 2017

OBJECTIVE:

TO study the effects of ofloxacin on the reliability of urine glucose testing.

DESIGN:

Open-label, nonrandomized.

SETTING:

A university-affiliated tertiary care hospital, ambulatory clinic.

PARTICIPANTS:

Ten healthy volunteers (8 men and 2 women) aged 22-39 years.

MAIN OUTCOME MEASURES:

Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0–4 hours postdose, and (3) pooled 4–8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing.

RESULTS:

None of the ofloxacin concentrations in phase I (0,25,50, 100, 200,400, and 800 μg/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II.

CONCLUSIONS:

In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations. Supported by a grant from the RW Johnson Pharmaceutical Research Institute. Presented in abstract form at the American College of Clinical Pharmacy 1994 Winter Practice and Research Forum, February 6–9, 1994, San Diego. CA.
Pharmacokinetics and Pharmacodynamics of Glyburide in Young and Elderly Patients with Non-Insulin-Dependent Diabetes Mellitus
Authors: Jaber Linda A , Antal Edward J , Welshman Ian R
Published: January 2017

OBJECTIVE:

TO determine the influence of age on the pharmacokinetics and pharmacodynamics of glyburide after acute and chronic dosing in young and elderly subjects with non-insulin-dependent diabetes mellitus.

DESIGN:

Ten elderly (mean age 69.3 ± 3.1 y) and 10 younger (mean age 45.6 ± 4.5 y) patients received a glucose challenge test at baseline, with a 2.5-mg dose of glyburide at week 0 (acute dose) and again at weeks 6 and 12 of chronic glyburide therapy. Glyburide doses were titrated to a maximum daily dosage of 20 mg to achieve a glucose concentration of 7.8 mmol/L or less. During 24-h pharmacokinetic determinations at weeks 0, 6, and 12, serial blood samples were obtained for glyburide determination with HPLC. Serial blood samples for glucose, insulin, and C-peptide determinations were obtained at baseline (week −1) and at weeks 0, 6, and 12.

RESULTS:

All pharmacokinetic parameters assessed for glyburide were statistically comparable between the two age groups with the exception of a shorter time to peak concentration in the elderly at weeks 0 and 12. The glucose pharmacodynamic response to glyburide was not statistically different between the two groups. However, there was a statistically significant greater C-peptide response in the elderly group at all evaluation weeks.

CONCLUSIONS:

Aging appears to have no influence on the pharmacokinetics of glyburide. Observed pharmacodynamic differences indicate the necessity for dosage titration to a specified therapeutic response regardless of patient age.
Enoxaparin for Unstable Angina and Ancrod for Cardiac Surgery following Heparin Allergy
Authors: Smith Reginald E , Townsend Gary E , Berry Brian R , Bowen Tom
Published: January 2017

OBJECTIVE:

To describe a patient who presented with heparin allergy and required alternate anticoagulation for unstable angina and coronary artery bypass surgery. To review therapeutic alternatives to porcine heparin for patients with hypersensitivity or intolerance to standard heparin anticoagulation.

CASE SUMMARY:

A 74-year-old man with a 15-year-old coronary artery bypass graft presented to the emergency room with unstable angina and was scheduled for urgent coronary artery revascularization. A bolus dose of porcine heparin was administered followed by a continuous infusion. Shortly afterward the patient developed a type I allergic reaction to the porcine heparin that was confirmed by rechallenge. Three alternatives to porcine heparin were tried, including bovine lung heparin, low-molecular-weight heparin (enoxaparin), and ancrod. The patient was found to be cross-sensitive to bovine lung heparin, but tolerated enoxaparin for unstable angina without cross-sensitivity. Anticoagulation for cardiopulmonary bypass was achieved with an infusion of ancrod that was later reversed with cryoprecipitate. The patient was discharged postoperatively on day 5 without the complication of excessive bleeding.

