bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosing Adjustment of 10 Antimicrobials for Patients with Renal Impairment
Authors: Preston Sandra L , Briceland Laurie L , Lomaestro Ben M , Lesar Timothy S , Bailie George R , Drusano George L
Published: January 2017

Objective:

To describe a program of creatinine clearance–based dosage adjustment of 10 renally eliminated antimicrobial agents and to discuss the utility of such a program in a hospital as a method of quality assurance (by ensuring that patients with renal impairment receive generally accepted dosage adjustments), based on pharmacodynamic principles.

Methods:

Consecutive patients prescribed any of 10 targeted renally eliminated antibiotics were included. Recommendations for dosage adjustment were made to the prescriber based on a calculated creatinine clearance. Additional adjustments in drug therapy were performed, including dosage recommendations of nontargeted drugs, simplification of antibiotic regimens, and conversion of intravenous to oral therapy. A cost analysis was performed.

Results:

During a 6-month study period, 160 dosage changes (7.6% of total number screened) were recommended in 137 patients receiving the targeted antimicrobial agents. Prescribers accepted 147 recommendations (91.9%). A dosage change recommendation was necessary more than 12% of the time for acyclovir, ceftazidime, and imipenem/cilastatin. A cost avoidance of $11 702.08 was realized. Ancillary drug recommendations that were offered and accepted during the program realized a cost avoidance of $6613.75.

Conclusions:

This dosage adjustment program using pharmacodynamic principles was successful in optimization of dosing, potential minimization of morbidity caused by excessive dosing, and demonstration of direct and potentially indirect cost avoidance. A dosing program for patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.
Experience in The Development of a Postmarketing Surveillance Network: The Pharmacy Medication Monitoring Program
Authors: Willison Donald J , Gaebel Kathryn A , Borden E Keith , Levine Mitchell Ah , Poston Jeffrey W , Goldsmith Charles H , Wong Bruce
Published: January 2017

Objective:

To describe the pilot and early implementation phase of a system for assembling and recruiting cohorts of patients taking selected prescription medications and prospectively monitoring them for new health events.

Design:

Prospective observational study, based on telephone interviews, of 1475 patients filling prescriptions for a nonsteroidal antiinflammatory drug (NSAID). Patients were interviewed by telephone using trained interviewers at a central site. Hospitalizations and deaths were followed up and reviewed by an independent physician.

Setting:

Community setting in a region of Hamilton, Ontario, Canada.

Participants:

All consenting patients filling new or repeat prescriptions for NSAIDs at participating pharmacies.

Main Outcome Measures:

The authors report on the development and assessment of systems for: (1) ongoing recruitment of patients through community pharmacies; (2) data transfer from pharmacies to the coordinating center; (3) surveying patients; (4) classifying, coding, and evaluating new health events; and (5) following up on new serious adverse events.

Results:

Fifty-one percent of patients approached were recruited, and 83% of these provided completed interviews. For patients picking up their own medications, pharmacy workload varied from 4 to 10 minutes per patient approached. Nineteen percent of patients reported having a new health problem or unusual symptom at the initial telephone interview. Reported health-related events were similar to those described in other studies of NSAIDs.

Conclusions:

Most aspects of the monitoring system performed well. One limitation was the low recruitment rate for patients who did not directly drop off or pick up their own prescriptions. Even so, this method of patient accrual may complement alternative monitoring programs.
Glutathione in Health and Disease: Pharmacotherapeutic Issues
Authors: Lomaestro Ben M , Malone Margaret
Published: January 2017

Objective:

To review the current research and importance of glutathione (GSH) therapy in health and disease and to provide a basic overview of the widespread use and interest in this compound.

Data Identification:

Articles were obtained via a MEDLINE search of the term glutathione in conjunction with specific disease states mentioned, and via extensive review of references found in articles identified by computer search.

Study Selection:

Emphasis was placed on the most recent research, human research, and in discussing multiple disease states.

Data Extraction:

The literature was reviewed for methodology, quality, and practical aspects of interest to clinical pharmacists.

Data Synthesis:

GSH is a tripeptide of extreme importance as a catalyst, reductant, and reactant. It continues to be investigated in diverse areas such as acute respiratory distress syndrome, toxicology, AIDS, aging, oncology, and liver disease. Despite the widespread clinical interest in GSH, we were not able to identify an in-depth review of this compound in the pharmacy literature.

Conclusions:

The list of potential indications for modulation of GSH is extensive and broad. This review introduces clinicians to what GSH is, its basic chemistry, and some areas of active research.
Effects of Aspirin and Ibuprofen on the Pharmacokinetics and Pharmacodynamics of Glyburide in Healthy Subjects
Authors: Kubacka Renée T , Antal Edward J , Juhl Randy P , Welshman Ian R
Published: January 2017

OBJECTIVE:

To determine the effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy volunteers.

DESIGN:

Single-center, randomized, two-way, crossover design following an initial baseline evaluation phase.

SETTING:

Outpatient, university-based ambulatory care facility.

PATIENTS:

Sixteen healthy nonsmoking men aged 20–34 years.

INTERVENTION:

Three phases consisting of six treatments. Phase 1 began with treatment A, a baseline oral glucose tolerance test (GTT), followed by treatment B, glyburide 5 mg plus a GTT. The other two phases were administered in a crossover design. Phase 2 consisted of the administration of aspirin 975 mg qid for 4 days. On day 3 a GTT was administered (treatment C) and on day 4 glyburide 5 mg plus a GTT was administered (treatment E). Phase 3 consisted of the administration of ibuprofen 600 mg qid for 4 days with a GTT on day 3 (treatment D) and glyburide 5 mg plus a GTT on day 4 (treatment F).