DISCUSSION:

Type I allergic reaction to unfractionated heparin is a rare occurrence and could be the result of a variety of factors. Possible causes for the reaction include a porcine protein, a preservative contained in the heparin solution, or a hapten formed between heparin and a plasma protein. We considered four alternatives to heparin anticoagulation: rush desensitization, bovine lung heparin, low-molecular-weight heparin, and ancrod. The patient was cross-sensitive to bovine lung heparin, but was able to tolerate low-molecular-weight heparin (enoxaparin). This was unexpected because enoxaparin is derived from unfractionated porcine heparin. Testing for cross-sensitivity had no value in this case, as two negative subcutaneous test doses were followed by dramatic reactions when the drugs were given intravenously. Although enoxaparin has been used for anticoagulation during bypass surgery, there is more experience with ancrod as an alternative to heparin. Repeat bypass surgery, which normally results in above-average blood loss, was successfully performed with a very low fibrinogen concentration (<0.15 g/L) during ancrod anticoagulation.

CONCLUSIONS:

We conclude that ancrod was a safe and effective alternative to heparin for coronary artery bypass surgery in this patient in whom a heparin product had caused a hypersensitivity reaction. We discovered on two occasions that a negative subcutaneous test dose for heparin allergy did not predict a severe type I allergic reaction when the heparin was later administered intravenously. Furthermore, we found that a low-molecular-weight heparin administered subcutaneously for a short period of time did not cause cross-sensitivity in a patient with a type I allergy to unfractionated heparin.
Quinine Clearance in Continuous Venovenous Hemofiltration
Authors: Davies J Graham , Greenwood Elizabeth F , Kingswood J Christopher , Sharpstone Paul , Street Martin K
Published: January 2017

OBJECTIVE:

TO describe a case involving the removal of quinine by continuous venovenous hemofiltration (CVVH) in a patient with malaria and acute renal failure and to present recommendations on the dosing of quinine in such patients.

CASE SUMMARY:

A 50-year-old white man developed Plasmodium falciparum malaria following a visit to Nigeria. Although he received intravenous quinine, his condition deteriorated and he required intensive care management, including CWH for the management of his acute renal failure. Quinine plasma concentrations were measured to determine both total body and extracorporeal clearance of the drug.

DISCUSSION:

TO our knowledge this is the first report quantifying the removal of quinine by CVVH. The drug is not significantly removed by this extracorporeal process. The filter clearance accounted for less than 1.5% of the total body clearance.

CONCLUSIONS:

Initially the dosage of quinine administered to patients presenting with P. falciparum infection should not be reduced because of renal failure. This is particularly important when cerebral involvement is suspected. Subsequent dosage modification should reflect the severity of the patient's clinical condition and the plasma quinine concentration achieved, and should not be limited by the degree of renal impairment present.
Acetazolamide in the Treatment of Seizures
Authors: Reiss William G , Oles Karen S
Published: January 2017

OBJECTIVE:

TO summarize the pharmacology, pharmacokinetics, efficacy, and safety of acetazolamide and to evaluate its therapeutic role in patients with epilepsy.

DATA SOURCES:

A computerized search of the MEDLINE (OVID) database (1966–1994) was used to identify publications regarding acetazolamide. The MEDLINE search was supplemented by information from textbooks.

STUDY SELECTION:

Included were English-language review articles, clinical trials, cohort studies, and case reports. Topics investigated included basic pharmacology, therapeutics, toxicology, adverse reactions, dosage, administration, and pharmacokinetics of acetazolamide.

DATA SYNTHESIS:

Acetazolamide, a carbonic anhydrase inhibitor, has been approved for the treatment of epilepsy since 1953. Acetazolamide is primarily used in combination therapy with other antiepileptic medications in both children and adults although it may be used as monotherapy. Drug concentration monitoring has not been found to be routinely beneficial. Adverse effects include kidney stones, metabolic acidosis, lethargy, appetite suppression, paresthesias, and rare blood dyscrasias. Partial tolerance may develop to the antiepileptic activity.

CONCLUSIONS:

Acetazolamide is a beneficial adjunctive agent in the pharmacotherapy of epilepsy and should be considered in refractory epilepsy. Although it may be useful in partial, myoclonic, absence, and primary generalized tonic—clonic seizures uncontrolled by other marketed agents, acetazolamide has been inadequately studied by current standards and its use has been limited.
Possible Interaction Involving Phenytoin, Dexamethasone, and Antineoplastic Agents: A Case Report and Review
Authors: Gattis Wendy A , May D Byron
Published: January 2017

OBJECTIVE:

TO describe a patient with subtherapeutic phenytoin concentrations and to review the literature regarding a possible interaction between phenytoin and chemotherapeutic agents as well as dexamethasone.

CASE SUMMARY:

A 29-year-old white man with brain metastases secondary to malignant melanoma consistently had suboptimal phenytoin concentrations while receiving chemotherapy consisting of cisplatin, carmustine, dacarbazine, and tamoxifen. In addition, this patient received dexamethasone, which may have influenced his phenytoin concentrations.

DATA SOURCES AND STUDY SELECTION:

Case reports were identified through a MEDLINE search and by cross referencing the articles identified.

DISCUSSION:

The available literature addressing suboptimal phenytoin concentrations in the setting of chemotherapy is reviewed. Aggressive dosing of phenytoin may be required to achieve therapeutic concentrations in patients who are concurrently receiving chemotherapy and/or dexamethasone, especially in patients who fall outside the predictive pharmacokinetic model for phenytoin.

CONCLUSIONS:

Subtherapeutic phenytoin concentrations may be decreased secondary to several proposed mechanisms: (1) the patient falls outside the predicted pharmacokinetic population parameters for phenytoin, (2) phenytoin absorption is decreased secondary to chemotherapy-induced gastrointestinal toxicity, and (3) metabolism of phenytoin is increased secondary to chemotherapy agents.
Pathophysiology and Management of the Serotonin Syndrome
Authors: Brown Thomas M , Skop Brian P , Mareth Thomas R
Published: January 2017

OBJECTIVE:

TO review the symptoms, pathophysiology, and treatment of the serotonin syndrome (SS).

DATA SOURCES:

A MEDLINE search (1957–1995) of the English-language literature pertaining to the SS was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search.

STUDY SELECTION AND DATA EXTRACTION:

All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion.

DATA SYNTHESIS:

The SS, an occasionally fatal disorder, is characterized by symptoms such as mental status changes, seizures, myoclonus, and blood dyscrasias. Both the central and peripheral serotonergic systems and several serotonin receptor types are involved in the symptomatology of the SS. The pathogenesis of SS may be due to endogenous as well as iatrogenic deficits in peripheral serotonin metabolism, a stimulus for release of serotonin, and interactions with other neurotransmitter systems. Lorazepam, serotonin-blockers, and nitroglycerin have been used successfully to treat SS.

CONCLUSIONS:

The SS is increasingly recognized and reported in the literature. Clinical and basic science research have increased our understanding of the pathophysiology, conditions, and agents that may predispose to the development of the syndrome. Newer treatment strategies are discussed.
Site-Specific Pharmacokinetics and Pharmacodynamics of Intramuscular Meperidine in Elderly Postoperative Patients
Authors: Erstad Brian L , Meeks Mimi L , Chow Hsiao-Hui , Rappaport William D , Levinson Miriam L
Published: January 2017

OBJECTIVE:

To examine and compare the pharmacokinetics and pharmacodynamics of meperidine when administered intramuscularly at gluteal and deltoid sites in elderly postoperative patients.

DESIGN:

Prospective, randomized investigation.

SETTING:

Tertiary care university teaching hospital.

PATIENTS:

Fourteen patients 60 years of age or older who were undergoing general surgery.

INTERVENTION:

A single dose of meperidine 0.75 mg/kg given intramuscularly at either a deltoid or gluteal site.

MAIN OUTCOME MEASURES:

Pharmacokinetic (based on concentration—time curves) and pharmacodynamic (i.e., pain scales, need for additional pain medication) comparisons were made, based on site of meperidine injection.

RESULTS:

No statistically significant differences were found in the maximum plasma concentration, volume of distribution, or clearance of meperidine by site of injection. Substantial interpatient variability in pharmacokinetic parameters was noted for both sites (range of maximum concentrations: 191–500 ng/mL gluteal, 166–374 ng/mL deltoid). Although pain scores were similar for the two groups, four of the patients in the group given gluteal injection required additional breakthrough pain management within 4 hours of meperidine injection compared with one patient in the group given deltoid injection.