MAIN OUTCOME MEASURES:

Serum glyburide concentrations after each treatment, as well as glucose and insulin, ibuprofen, and salicylate serum concentrations and glyburide free fractions.

RESULTS:

Aspirin administration resulted in an 85% increase in mean total glyburide oral clearance and a 29% increase in glyburide free fraction. Ibuprofen administration resulted in a slight increase in mean glyburide free fraction, but no significant changes in glyburide pharmacokinetic parameters were observed. Insulin concentrations were increased during the glyburide plus aspirin treatment. Conflicting results were observed in the glucose parameters.

CONCLUSIONS:

The potential for this glyburide—aspirin interaction resulting in a transient hypoglycemia should be considered in diabetic patients receiving glyburide therapy.
Survey of Antibiotic Control Policies in University-Affiliated Teaching Institutions
Authors: Lesar Timothy S , Briceland Laurie L
Published: January 2017

OBJECTIVE:

To determine the type and extent of antibiotic control policies currently in use in a group of university-affiliated teaching institutions.

DESIGN:

A survey of antibiotic control policies and procedures (e.g., antibiotic order sheets, formulary restrictions, automatic stop orders for specific indications) was developed.

SETTING:

The University Hospital Consortium (UHC), a nonprofit group of academic health centers located in 33 states throughout the US.

PARTICIPANTS:

The survey was mailed to 60 UHC members.

RESULTS:

The survey was returned by 48 (80%) institutions. Most hospitals use either restrictions (81%) and/or official recommendations (56%) to manage antibiotic use. Antibiotics were restricted most commonly by service or unit (69%), indication (69%), or to the infectious disease service (60%). Antibiotic order sheets are used in 21 (44%) of the hospitals, of which 14 require completion by the prescriber. Monitoring of compliance with established restrictions is primarily the responsibility of the pharmacist processing the order (84%) and/or a clinical pharmacist (53%). When an order does not comply with restrictions or compliance cannot be determined, the prescriber is contacted prior to dispensing in 77% and 83% of the cases, respectively. In cases of noncompliance in which the prescriber refuses to alter an order to meet restrictions, 40% of hospitals refuse to dispense the drug and 35% dispense the drug but refer the case to another authority (infectious disease service or pharmacy and therapeutics committee).

CONCLUSIONS:

Considering the widespread use of antibiotic control programs, further investigation of the success of such programs in optimizing drug therapy, improving patient outcome, and curtailing the antibiotic budget within and among specific institutions is warranted.
Severe Rhinorrhea and Respiratory Distress in a Neonate Exposed to Fluphenazine Hydrochloride Prenatally
Authors: Nath Shanta P , Miller Debra A , Muraskas Jonathan K
Published: January 2017

OBJECTIVE:

To report a case of respiratory distress with severe rhinorrhea in a newborn exposed prenatally to fluphenazine hydrochloride.

CASE SUMMARY:

The safety of phenothiazines during pregnancy and the effect on the fetus and newborn are not well known. We describe a newborn who had severe rhinorrhea, vomiting, and respiratory distress after being exposed in utero to fluphenazine hydrochloride. Sepsis, choanal atresia, and congenital syphilis were excluded as causative factors for rhinorrhea. The rhinorrhea and upper airway obstruction responded to treatment with pseudoephedrine.

CONCLUSIONS:

Severe rhinorrhea, vomiting, and respiratory distress that occurred in this infant have not been reported previously following prenatal fluphenazine hydrochloride exposure. Awareness of this problem would be helpful to clinicians and should be considered in the differential diagnosis of rhinorrhea in newborns.
Oxybutynin-Induced Heatstroke in an Elderly Patient
Authors: Adubofour Kwabena O , Kajiwara Grace T , Goldberg Charles M , King-Angell Joan L
Published: January 2017

OBJECTIVE:

To report an elderly patient with oxybutynin-induced heatstroke and to remind clinicians of the possibility of drugs as an etiology of hyperthermia.

CASE SUMMARY:

An elderly man was admitted to the emergency department in a confused state. The day of admission was the hottest of the summer months in the San Francisco area. Because his rectal temperature was 40 °C and his skin was hot and dry, he was immediately packed in ice, given intravenous NaCl 0.9%, and a cooling fan was used to aid in external cooling. The patient was taking oxybutynin chloride, a drug with anticholinergic properties. The previous summer he had been admitted with a rectal temperature of 41.1 °C. No infectious etiology could be found. He was discharged in an improved state after a 48-hour observation period. The drug was discontinued.

DISCUSSION:

It is important to recognize heatstroke and institute prompt management because of the high mortality associated with this thermoregulatory disorder. Prompt treatment should consist of rapid cooling and vigorous cardiopulmonary support.

CONCLUSIONS:

The possibility of drug-induced heatstroke should be investigated in all patients admitted during the summer months with unexplained hyperthermia, especially the elderly. To our knowledge this is the first reported case of heatstroke associated with the use of oxybutynin.
Depression in the Medically Ill Elderly: A Focus on Methylphenidate
Authors: Emptage Ruth E , Semla Todd P
Published: January 2017

OBJECTIVE:

To describe depression in the medically ill elderly and discuss methylphenidate as a treatment option.