CONCLUSIONS:

There is no obvious relationship between meperidine pharmacokinetic and pharmacodynamic parameters, regardless of intramuscular injection site. Breakthrough pain is common when patients are given intramuscular injections postoperatively, particularly when the gluteal route is used. When meperidine is used for analgesia in elderly postoperative patients, consideration should be given to more rapid and predictable routes (e.g., intravenous injection) of meperidine administration.
Evaluation of Drug Interaction Document Citation in Nine On-Line Bibliographic Databases
Authors: Barillot Marine J , Sarrut Bernard , Doreau Christian G
Published: January 2017

OBJECTTVE:

To compare nine on-line bibliographic databases to obtain bibliographic references on specific drug interactions.

DESIGN:

Seven bibliographic databases were selected for their ability to provide information concerning drug interactions: EMBASE, MEDLINE, TOXLINE, BIOSIS, Chemical Abstracts (CAS), PHARMLINE, and International Pharmaceutical Abstracts (IPA). Two French on-line bibliographic databases (i.e., PASCAL, BIBLIOGRAPHIF) were also tested to compare them with the other international databases. Twenty drug interactions were selected randomly using the journal Reactions Weekly 1993.

MAIN OUTCOMES MEASURES:

The total number of references, the number of potentially relevant references, the number of case report references, the number of unique references in the total number of references, and the number of unique references between potentially relevant references were analyzed by using the Friedman two-way ANOVA by ranks. For each database, relevance and relative recall were calculated.

RESULTS:

For the total number of references, EMBASE was significantly more comprehensive than all other databases (p < 0.05). EMBASE had a significantly greater number of potentially relevant references than IPA, PHARMLINE, CAS, and BIBLIOGRAPHIF (p < 0.05). For the total number of case report references, only one significant difference, between EMBASE and BIBLIOGRAPHIF (p < 0.05), was observed. MEDLINE and TOXLINE had the lowest cost per potentially relevant reference.

CONCLUSIONS:

To obtain bibliographic references on drug interactions, the first step should be to search MEDLINE or TOXLINE; the second step, for completeness, should be to search EMBASE.
Metformin-Associated Nonketotic Metabolic Acidosis
Authors: Jurovich Mark R , Wooldridge John D , Force Rex W
Published: January 2017

OBJECTIVE:

To document a case of anion gap, nonketotic metabolic acidosis occurring in a patient with acute renal failure who was receiving metformin.

CASE SUMMARY:

A 67-year-old white man presented with a 9-day history of weakness, nausea, dizziness, and difficulty moving; he had also not eaten during the previous 2 days. The patient had numerous abnormalities on his serum chemistry panel and arterial blood gases, including a pH of 7.1 and an anion gap of 21 mEq/L. No ketones were detected in the urine. The patient was treated with intravenous fluids, sodium bicarbonate, insulin, and hemodialysis. All medications were discontinued. The acidosis resolved shortly after hemodialysis. The hospital course was complicated by the onset of atrial fibrillation occurring on day 2 that did not respond to chemical cardioversion. On day 6 the patient was discharged home with resolving acute renal failure and normal serum pH.

CONCLUSIONS:

The mortality rate of biguanide-induced lactic acidosis is approximately 50%; thus, early recognition and treatment are essential. Suspicion of lactic acidosis should be high when diabetic patients who are taking a biguanide present with acidosis. The majority of cases of metformin-induced lactic acidosis have occurred in patients with contraindications to the drug (i.e., renal dysfunction). Thus, it is important to maintain strict adherence to these contraindications and monitor patients for deteriorating renal function.
Nilutamide: An Antiandrogen for the Treatment of Prostate Cancer
Authors: Dole Ernest J , Holdsworth Mark T
Published: January 2017

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of nilutamide and to compare this agent with the currently marketed nonsteroidal antiandrogens (i.e., bicalutamide, flutamide) by critically analyzing the published literature.

DATA SOURCES:

MEDLINE (1980–1995) and CANCERLIT (1991–1995) were searched for English-language publications using the terms nilutamide, bicalutamide, and flutamide alone, and either nilutamide or androgen antagonists in combination with prostatic neoplasms.

STUDY SELECTION AND DATA EXTRACTION:

All articles with subject matter on nilutamide, bicalutamide, and flutamide were considered for inclusion. For studies published in more than one journal, the first publication was used unless a subsequent publication included additional or follow-up data, in which case the latter publication was cited instead.