DATA SOURCES:

A MEDLINE search from 1986 to 1995 was done to identify the literature published on depression in the medically ill as well as the literature on the use of methylphenidate for depression in the medically ill elderly. The references of articles found were evaluated for other relevant articles.

STUDY SELECTION:

Retrospective and prospective studies that evaluated the use of methylphenidate in depressed, medically ill elderly were reviewed.

DATA EXTRACTION:

Information on depression in the medically ill elderly was abstracted from original and review articles on the subject. The information pertaining to methylphenidate came from clinical studies.

CONCLUSIONS:

Depression in the medically ill elderly occurs frequently and is underdetected in part because of the difficulty in diagnosing depression in this population. Methylphenidate has been found to be a safe and effective treatment of depression in the medically ill elderly. A potential advantage of methylphenidate over other antidepressants is its relatively quick onset of action, usually within 2–5 days. Older patients whose depressive symptoms are interfering with their functional capabilities or participation in prescribed therapies to improve or restore function after a medical illness should be considered for a trial of methylphenidate.
Acute Dystonic Reaction to Methotrimeprazine in Hypoparathyroidism
Authors: Gur Hanan , Paz Yoav , Sidi Yechezkel
Published: January 2017

OBJECTTVE:

To report a case of acute dystonic reaction to methotrimeprazine in a patient with untreated hypoparathyroidism, emphasizing the potential increased sensitivity of hypocalcemic patients to the extrapyramidal adverse effects of antipsychotic drugs.

CASE SUMMARY:

An 80-year-old man who had untreated hypoparathyroidism and chronic hypocalcemia developed an acute dystonic reaction 20 minutes after ingestion of methotrimeprazine 25 mg. His medical history included an ill-defined psychiatric disorder for which he had been treated with methotrimeprazine several years earlier. The patient denied having any other diseases or taking any other medications. After 4 days, the disorientation, psychomotor restlessness, dystonic grimacing, protrusion of the tongue, and speech difficulties disappeared, despite a remaining low serum calcium concentration.

DISCUSSION:

A possible mechanism, by which striatal calmodulin-mediated adenylate cyclase activation is inhibited by the combined effects of phenothiazines and hypocalcemia, is discussed.

CONCLUSIONS:

In this patient, it is not possible to ascertain whether the dystonic reaction was due to hypocalcemia, phenothiazine administration, or both. However, it is suggested that patients with hypocalcemia may be sensitive to the extrapyramidal adverse effects of antipsychotics. In addition, acute unexpected dystonic reactions to a small dose of antipsychotics warrants measurement of the patient's serum calcium concentration.
The past as Prelude to the Future: History, Status, and Future of Antiviral Drugs
Authors: Whitley Richard J
Published: January 2017

OBJECTIVE:

To review the first generation of antiviral agents (e.g., idoxuridine, amantadine, vidarabine) that paralleled discovery of antineoplastic agents.

DATA SOURCES:

A MEDLINE search (1962 to 1996) of the English-language literature pertaining to antiviral agents was performed.

DATA EXTRACTION:

All articles were considered for this review. Pertinent references on antiviral therapy, as judged by the author, were selected.

DATA SYNTHESIS:

Acyclovir, the first second-generation antiviral agent, has a known selective mechanism of action and provides the model for development of future antiviral therapies. Despite the safety and clinical value of acyclovir, therapy does not prevent establishment of latency or decrease frequency of occurrences, resistance has been documented, and outcome is frequently poor. With the emergence of the HIV/AIDS epidemic, several antiretroviral agents have been developed and approved. However, none of the four available nucleoside analogs provides a cure.

CONCLUSIONS:

Viral resistance has emerged as an important component of antiviral therapy. Improved therapies for cytomegalovirus are needed. Several new therapies for herpes zoster, including prodrugs, are licensed or in Phase III clinical trials. Future directions include the use of molecular biologic techniques to identify enzymes unique to viral replication and to accelerate diagnosis of viral diseases.
Syncope: Pathophysiology, Diagnosis, and Pharmacotherapy
Authors: Lazarus Jodie C , Mauro Vincent F
Published: January 2017

OBJECTIVE:

To review the pathophysiology, diagnosis, and pharmacotherapy of syncope, with emphasis placed on neurocardiogenic syncope.

DATA SOURCES:

A MEDLINE search (1980–1995) using the term syncope and cross-referencing selected articles.

STUDY SELECTION:

Articles selected were those considered to assist in providing the reader with a basic introduction to the pathophysiology, diagnosis, and pharmacotherapy of syncope, with emphasis placed on neurocardiogenic syncope.

DATA SYNTHESIS:

Syncope is a common disorder with many different etiologies. The patient's history and physical examination are extremely important in making the diagnosis. The recent availability of head-upright tilt testing and electrophysiologic studies of the myocardium have helped define the etiology in many patients in whom an etiology would not have been found in the past. When the cause of syncope has been diagnosed, the appropriate therapy to prevent future attacks will be defined in many instances. One form of syncope, known as neurocardiogenic syncope, can be difficult to treat. Recent trials have suggested the use of beta-blockers, fludrocortisone, disopyramide, or selective serotonin reuptake inhibitors may be helpful in some patients.
Agency for Health Care Policy and Research Clinical Practice Guidelines
Authors: Perfetto Eleanor M. , Morris Lisa Stockwell
Published: January 2017

OBJECTIVE:

To review and summarize past activities of guidelines development at the Agency for Health Care Policy and Research (AHCPR) to enhance understanding of its new role and facilitate the development of new guidelines.

DATA SYNTHESIS:

The current Congressional climate and past criticisms of the guidelines development process have caused the AHCPR to reevaluate the way it produces guidelines. This assessment has resulted in the AHCPR restructuring its role to serve now as a science partner with private and public organizations.

CONCLUSIONS:

The development and role of evidence-based clinical practice guidelines are discussed, and the new roles of the AHCPR are described.
Reliability of a Modified Medication Appropriateness Index in Ambulatory Older Persons
Authors: Fitzgerald Lynn S , Hanlon Joseph T , Shelton Penny S , Landsman Pamela B , Schmader Kenneth E , Pulliam Charles C , Williams Mark E
Published: January 2017

OBJECTIVE:

To evaluate the reliability of a medication appropriateness index (MAI) modified for elderly outpatients in a non-Veterans Affairs setting.

DESIGN:

Reliability study.

SETTING:

General community.

PARTICIPANTS:

Ten community-dwelling elderly (> 65 y) taking five or more regularly scheduled medications and participating in a university-based health service intervention study.

MAIN OUTCOME MEASURES:

Interrater reliability of MAI ratings of 65 medications made by two clinical pharmacists for individual items and for an overall summed score was calculated by use of κ statistics and intraclass correlation coefficient.

RESULTS:

The interrater agreement for each of the individual MAI items was high for both appropriate and inappropriate ratings and ranged from 80% to 100% (overall κ = 0.64). Overall agreement for the summed score was good (intraclass correlation = 0.80).

CONCLUSIONS:

The modified MAI is a reliable instrument for evaluation of medication appropriateness in a non-Veterans Affairs, ambulatory, elderly population and may provide pharmacists with a practical and standard method to evaluate patients' drug regimens and identify some potential drug-related problems.
Nifedipine Interaction with Tacrolimus in Liver Transplant Recipients
Authors: Seifeldin Raafat A , Marcos-Alvarez Amadeo , Gordon Fredric D , Lewis W David , Jenkins Roger L
Published: January 2017

OBJECTIVE:

To examine the possible drug interaction between nifedipine and tacrolimus in liver transplant recipients.

STUDY DESIGN:

A retrospective study was done comparing two groups of liver transplant recipients. The starting time for comparison was the same after transplant. One group (n = 22) consisted of hypertensive patients who were treated with nifedipine; the other group (n = 28) did not receive nifedipine. The two groups were compared over 1 year. The effect of nifedipine on tacrolimus was measured in terms of tacrolimus whole blood trough concentrations, daily tacrolimus dosages, and cumulative tacrolimus dosages at 1, 3, 6, and 12 months. All patient charts were reviewed with regard to concurrent medication that could affect the metabolism of tacrolimus and eventually affect tacrolimus concentrations and dosages.

DATA COLLECTION:

All required information was retrieved from medical records.

RESULTS:

There was a statistically significant difference between daily dosage requirements of tacrolimus at 90 (p = 0.03), 180 (p = 0.004), and 365 (p = 0.0004) days between the nifedipine and no-nifedipine groups. The tacrolimus daily dosage in the nifedipine group was decreased by 26%, 29%, and 38% at 3, 6, and 12 months, respectively, compared with the dosage of the no-nifedipine group. Statistically significant differences in cumulative dosages of tacrolimus were observed at 180 (p = 0.02) and 365 (p = 0.003) days between the nifedipine and no-nifedipine groups, with cumulative dosage reduction of 25% and 31% by 6 and 12 months, respectively, in the nifedipine group compared with the no-nifedipine group.

CONCLUSIONS:

Nifedipine decreased the daily and cumulative dosage requirement of tacrolimus. The interaction observed between nifedipine and tacrolimus is the first reported in humans and is clinically important. As a result of this drug interaction, it is recommended that blood concentrations of tacrolimus be monitored during coadministration of these drugs and that the tacrolimus dosage be adjusted accordingly.
Spironolactone-Induced Agranulocytosis
Authors: Whitling Anna M , Pérgola Pablo E , Sang John Lee , Talbert Robert L
Published: January 2017

OBJECTIVE:

TO report a case of agranulocytosis secondary to spironolactone in a patient with cryptogenic liver disease.

CASE SUMMARY:

A 58-year-old Hispanic woman with cryptogenic cirrhosis was admitted to University Hospital on October 31, 1995. Laboratory data revealed a leukocyte count of 1.0 × 103/mm3 and an absolute neutrophil count (ANC) of 10 cells/mm3. Prior to treatment with spironolactone, the leukocyte count was 10.2 × 103/mm3 and ANC 8400 cells/mm3. Agranulocytosis resolved 5 days following the discontinuation of spironolactone. Results from the bone marrow biopsies before and after treatment with spironolactone suggested that agranulocytosis was caused by the drug's toxic effect on the bone marrow.

DISCUSSION:

Drug-induced agranulocytosis is a serious adverse effect, occurring at a rate of approximately 6.2 cases per million persons each year. In addition to the case reported here, three other reports of agranulocytosis secondary to spironolactone have been published in the literature. Several factors have been identified that may increase a patient's risk for developing agranulocytosis, including increased age, hepatic or renal impairment, drag dosage and duration, and concurrent medications.