DATA SYNTHESIS:

Nilutamide was effective in combination with orchiectomy in improving responses in patients with advanced prostate cancer. However, patient survival was not improved in these trials, and improvements in bone pain did not usually result in improved performance status in these patients. The few trials of nilutamide monotherapy or nilutamide in combination with a luteinizing hormone-releasing hormone analog are too small to draw meaningful conclusions regarding its efficacy or its role in the treatment of advanced prostate cancer. No comparative trials of nilutamide with other antiandrogens and no analysis of the impact of nilutamide on patient quality of life are currently available. Nilutamide appears to produce a higher frequency of adverse effects than the other currently marketed nonsteroidal antiandrogens, bicalutamide and flutamide.

CONCLUSIONS:

Nilutamide does not appear to represent a major advance in the treatment of advanced prostate cancer and appears to be somewhat inferior to both flutamide and bicalutamide with regard to adverse effects. Nilutamide should not be considered the antiandrogen of choice in the treatment of advanced prostate cancer.
“Isolated” Low High-Density Lipoprotein Cholesterol
Authors: Wilt Vickie M , Gums John G
Published: January 2017

OBJECTIVE:

To present information on the function, structure, and importance of high-density lipoprotein cholesterol (HDL-C) and to evaluate the current literature regarding the controversy of managing patients with an “isolated” low HDL-C concentration.

DATA SOURCE:

A MEDLINE search was performed (1966–June 1996) to identify English-language clinical and review articles pertaining to HDL-C. Some articles were identified through the bibliography of selected articles.

STUDY SELECTION:

All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion.

DATA EXTRACTION:

Important historical lipid studies, recent review articles, and clinical trials involving therapy for HDL-C were evaluated.

DATA SYNTHESIS:

The structure, function, and measurement of HDL-C and the state of an isolated low HDL-C are discussed for background. Lifestyle modification measures to increase HDL-C, medications to avoid, estrogen replacement, and lipid-altering agents used to raise an isolated low HDL-C are presented.

CONCLUSIONS:

An isolated low HDL-C concentration poses a risk for coronary heart disease. The management of this state is controversial. The first step in management is in agreement with experts and includes lifestyle modification (e.g., weight reduction, diet, smoking cessation, aerobic exercise). Estrogen replacement therapy and discontinuance of drugs that secondarily lower HDL-C are additional treatment options. The use of lipid-altering agents has been used in some patients. Nicotinic acid appears to be an effective agent for an isolated low HDL-C. A large clinical trial evaluating the effect of treating an isolated low HDL-C for primary and secondary prevention of coronary events is needed.
Achilles Tendon Rupture Repair: Biomechanical Comparison of the Triple Bundle Technique versus the Krakow Locking Loop Technique
Authors: Jaakkola Juha I. , Hutton William C. , Beskin James L. , Lee Gregory P.
Published: January 2017

This study was designed to compare the tensile strength of ruptured Achilles tendons repaired using either the triple bundle technique or the Krakow locking loop technique. Eight pairs of fresh frozen cadaveric Achilles tendons were harvested. A simulated “Achilles tendon rupture” was created 4 cm from the calcaneal insertion in all sixteen tendons by transversely cutting the tendon with a scalpel. One Achilles tendon “rupture” of a pair was repaired using the triple bundle technique, while the other tendon of the pair was repaired using the Krakow locking loop technique. Then, using a servohydraulic testing machine, each tendon was tested to failure in tension at a displacement rate of 2.54 cm/sec. The average rupture load for the triple bundle technique was 453 N (range 397 ñ 549 N), while the average rupture load for the Krakow locking loop technique was 161 N (range 121 ñ 216 N). This difference in averages represents a statistically significant superiority of 2.8 to 1 (p < 0.001) in favor of the triple bundle technique.
Psychogenic Equinovarus: The Importance of Recognition and Non-operative Treatment.
Authors: Michelson James D.
Published: January 2017