CONCLUSIONS:

Agranulocytosis secondary to spironolactone is a serious potential adverse effect. Patients with risk factors for developing this adverse effect should be closely monitored since early detection and discontinuation of spironolactone can improve prognosis.
Pegaspargase: An Alternative?
Authors: Holle Lisa M
Published: January 2017

OBJECTIVE:

TO review the chemistry, pharmacology, pharmacokinetics, clinical activity, adverse effects, dosage, and administration guidelines for pegaspargase.

DATA SOURCES:

A MEDLINE search (1980–1996), a CANCERLIT search (1983–1996), and a CURRENT CONTENTS search (1980–1996) using the terms pegaspargase, PEG-asparaginase, PEG-L-asparaginase, polyethylene glycol L-asparaginase, polyethylene glycol conjugated L-asparaginase, and Oncaspar were conducted.

STUDY SELECTION AND DATA EXTRACTION:

All articles were considered for possible inclusion in this review. Abstracts were included only when they were judged to add critical information not otherwise available in the medical literature.

DATA SYNTHESIS:

L-Asparaginase has been a main component of treatment regimens for acute lymphocytic leukemia. A key limiting factor of L-asparaginase use has been the development of hypersensitivity to the drug. Recently, a polyethylene glycol (PEG) conjugated form of L-asparaginase, pegaspargase, has been made available. PEG modification of L-asparaginase has been shown to alter the tendency of the enzyme to induce an immune response and to extend the half-life of the drug. The majority of patients with hypersensitivity to the native enzyme preparations tolerate pegaspargase without further clinical hypersensitivity. The adverse effect profile of pegaspargase is similar to that of the native forms of L-asparaginase. The recommended dosage of pegaspargase is 2500 IU/m2 administered by intramuscular or intravenous injection every 2 weeks in combination with other chemotherapeutic agents.

CONCLUSIONS:

Pegaspargase is a safe, effective alternative to L-asparaginase in patients who have had clinical hypersensitivity reactions to both Escherichia coli- and Erwinia carotovora-demed L-asparaginase. However, pegaspargase should not be routinely substituted for L-asparaginase.
Implementation of Pharmaceutical Care Services for Patients with Hyperlipidemias by Independent Community Pharmacy Practitioners
Authors: Shibley Michelle CH , Pugh Carol B
Published: January 2017

OBJECTIVE:

To implement and evaluate pharmaceutical care services for patients with hyperlipidemias in the community pharmacy setting, to evaluate the results of a pharmaceutical care training process for pharmacists by using an assessment quiz, and to measure patient outcomes resulting from provision of pharmaceutical care to patients with hyperlipidemia.

DESIGN:

A prospective study was conducted over a 1 -year period. Patients served as their own controls.

SETTING:

Two independent community pharmacies in Richmond, Virginia.

PARTICIPANTS:

Twenty-five adult patients with confirmed dyslipidemias completed the study.

INTERVENTIONS:

Study pharmacists assessed each patient and assisted in setting therapeutic goals; patients also completed a visit with a registered dietitian. Drug therapy recommendations were made to physicians by the pharmacist when appropriate. Follow-up was scheduled with the pharmacist to ensure positive outcomes and reduce adverse effects.

MAIN OUTCOME MEASURES:

Fasting lipoprotein profiles were measured initially and at 6 and 12 months. The SF-36 survey, the MacKeigan-Larson satisfaction survey, and a patient opinion survey were administered initially and at the conclusion of the study.

RESULTS:

Total cholesterol and low-density lipoprotein cholesterol values were significantly decreased at 12 months compared with either the baseline or 6-month values (p < 0.02). Significant improvement was found in several domains of the surveys; quality of life, patient satisfaction with pharmacy services, and patient opinions on the role of the pharmacist improved after the intervention.

CONCLUSIONS:

Pharmaceutical care may positively affect lipid values, quality of life, and patient satisfaction.
Suspected Lamotrigine-Induced Toxic Epidermal Necrolysis
Authors: Chaffin Julie J , Davis Steven M
Published: January 2017

OBJECTIVE:

To describe a patient who developed toxic epidermal necrolysis (TEN) possibly secondary to lamotrigine use.

CASE SUMMARY:

A 74-year-old white man with a history of probable complex partial seizures was admitted to the neurology service for a prolonged postictal state. His antiepileptic regimen was changed while he was in the hospital to include lamotrigine. After 19 days of hospitalization and 14 days of lamotrigine therapy, the patient became febrile. The next day he developed a rash which progressed within 4 days to TEN, diagnosed by skin biopsy. All suspected drugs were discontinued, including lamotrigine. The patient was treated with hydrotherapy in the burn unit. His symptoms improved and he was discharged from the hospital 26 days after the rash developed.

DISCUSSION:

During lamotrigine's premarketing clinical trials, the manufacturer reported several cases of Stevens-Johnson syndrome and TEN. There are several published case reports of lamotrigine-induced severe skin reactions. All of these reports included patients being treated with both valproic acid and lamotrigine. Our patient was exposed to phenytoin, carbamazepine, clindamycin, and lamotrigine, but not valproic acid. The patient reported prior use of phenytoin with no skin rash. Carbamazepine was the antiepileptic drug the patient was maintained on prior to his hospital admission, and the symptoms of TEN resolved while he was still receiving carbamazepine. The patient received only two doses of clindamycin, which makes this agent an unlikely cause of TEN.

CONCLUSIONS:

Because of the temporal relationship of the onset of the patient's rash and several drugs that are known to cause severe rashes, it is not certain which drug was the definite culprit. However, based on the evidence from the literature, lamotrigine appears to be the causative agent.
Controversies Surrounding Estrogen Use in Postmenopausal Women
Authors: Witt Daniel M , Lousberg Tammy R
Published: January 2017

OBJECTIVE:

To provide an overview of controversies regarding the use of estrogen in postmenopausal women.

DATA SOURCES:

A MEDLINE search was conducted to identify pertinent literature published since 1990. Recently published textbooks devoted to the subjects of menopause and women's health were also reviewed, particularly their bibliographies. The bibliographies of selected review articles were also reviewed.

STUDY SELECTION:

Due to the vast amount of literature, only the most relevant published studies were reviewed. Review articles and book chapters authored by researchers of international reputation were also reviewed.

DATA EXTRACTION:

Identified studies from the primary literature and selected reviews were carefully reviewed. Information regarding the use of estrogen in postmenopausal women was extracted. Particular attention was given to areas of controversy commonly dealt with in the lay media.

DATA SYNTHESIS:

The number of postmenopausal women in the US will approach 60 million in the next decade. Despite numerous potential benefits, many women elect to not take estrogen due to fear of cancer or poor understanding of the long-term consequences of menopause and the beneficial effects of estrogen replacement therapy. Many women rely on the news media for information about hormone therapy and subsequently become confused regarding the benefits and risks. Estrogen relieves climacteric symptoms such as hot flushes and symptoms related to genitourinary tissue atrophy. Outcomes from controlled clinical trials are lacking, but numerous epidemiologic studies document clinically significant decreases in cardiovascular disease and osteoporotic morbidity and mortality. Unopposed estrogen increases the risk for endometrial cancer, but addition of a progestin for at least 10 days per cycle effectively reduces this risk to that of women who do not take estrogen. The association between postmenopausal estrogen use and breast cancer remains controversial, despite the results of numerous observational studies. This uncertainty regarding estrogen replacement and breast cancer risk can actually be reassuring when placed in proper perspective.
Phenolphthalein-Induced Toxic Epidermal Necrolysis
Authors: Artymowicz Richard J , Childs Arthur L , Paolini Lawrence
Published: January 2017

OBJECTIVE:

To report a case of phenolphthalein-induced toxic epidermal necrolysis (TEN) in a patient maintained on several other medications more commonly known to be associated with TEN.

CASE SUMMARY:

A 78-year-old white man presented with intractable lower back pain and constipation. On day 1 of admission, the patient exhibited a diffuse urticarial rash over his trunk and extremities. History revealed that the patient had taken a combination phenolphthalein/docusate sodium (Correctol) over-the-counter laxative 1 day prior to admission. He had a similar urticarial rash 1.5 years earlier with this product and was instructed not to use it. A biopsy was performed and evidence from light microscopic analysis of the tissue led to a diagnosis of TEN. Furosemide, spironolactone, allopurinol, and hydroxyurea were considered possible causes of the reaction and were discontinued. Despite this, the lesions worsened in severity. The patient subsequently responded well to intravenous antibiotics, intravenous corticosteroids, and local wound care. Furosemide, spironolactone, hydroxyurea, allopurinol, and docusate were all reintroduced without reactivation of the lesions.

DISCUSSION:

phenolphthalein is the active ingredient in several over-the-counter laxative preparations and has only rarely been reported to cause TEN. (It is no longer contained in Correctol.) To our knowledge, this case report represents only the third description of laxative-induced TEN. Although this patient had been exposed to several other medications more commonly associated with TEN, his long-term tolerance of and uneventful rechallenge with these medications exclude them as potential catalysts to this drug reaction. The patient's previous rash and the temporal relation of this event and the ingestion of phenolphthalein, as well as the similarity of this case to other reports, point to phenolphthalein as the cause of TEN in this patient.

CONCLUSIONS:

TEN is a rare disorder that can be fatal in up to 30% of patients. Clinicians should include phenolphthalein in their list of possible causes of drug-induced TEN. A careful and complete medication history can help avoid unnecessary discontinuation of clinically important medications and inadvertent rechallenge with the causative agent.
Amphotericin B Lipid Complex
Authors: Rapp Robert P , Gubbins Paul O , Evans Martin E
Published: January 2017

OBJECTIVE:

To evaluate the published data on the effectiveness and safety of amphotericin B lipid complex (ABLC) for the treatment of invasive mycosis and to evaluate data describing the pharmacologic properties and pharmacokinetic behavior of ABLC in both animals and humans.

DATA SOURCE:

A MEDLINE search was conducted to identify literature published from 1965 to January 1997 for amphotericin B deoxycholate (DCAB) and ABLC. In addition, preliminary data published as abstracts and presented at national conferences on infectious disease and hematology within the last 6 years were also included in this review.

STUDY SELECTION:

Both human and animal studies were reviewed. Animal and in vitro studies were selected to evaluate the pharmacologic and toxicologic properties of ABLC. For the evaluation of the efficacy, safety, and pharmacokinetic behavior of ABLC, large, well-controlled studies were reviewed. In addition, data from open-label and emergency use protocols were also included in the review.

DATA EXTRACTION:

The study and analytical methods, results, and conclusions of the selected studies were evaluated. Pharmacokinetic data for both ABLC and DCAB that were derived from human subjects were also evaluated.