Although the potential for musculoskeletal symptoms in hysteric conversion disorder was recognized by Sigmund Freud, reports of it in the orthopaedic literature have been limited to upper extremity manifestations. This study reports 3 cases which illustrate hysteric conversion presenting as primary foot and ankle complaints. Given its relative rarity, it is a diagnosis that is easy to miss. Clinical clues to its diagnosis and accepted methods of treatment are discussed. It is important to realize that this condition arises from an unconscious conflict and does not represent a voluntary falsification of symptoms. As such, confrontational treatment is not generally successful.
Popliteal Fossa Neural Blockade as the Sole Anesthetic Technique for Outpatient Foot and Ankle Surgery
Authors: Hansen Eric , Eshelman Martha R. , Cracchiolo Andrea
Published: January 2017

Foot and ankle operations are being performed with greater frequency as outpatient procedures. Although the surgical procedure remains the same whether the operation is done in an inpatient or an oupatient setting, the anesthesia and postoperative analgesia are greatly affected when patients must be discharged soon after their operation. We have evaluated a regional anesthetic technique which blocks the sciatic nerve in the popliteal fossa and the saphenous nerve block at the knee. This was the sole anesthetic technique for both the operation and the immediate postoperative period. This technique appears to have several advantages: 1) Excellent anesthesia during the operation and for about ten hours postoperatively; 2) Use of a proximal calf tourniquet, and 3) Absence of systemic or local complications as might be seen with general, spinal or epidural anesthesia.
Progressive Pedal Macrodactyly Surgical History with 15 year Follow-up
Authors: Sobel Ellen , Giorgini Renato J. , Potter Gene K. , Schwartz Robert D. , Chieco Tina M.
Published: January 2017

Macrodactyly can affect the fingers and/or toes1. Histopathologic examination will distinguish macrodactylia fibrolipomatosis or neural fibrolipoma with macrodactyly, from macrodactylia as a part of neurofibromatosis. Surgical repair is aimed at decreasing the size of the affected foot so it is as near in size and shape to the normal foot as possible. Surgical approaches have included reconstructive surgery (usually staged debulking procedures), epiphyseal plate arrest and amputation. Repeated reconstructive surgical procedures, as illustrated in this report covering patient care over a 15 year period, are usually necessary due to recurring soft tissue and boney enlargement.
Containment bag for jet lavage irrigation of the foot and ankle
Authors: Trepman Elly , Denham Joy
Published: January 2017

A clear plastic surgical bag which has an incorporated closure string may be used to contain fluid during jet lavage irrigation of foot and ankle wounds. This method may prevent fluid from spraying about, improving barrier precautions for both patient and operating room personnel.
Immobilization With Removable Walking Brace for Treatment of Chronic Foot and Ankle Pain
Authors: Crincoli Michael G. , Trepman Elly
Published: January 2017

Fifty feet and ankles in 47 patients (three bilateral) (26 women and 21 men; average age, 44 ± 15 years) were treated for chronic foot and ankle pain (duration: minimum, three months; average, 27 ± 35 months; range, three to 132 months). Evaluation included detailed history, physical examination, and radiography. Initial treatment consisted of immobilization (full weight-bearing) using a removable walking brace (23.5 hours per day, including in bed at night), with standing and walking limited to activities of daily living. Follow-up evaluation included assessment of pain response and repeat physical examination. There was a history of trauma in 32 (64%) feet and ankles. Braces (pneumatic in 31 [62%] and double-upright in 19 [38%] feet and ankles) immobilized the ankle in neutral position and included a rigid rocker sole. After an average of 13 ± 10 weeks (range, three to 50 weeks) of brace use, pain symptoms were improved in 35 (70%), unchanged in 11 (22%), and worse in four (8%) feet and ankles. Physical examination was improved in 43 (86%) feet and ankles, unchanged in six (12%) feet and ankles, and worse in one (2%) foot and ankle. In all 50 feet and ankles, the average number of abnormal physical findings decreased from initial (6 ± 3 abnormal physical findings) to follow-up evaluation (3 ± 3 abnormal physical findings) (P < 0.001). The average number of diagnoses per foot and ankle decreased from initial (4 ± 1 diagnoses per foot and ankle) to follow-up evaluation (2 ± 1 diagnoses per foot and ankle) (P < 0.0001). Improvement of pain was independent of duration of pre-existing symptoms, patient age, gender, or type of brace used. In summary, immobilization with a removable walking brace may improve chronic foot and ankle pain and localize the primary source of symptoms.