DATA SYNTHESIS:

DCAB has been the cornerstone for the treatment of invasive mycosis, even though it has a narrow therapeutic index. Infusion-related toxicities (e.g., fever, chills, rigors) are likely due to DCAB stimulation of cytokine and prostaglandin synthesis. Conversely, nephrotoxicity, the primary non-infusion-related toxicity, likely results from the nonselective cytotoxic interaction between DCAB and cholesterol-containing mammalian cells. ABLC represents a new approach to improving the therapeutic index of DCAB. Mammalian cytotoxicity is attenuated by complexing amphotericin B to a mixture of phospholipids. This alters the affinity of amphotericin B and decreases its selective transfer from the complex to cholesterol-containing mammalian cells. Fungi also possess lipase, which improves the selective transfer from the complex to ergosterol-containing cell membranes. In humans, the lipid formulation increases the volume of distribution of amphotericin B. Thus, compared with DCAB, larger doses of ABLC can be administered for a longer duration with less nephrotoxicity. However, the prevalence of infusion-related toxicities associated with ABLC is similar to that of DCAB. Whether the alteration in distribution improves efficacy by improving tissue concentrations of amphotericin B has not been determined. The cost of this agent will limit its use.

CONCLUSIONS:

ABLC has been shown to be at least as effective as DCAB, and it has been well tolerated in the clinical studies to date. Despite large dosages and extended courses of administration, there is little nephrotoxicity associated with its use. However, the cost of this agent will limit its use to the treatment of refractory mycosis or to cases where DCAB is contraindicated due to significant renal insufficiency.
Compatibility and Stability of Paclitaxel Combined with Cisplatin and with Carboplatin in Infusion Solutions
Authors: Zhang Yanping , Xu Quanyun A , Trissel Lawrence A , Gilbert Doward L , Martinez J Frank
Published: January 2017

OBJECTIVE:

To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 0.3 and 1.2 mg/mL with cisplatin 0.2 mg/mL in NaCl 0.9% injection and with carboplatin 2 mg/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32°C.

DESIGN:

The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at temperatures of 4, 23, and 32°C for physical and chemical stability. Physical stability was assessed by using visual observation in normal light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the three drugs was evaluated by using three stability-indicating HPLC analytical techniques.

RESULTS:

All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred in 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained above 90% in all samples throughout the study. Cisplatin admixtures exhibited paclitaxel concentration-dependent decomposition with cisplatin losses of approximately 5–8% in 4 hours and approximately 20% in 1 day at 23 and 32°C in the paclitaxel 1.2 mg/mL admixtures. With paclitaxel 0.3 mg/mL in the admixtures, cisplatin losses were about 10% in 7 days at these temperatures. Carboplatin in admixtures with both concentrations of paclitaxel was stable for 7 days at 4°C, but sustained losses of about 10% and 12% in 3 days at 23 and 32°C, respectively.

CONCLUSIONS:

Admixtures of paclitaxel 0.3 and 1.2 mg/mL with cisplatin and carboplatin are limited in their utility time by both paclitaxel microcrystalline precipitation and decomposition of cisplatin and carboplatin. The admixture of paclitaxel 1.2 mg/mL with cisplatin 0.2 mg/mL in NaCl 0.9% injection exhibits unacceptable cisplatin loss in 24 hours. All other combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32°C.
Routine Monitoring of Gentamicin Serum Concentrations in Pediatric Patients with Normal Renal Function is Unnecessary
Authors: Logsdon Beth A , Phelps Stephanie J
Published: January 2017

OBJECTIVE:

Due to increasing demands for cost containment within the healthcare system, we evaluated the need for routine gentamicin concentrations (i.e., peak and trough with third dose).

DESIGN:

Single-institution study performed concurrently with hospitalization.

SETTING:

A 225-bed pediatric teaching hospital.

PARTICIPANTS:

The study population consisted of 150 hospitalized pediatric patients (53% medicine, 47% surgical patients) from 3 months to 15 years old with normal serum creatinine.

OUTCOME MEASURES:

If the administered dose produced diagnoses-appropriate peak concentrations of at least 4 μg/mL or 5 μg/mL in bacteremia/septicemia and at least 6 μg/mL or 8 μg/mL in patients with pneumonia if trough serum gentamicin concentrations were less than 2 μg/mL, if the patient was noted by the attending physician to be clinically responding as well as objectively having a decreased white blood cell count and was afebrile, and if there was not an increase of 0.5 mg/dL or more in serum creatinine during the course of therapy.

RESULTS:

Patients received a mean dose of gentamicin 2.51 ± 0.14 mg/kg iv q8h, which resulted in a mean peak concentration of 6.1 ± 1.7 μg/mL (range 2.4–11.7) and a mean trough concentration of 0.5 ± 0.3 μg/mL (range 0.1–1.8). Peak and trough concentrations were at least 4 μg/mL and less than 2 μg/mL in 96% and 100% of patients, respectively. No patient required a dosage change due to lack of clinical response.

CONCLUSIONS:

Our data do not support the routine monitoring of gentamicin concentrations in pediatric patients older than 3 months of age who are receiving appropriate standard doses of gentamicin and have normal renal function.
The Reliability and Validity of a First Ray Measurement Device
Authors: Glasoe Ward Mylo , Yack John , Saltzman Charles L.
Published: January 2017

The need for measuring the mobility of the first ray has been identified. The purpose of this study was to test the reliability and validity of a device built to measure the relative vertical displacement of the first ray. Twenty fresh frozen cadaver feet were sampled (mean age of donor was 70 ± 13 years). Dorsal mobility of the first ray was measured by device over three trials of repeated loading using 20 N, 35 N, 55 N and 85 N of force. Radiographs served as the criterion standard for validation of the device. Vertical displacement was measured from x-ray by a digitizing procedure that recorded movement of the first ray during loading. Reliability of the device assessed by intraclass correlation coefficients (ICC) was .98 with standard errors of the measurement calculated to be 0.35 mm. A correlation of agreement value of .97 was determined for the two methods of measurement. Analysis of variance testing found a significant interaction between force and method of measurement. Tukey post-hoc analysis found no difference (F < 1.70) between the two methods of measuring first ray displacement in cadaver specimens when the force applied did not exceed 55 N. At 85 N of force (F = 10.05), unwanted movement of the second metatarsal caused the device to overestimate the amount of displacement that occurred specific to the first ray. This measure of first ray mobility should help clinicians and researchers to better investigate foot pathology resulting from faulty mechanics of the first ray.
Specialty Day of the European Foot and Ankle Society (EFAS), June 6, 1999 at the 4th Congress of the European Federation of National Associations of Orthopaedics and Traumatology (EFORT)
Authors: Wüelker Nikolaus
Published: January 2017

Specialty Day of the European Foot and Ankle Society (EFAS) June 6, 1999, at the 4th Congress of the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) from June 3–8 in Brussels, Belgium.
Influence of the Interosseous Talocalcaneal Ligament Injury on Stability of the Ankle-Subtalar Joint Complex — a Cadaveric Experimental Study
Authors: Tochigi Yuki , Takahashi Kazuhisa , Yamagata Masatsune , Tamaki Tamotsu
Published: January 2017

The present study aims to clarify the influence of the interosseous talocalcaneal ligament (ITCL) injury associated with injury to the lateral ankle ligaments on the ankle-subtalar joint complex motion under conditions of physiologic loading. We conducted mechanical tests using five fresh cadaveric lower extremities. Each specimen was mounted in the loading device and an axial cyclic load from 9.8 to 686 N was applied. Three-dimensional rotations of the ankle and the subtalar joint were measured simultaneously by a linkage electric goniometer. Mechanical tests were repeated after sectioning of the anterior talofibular ligament (ATFL), and again after additional sectioning of the ITCL.

In the intact condition, the ankle and the subtalar joints rotated consistently with increase of the load. The predominant rotations were plantar flexion and adduction at the ankle joint, with some eversion demonstrated at the subtalar joint. Although ATFL sectioning did not significantly change the motion of the two joints, additional sectioning of the ITCL significantly increased adduction and total rotation of the ankle joint. The present study demonstrated that a combined injury of the ATFL and the ITCL can induce anterolateral rotatory instability of the ankle joint under conditions of axial loading.
Sensory Thresholds of Normal Human Feet
Authors: Jeng Clifford , Michelson James , Mizel Mark
Published: January 2017

Hypotheses/Purpose:

Although several studies in the literature have evaluated the abnormal sensory thresholds of diabetic feet to Semmes-Weinstein monofilament testing, there is very limited data on the sensory thresholds of individuals without diabetes or peripheral neuropathy. The purpose of this study was to assess the dorsal and plantar sensation of the feet from 40 healthy, college-aged volunteers using Semmes-Weinstein monofilaments. Conclusions/Significance: Semmes-Weinstein testing is a useful tool in predicting which diabetic patients may be at risk for ulceration of the feet. Several studies have determined 5.07 to be the threshold for protective sensation. Based on the normal values derived in this study, the inability to feel a Semmes-Weinstein monofilament of 5.07 (as in diabetic neuropathy) represents a sensory threshold that is more than 50 times greater than normal. This means that roughly 98% of the sensory ability has been lost.

Methods:

20 male and 20 female volunteers between the ages of 18 to 22 years old were selected. None had a history of any significant injury or previous surgery to the foot or ankle. There were no known medical conditions associated with decreased foot sensation, (e.g.- diabetes, syphilis, leprosy, myelomeningocele, syringomyelia, or hereditary neuropathy). Volunteers were also questioned regarding participation in athletic activities. The subjects were blindfolded with the leg resting comfortably on a chair as 14 plantar and 5 dorsal locations were tested on each foot. The right foot was always tested first. Each site on the foot had the Semmes-Weinstein monofilaments applied to it first, in an order of increasing stiffness, then repeated in decreasing order, using all twenty monofilaments in the set. A positive threshold response was recorded when the subject could feel the filament and could accurately locate where on the foot the stimulus had been applied. The left foot was then tested in an identical fashion.

Results:

The mean sensitivity for all sites was 3.63 (0.0075 SEM). There were significant differences between sites, between using increasing or decreasing monofilament stiffness, between subjects, and in some instances, between right foot and left foot values. When testing was performed from the higher to lower monofilament stiffness, subjects were found to have significantly better sensitivity, which indicates the importance of a consistent testing protocol (either all up or all down). Sensation in the lesser toes and the arch were the most sensitive followed by the hallux and the plantar metatarsal heads. The least sensitive site was the heel, with 1/6th the sensitivity of the most sensitive toes.